The biochemistry of aging and longevity encompasses a broad range of molecular, cellular, and physiological processes that contribute to the progression of aging and determine lifespan. Understanding these mechanisms is crucial for developing interventions to promote healthy aging and potentially extend lifespan. This article is an attempt to outline the key biochemical pathways and mechanisms involved in aging and longevity, and to discuss how the approach of MIT homeopathy and molecular imprinted drugs could be utilized in the management of geriatric health problems and to attain longevity.
Oxidative stress arises when there’s an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defenses of the cell. ROS are by-products of normal cellular metabolism, primarily generated in mitochondria. Over time, excessive ROS can damage DNA, proteins, and lipids, contributing to aging and age-related diseases. Antioxidant enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase play critical roles in neutralizing ROS, protecting cells from oxidative damage.
Telomeres are protective caps at the ends of chromosomes that shorten with each cell division. Once telomeres reach a critically short length, cells enter a state of replicative senescence or apoptosis, contributing to aging. The enzyme telomerase can elongate telomeres, promoting cellular longevity. However, telomerase activity is tightly regulated and is often repressed in somatic cells, making telomere maintenance a key focus in the study of aging and longevity.
Genomic instability, including DNA damage and mutation accumulation, is a hallmark of aging. Various endogenous and exogenous factors can induce DNA damage, while diminished DNA repair capabilities exacerbate the issue with age. The maintenance of genomic integrity, through mechanisms such as nucleotide excision repair, base excision repair, and DNA damage response pathways, is crucial for longevity.
Proteostasis involves the balance between protein synthesis, folding, trafficking, and degradation. Disruption in proteostasis, leading to the accumulation of misfolded or aggregated proteins, is associated with aging and many age-related diseases. Molecular chaperones and proteasomal and autophagic degradation pathways are vital for maintaining proteostasis.
Nutrient sensing pathways, including the insulin/IGF-1 signaling (IIS), mTOR, AMPK, and sirtuins, play significant roles in regulating metabolism, growth, and aging. Caloric restriction and interventions that modulate these pathways have been shown to extend lifespan in various model organisms. These pathways modulate an array of processes, from energy metabolism to stress resistance and autophagy, influencing the aging process.
Cellular senescence is a state of permanent cell cycle arrest induced by various stressors, including telomere shortening, DNA damage, and oncogene activation. Senescent cells accumulate with age and secrete pro-inflammatory factors (the senescence-associated secretory phenotype, or SASP), contributing to tissue dysfunction and age-related pathologies. Clearing senescent cells or modulating the SASP holds promise for mitigating aging effects.
Research in biochemistry of aging and longevity is rapidly advancing, with emerging areas such as epigenetic alterations, stem cell exhaustion, and intercellular communication gaining attention. Interventions like senolytics, NAD+ boosters, and rapamycin analogs are being explored for their potential to delay aging and extend healthy lifespan. Understanding the intricate web of biochemical pathways that contribute to aging and longevity is essential for developing effective strategies to enhance healthspan and potentially extend lifespan.
ROLE OF PROTEIN INHIBITIONS AND PROTEIN DEFORMATIONS
The role of protein inhibitions in the aging process encompasses a range of mechanisms that disrupt the balance of protein synthesis, folding, and degradation, collectively known as proteostasis. This disruption leads to the accumulation of misfolded or aggregated proteins, which is a hallmark of aging and is implicated in the onset and progression of age-related diseases. Here, we delve into several key areas where protein inhibition plays a significant role in the aging process:
Autophagy is a cellular process that degrades and recycles damaged organelles and proteins. With age, the efficiency of autophagy declines, leading to the accumulation of damaged proteins and organelles, contributing to cellular aging and dysfunction.
Proteasomal degradation involves the breakdown of proteins tagged with ubiquitin. Age-related decline in proteasome activity results in reduced protein degradation capacity, contributing to the buildup of damaged and misfolded proteins.S
Proteins with altered structures can form aggregates that are toxic to cells. Diseases such as Alzheimer’s (characterized by amyloid-beta and tau protein aggregates) and Parkinson’s (characterized by alpha-synuclein aggregates) exemplify how protein aggregation can lead to cellular dysfunction and disease. The age-related increase in protein aggregation contributes to the decline in cellular function and organismal aging.
Molecular chaperones assist in protein folding and prevent the aggregation of misfolded proteins. With aging, the expression levels and activity of chaperones decrease, impairing their protective role and allowing increased accumulation of misfolded proteins. This exacerbates cellular stress and contributes to the aging process.
Several signaling pathways that regulate protein synthesis and degradation are altered with aging, including the mTOR pathway and insulin/IGF-1 signaling pathway. Dysregulation of these pathways affects protein homeostasis, leading to increased susceptibility to stress and aging.
Chronic low-grade inflammation and oxidative stress are characteristic of aging and can directly inhibit the function of proteins through oxidative modifications. These modifications can alter protein structure and function, leading to a further decline in proteostasis and exacerbating the aging process.
Understanding the role of protein inhibitions in aging has led to the exploration of interventions aimed at restoring proteostasis, including:
Enhancement of autophagy and proteasomal activity through pharmacological agents or dietary interventions like caloric restriction.
Use of molecular chaperones as therapeutic agents to assist in the proper folding of proteins and prevent aggregation.
Modulation of signaling pathways (e.g., mTOR inhibitors like rapamycin) to restore balance in protein synthesis and degradation.
Antioxidants and anti-inflammatory compounds to mitigate oxidative stress and inflammation, thereby preserving protein function.
In summary, protein inhibition plays a crucial role in the aging process by disrupting proteostasis, leading to cellular dysfunction and the development of age-related diseases. Targeting the mechanisms underlying protein inhibition offers promising avenues for interventions aimed at promoting healthy aging and longevity.
ROLE OF ANTIBODIES IN AGEING PROCESS
Antibodies play a pivotal role in the immune system by recognizing and binding to specific antigens, such as pathogens or foreign substances, facilitating their neutralization or destruction. However, in the context of protein inhibitions, antibodies can also recognize and bind to specific proteins within the body, affecting their function in several ways. This interaction between antibodies and proteins is crucial in both therapeutic interventions and the pathogenesis of certain diseases.
Therapeutic antibodies can be designed to target and neutralize pathogenic proteins, such as toxins or proteins that viruses use to enter host cells. For example, antibodies against the spike protein of SARS-CoV-2 can prevent the virus from infecting cells.
In conditions characterized by the accumulation of misfolded proteins, such as Alzheimer’s disease, antibodies can be engineered to recognize and promote the clearance of these proteins. This approach aims to reduce the toxic effects of protein aggregates on cell function.
Certain therapeutic antibodies can inhibit the action of immune system proteins that promote inflammation and autoimmune responses. For instance, antibodies targeting tumor necrosis factor-alpha (TNF-α) are used in treating autoimmune diseases like rheumatoid arthritis, by reducing inflammation and tissue damage.
In autoimmune conditions, the body produces autoantibodies that mistakenly target and inhibit the function of its own proteins. This can lead to a wide range of dysfunctions depending on the proteins targeted. For example, in myasthenia gravis, autoantibodies bind to acetylcholine receptors at the neuromuscular junction, impairing muscle contraction.
Autoantibodies can directly inhibit the function of essential proteins by binding to active sites or regions critical for their activity. This can disrupt normal physiological processes and lead to disease symptoms.
Antibodies bound to circulating proteins can form immune complexes that deposit in tissues, leading to inflammation and tissue damage, as seen in conditions like systemic lupus erythematosus (SLE).
Antibodies can influence protein function significantly, serving both as essential tools for therapeutic intervention and diagnostics and as key players in the pathogenesis of various diseases. Understanding the interactions between antibodies and proteins is critical for developing new therapies and for the diagnosis and treatment of diseases.
ROLE OF PHYTOCHEMICALS IN AGEING
Phytochemicals are bioactive compounds found in plants that have various effects on human health, including antioxidant, anti-inflammatory, and anticarcinogenic properties. In the context of protein inhibition, phytochemicals can modulate protein function in several key ways, offering potential therapeutic benefits for a range of diseases, including cancer, neurodegenerative disorders, and cardiovascular diseases. Here, we explore the role of phytochemicals in protein inhibition, highlighting their mechanisms of action and implications for health and disease.
Many phytochemicals possess strong antioxidant properties, enabling them to neutralize reactive oxygen species (ROS) and reduce oxidative stress. Oxidative stress can lead to the oxidative modification of proteins, impairing their function and contributing to the pathogenesis of various diseases. By inhibiting oxidative stress, phytochemicals help maintain protein integrity and function.
Flavonoids, found in fruits, vegetables, tea, and wine, can directly scavenge ROS and upregulate antioxidant defense enzymes, thereby protecting proteins from oxidative damage.
Certain phytochemicals can directly inhibit the activity of specific enzymes involved in disease processes. This inhibition can modulate signaling pathways, metabolism, and the progression of diseases. Curcumin, a compound found in turmeric, can inhibit the activity of cyclooxygenase-2 (COX-2), an enzyme involved in inflammation, potentially offering benefits in conditions like arthritis and cancer.
Phytochemicals can also interfere with the aggregation of misfolded proteins, a feature common in neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease. By inhibiting protein aggregation, these compounds can potentially slow the progression of these conditions.
Epigallocatechin gallate (EGCG), a polyphenol in green tea, has been shown to inhibit the aggregation of beta-amyloid peptides in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease.
Phytochemicals can influence the expression levels of various proteins, including those involved in cell cycle regulation, apoptosis, and detoxification, through their actions on transcription factors and signaling pathways. Sulforaphane, found in cruciferous vegetables like broccoli, can activate the Nrf2 pathway, leading to the increased expression of detoxifying and antioxidant enzymes.
Some phytochemicals can bind to cellular receptors or signaling molecules, altering signal transduction pathways and affecting cell growth, apoptosis, and differentiation. Genistein, an isoflavone from soy, can bind to estrogen receptors, modulating the effects of estrogen on target tissues and potentially offering benefits in hormone-related cancers.
The role of phytochemicals in protein inhibition has significant implications for the prevention and treatment of diseases. Their natural origin and wide range of bioactivities make them attractive candidates for developing new therapeutic agents. However, more research is needed to fully understand their mechanisms of action, optimal doses, bioavailability, and potential side effects. Clinical trials are essential to confirm the health benefits of phytochemicals and to develop guidelines for their use in disease prevention and therapy.
ROLE OF ELEMENTAL CHEMICALS IN AGEING
Elemental chemicals, particularly metals, can play a significant role in protein inhibition, contributing to the aging process and the development of age-related diseases. While some metals are essential for life, acting as cofactors for various enzymes and playing roles in numerous biochemical pathways, others can be toxic, especially at high concentrations. Their interaction with proteins can lead to alterations in protein structure and function, oxidative stress, and disruption of cellular homeostasis, all of which are implicated in aging and its associated diseases.
Iron is essential for many biological processes, including oxygen transport and DNA synthesis. However, excessive iron can catalyze the formation of highly reactive hydroxyl radicals through the Fenton reaction, leading to oxidative damage to proteins, lipids, and DNA. This oxidative stress is a significant contributor to the aging process and the development of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, where iron accumulation in the brain has been observed.
Copper is another essential metal that serves as a cofactor for enzymes involved in energy production, antioxidant defenses, and neurotransmitter synthesis. However, like iron, excessive copper can contribute to oxidative stress by generating reactive oxygen species (ROS). Copper imbalance has been linked to neurodegenerative diseases and is known to catalyze the formation of toxic aggregates of proteins, such as beta-amyloid in Alzheimer’s disease.
Zinc is crucial for immune function, antioxidant defense, and DNA repair. It can also inhibit the aggregation of amyloid-beta peptides in vitro, suggesting a protective role in Alzheimer’s disease. However, dysregulation in zinc homeostasis can disrupt cellular functions and contribute to the aging process. For example, high concentrations of zinc can interfere with the function of various signaling proteins and enzymes.
Lead and mercury are toxic metals with no known essential biological function. Exposure to these metals can inhibit the activity of enzymes and disrupt protein function through the displacement of essential metals from their binding sites or direct interaction with thiol groups in proteins. This can lead to cellular toxicity, oxidative stress, and inflammation, contributing to the aging process and increasing the risk of age-related diseases.
Aluminum exposure has been suggested to play a role in the aging process and neurodegeneration, although the evidence is controversial. Aluminum can compete with essential metals for binding sites on proteins and enzymes, potentially altering their structure and function. It may also induce oxidative stress and inflammation, contributing to cellular aging.
Given the role of elemental chemicals in protein inhibition and the aging process, strategies to mitigate their effects include: Maintaining a balanced intake of essential metals through diet and possibly using specific chelators to reduce the bioavailability of toxic metals. Using antioxidants to counteract the oxidative stress induced by metal imbalance. Minimizing exposure to toxic metals through environmental regulations and personal protective measures.
Understanding the complex interplay between elemental chemicals and protein function is critical for developing strategies to mitigate their contributions to the aging process and to promote healthy aging.
ROLE OF ENDOGENOUS LIGANDS IN AGEING
Endogenous ligands, which include hormones, neurotransmitters, and other naturally occurring molecules within the body, can modulate protein activity through various mechanisms. Their role in protein inhibition can significantly impact cellular function and contribute to the aging process, affecting longevity, cellular senescence, and the development of age-related diseases. Here, we explore how endogenous ligands influence protein inhibition and its implications for aging.
Insulin and IGF-1 (Insulin-like Growth Factor-1): Elevated levels of insulin and IGF-1 can accelerate aging through the promotion of anabolic processes, including cell growth and proliferation. These hormones activate the insulin/IGF-1 signaling pathway, which has been implicated in the aging process. Inhibition of this pathway, through reduced levels of these ligands, has been shown to extend lifespan in various organisms by enhancing stress resistance and promoting metabolic efficiency.
This stress hormone cortisol can inhibit protein synthesis and increase protein degradation, contributing to muscle wasting and other age-related declines in tissue function. Chronic elevation of cortisol, often resulting from prolonged stress, can accelerate aging processes by promoting oxidative stress, inflammation, and cellular senescence.
The neurotransmitter Acetylcholine plays a crucial role in muscle function and cognitive processes. Its decline is associated with aging, particularly in conditions like Alzheimer’s disease, where acetylcholine-producing neurons deteriorate. Enhancing acetylcholine levels or activity, through inhibition of the enzyme acetylcholinesterase which breaks down acetylcholine, is a strategy used in the treatment of Alzheimer’s disease to improve cognitive function.
Dopamine levels decrease with age, impacting movement control and potentially contributing to the development of Parkinson’s disease. The inhibition of dopamine reuptake or degradation to increase its availability is a common therapeutic approach in managing Parkinson’s disease symptoms.
Although not ligands in the classical sense, Reactive Oxygen Species or ROS can act as signalling molecules that modulate protein function. Excessive ROS can inhibit the function of key cellular proteins through oxidative modifications, contributing to cellular aging and dysfunction. The body’s antioxidant defence mechanisms, which include endogenously produced molecules like glutathione, are crucial for counteracting ROS-mediated protein inhibition.
Nitric Oxide (NO) is a signaling molecule that influences various physiological processes, including vasodilation and neurotransmission. Dysregulation of NO production can contribute to vascular aging and neurodegeneration. In certain contexts, NO can inhibit mitochondrial function and enzyme activity, impacting cellular energy production and contributing to aging processes.
Targeting the interaction between endogenous ligands and proteins offers potential strategies for modulating the aging process. These include:
Lifestyle interventions, such as diet and exercise, to modulate hormone levels naturally.
Pharmacological agents that mimic, enhance, or inhibit the action of endogenous ligands, such as hormone replacement therapies, antioxidants, and enzyme inhibitors, to correct imbalances and protect against age-related decline.
Genetic and epigenetic interventions to influence the expression of genes involved in the synthesis, degradation, or response to endogenous ligands, potentially extending health-span and lifespan.
Understanding the role of endogenous ligands in protein inhibition and the aging process is crucial for developing targeted interventions to promote healthy aging and mitigate the effects of age-related diseases.
ROLE OF ENZYMES IN AGEING
Enzymes play critical roles in almost all biological processes, including those that contribute to aging and longevity. While enzymes typically catalyze reactions that facilitate proper cellular function, their dysregulation or aberrant activity can contribute to the aging process through various mechanisms. Here, we explore how certain enzymes are involved in protein inhibitions that lead to aging, highlighting their mechanisms and potential interventions.
Telomerase is an enzyme that adds repetitive nucleotide sequences to the ends of chromosomes, thereby extending telomeres and allowing cells to divide without losing vital genetic information. Most somatic cells have low telomerase activity, leading to telomere shortening with each cell division, contributing to cellular aging and senescence. Inhibition or loss of telomerase activity accelerates telomere shortening and the aging process.
DNA repair enzymes, such as those involved in the base excision repair (BER) pathway, nucleotide excision repair (NER) pathway, and mismatch repair (MMR) system, are crucial for correcting DNA damage. With age, the efficiency of these repair mechanisms declines, leading to an accumulation of DNA damage, genomic instability, and an increased rate of cell senescence and death.
The proteasome and autophagy-lysosome pathways are critical for degrading damaged or misfolded proteins. Age-related declines in the activity of enzymes involved in these pathways contribute to the accumulation of protein aggregates, a hallmark of cellular aging and a contributor to diseases such as Alzheimer’s and Parkinson’s.
Sirtuins are a family of NAD+-dependent deacetylases that regulate various cellular processes, including DNA repair, metabolic pathways, and inflammation. Sirtuins can promote longevity by enhancing cellular stress resistance and maintaining genomic stability. Decreased activity of sirtuins with age contributes to the aging process and the development of age-related diseases.
Advanced Glycation End-products (AGEs) are formed through non-enzymatic reactions between sugars and proteins, lipids, or nucleic acids, but certain enzymes can also catalyze the formation of AGEs. Accumulation of AGEs contributes to aging and age-related diseases by cross-linking proteins, impairing their function, and promoting inflammation and oxidative stress.
Strategies to safely activate telomerase in somatic cells are being explored to extend telomere length and enhance cellular lifespan.
Drugs or nutrients that boost the activity of DNA repair enzymes could mitigate genomic instability and its contributions to aging.
Compounds that enhance proteasome and autophagy activity could prevent the accumulation of toxic protein aggregates.
Molecules like resveratrol have been studied for their potential to activate sirtuins, promoting metabolic health and longevity.
Compounds that inhibit the formation of AGEs or break cross-links could alleviate the negative effects of AGE accumulation.
Understanding the roles of enzymes in protein inhibition and the aging process opens avenues for developing therapeutic strategies aimed at modulating enzyme activity to promote healthy aging and longevity.
ROLE OF NEUROCHEMICALS IN AGEING
Neurochemicals, including neurotransmitters, neuromodulators, and neurohormones, play crucial roles in the central nervous system (CNS), affecting cognition, mood, and neuronal health. Their interaction with proteins, either directly or through signaling pathways, can influence cellular processes that contribute to the aging process and the development of neurodegenerative diseases. Here, we explore the role of neurochemicals in protein inhibitions and their impact on aging.
Glutamate is the primary excitatory neurotransmitter in the CNS. While essential for synaptic plasticity and learning, excessive glutamate release and receptor activation can lead to excitotoxicity, a process where calcium influx and oxidative stress lead to neuronal injury and death. Excitotoxicity is implicated in the pathogenesis of various neurodegenerative diseases, such as Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS), contributing to age-related cognitive decline and neuronal loss.
Dopamine, a neurotransmitter associated with reward and motor control, can undergo auto-oxidation, forming reactive oxygen species (ROS) and quinones that can inhibit protein function through oxidative damage. In Parkinson’s disease (PD), the loss of dopaminergic neurons in the substantia nigra leads to decreased dopamine levels, contributing to motor symptoms. The metabolism of dopamine itself can contribute to the oxidative stress seen in PD, exacerbating neuronal damage.
Acetylcholine (ACh) is involved in learning, memory, and attention. In Alzheimer’s disease, there is a significant decline in cholinergic neurons and ACh levels, contributing to cognitive deficits. The inhibition of acetylcholinesterase, which breaks down ACh, is a therapeutic strategy used to increase ACh levels and mitigate cognitive symptoms in AD patients.
Amyloid beta (Aβ) and tau are proteins that accumulate abnormally in Alzheimer’s disease, contributing to neurodegeneration. Neurochemical imbalances can influence the pathogenesis of AD through mechanisms that promote Aβ aggregation and tau hyperphosphorylation, leading to the formation of plaques and tangles, respectively. For example, altered calcium signalling can contribute to the hyperphosphorylation of tau, while disruptions in neurotransmitter systems can influence Aβ production and aggregation.
Neuroinflammation is a hallmark of aging and neurodegenerative diseases. Cytokines and other inflammatory mediators can influence the expression and activity of proteins involved in neurodegenerative processes. For instance, pro-inflammatory cytokines can promote the expression of enzymes that catalyze the production of neurotoxic species, contributing to protein aggregation and neuronal damage.
Compounds that reduce oxidative stress or modulate dopamine metabolism may protect against dopaminergic neuron loss in PD.
Cholinesterase Inhibitors increase ACh availability, supporting cognitive function in AD patients.
Agents that regulate glutamate receptor activity can reduce excitotoxic damage, offering potential therapeutic benefits in diseases like AD and ALS. Strategies aimed at reducing Aβ aggregation or tau phosphorylation are being developed to directly address the pathological hallmarks of AD. Drugs that reduce neuroinflammation may mitigate cytokine-induced protein dysfunction and neurodegeneration. The intricate interplay between neurochemicals and protein function underscores the complexity of the aging brain and the development of neurodegenerative diseases. Understanding these relationships is crucial for developing targeted therapies to maintain cognitive health and mitigate the effects of aging on the CNS.
ROLE OF DRUG SUBSTANCES IN AGEING
Drug substances can have profound effects on the aging process, primarily through their interactions with proteins and modulation of their activities. These interactions can be beneficial, aiming to slow down or reverse aspects of aging, or detrimental, contributing to accelerated aging or the onset of age-related diseases. Here’s an overview of how drug substances can influence protein inhibition related to aging:
Rapamycin acts by inhibiting the mammalian target of rapamycin (mTOR) pathway, which is involved in protein synthesis and cell growth. By inhibiting this pathway, rapamycin can mimic the effects of caloric restriction, a known longevity enhancer, thus potentially slowing aging and extending lifespan.
Metformin is a diabetes medication that can increase insulin sensitivity and influence metabolic pathways associated with longevity. Metformin affects the AMP-activated protein kinase (AMPK) pathway, promoting improved cellular energy processes and potentially delaying aging.
Monoamine oxidase (MAO) inhibitors, used in the treatment of Parkinson’s disease and depression, can reduce the breakdown of neurotransmitters like dopamine, thus protecting against oxidative stress and neurodegeneration associated with aging.
Acetylcholinesterase Inhibitors used in Alzheimer’s disease, inhibit the enzyme that breaks down acetylcholine, thereby increasing its levels and improving cognitive function in patients with dementia. Vitamin E, Coenzyme Q10, and Polyphenols can act as antioxidants, protecting proteins and other cellular components from oxidative damage caused by free radicals, a key factor in the aging process.
Senolytics are class of drugs designed to selectively induce death of senescent cells. By clearing senescent cells, which contribute to aging and chronic diseases through their senescence-associated secretory phenotype (SASP), senolytics can potentially mitigate aging and promote tissue rejuvenation. Senescent cells are cells that have stopped dividing and have entered a state of permanent cell cycle arrest, but do not die as they normally would through the process of apoptosis. While senescence is a natural part of aging and serves important functions such as tumor suppression and wound healing, the accumulation of senescent cells is believed to contribute to various age-related diseases and conditions due to their secretion of pro-inflammatory cytokines, chemokines, and proteases, a phenomenon known as the senescence-associated secretory phenotype (SASP). Senolytics aim to target and eliminate these senescent cells to potentially alleviate or delay age-related diseases, improve health-span, and possibly extend lifespan. Senolytics work by exploiting the vulnerabilities in senescent cells’ survival pathways. One of the first senolytic combinations discovered, dasatinib is a cancer drug, and quercetin is a natural flavonoid found in many fruits and vegetables. Together, they have been shown to eliminate senescent cells in experimental models. Fisetin is another lnaturally occurring flavonoid with senolytic activity, found in strawberries and other fruits. Fisetin has shown potential in reducing the burden of senescent cells and improving health markers in aged animals. Senolytics represent an exciting frontier in biogerontology, offering a potential therapeutic avenue to combat aging and its associated diseases by directly targeting one of the underlying mechanisms of aging: the accumulation of senescent cells.
Sirtuins are a family of proteins that have been extensively studied for their roles in regulating cellular health, lifespan, and aging. These proteins, known for their enzymatic activity, primarily function as NAD+-dependent deacetylases or ADP-ribosyltransferases. Their activities link them directly to the metabolism of cells, influencing various cellular processes such as DNA repair, gene expression, apoptosis, inflammation, and stress resistance. The interest in sirtuins surged with the discovery of their potential to mimic the effects of caloric restriction, a known intervention that can extend lifespan in various organisms. Sirtuins are the subject of intense research for their potential therapeutic applications in aging and age-related diseases, including neurodegenerative diseases, cardiovascular diseases, and metabolic syndromes. By activating sirtuins, researchers hope to mimic the beneficial effects of caloric restriction without the need for dietary restriction.
NAD+ levels decline with age, affecting sirtuin activity and impairing DNA repair mechanisms. Supplementation with NAD+ precursors can enhance DNA repair, support mitochondrial function, and potentially delay aging processes.
While some drug substances show promise in extending lifespan and improving health-span, their long-term effects and potential adverse reactions must be carefully evaluated. For example, mTOR inhibitors like rapamycin can suppress the immune system, increasing susceptibility to infections. Metformin, while beneficial for metabolic health, may cause gastrointestinal disturbances and, in rare cases, lead to lactic acidosis.
Antioxidant supplements, in high doses, may interfere with cellular signalling and potentially lead to adverse health outcomes.
The development and use of drug substances targeting protein inhibition and modulation to influence aging are an area of intense research. These interventions hold promise for enhancing longevity and mitigating the effects of age-related diseases. However, their efficacy, safety, and long-term impacts require thorough investigation in clinical trials to ensure they are beneficial for human health.
THE ROLE OF CARBOHYDRATE CONSUMPTION IN THE AGING PROCESS
This is a subject of significant interest within nutritional science and gerontology. Carbohydrates, as a major macronutrient, provide the primary source of energy for the body but their impact on health and aging can vary greatly depending on the type, quality, and quantity of carbohydrates consumed. Here’s an overview of how carbohydrate consumption can influence the aging process:
Foods with a high GI cause rapid spikes in blood sugar levels, leading to increased insulin demand and potentially contributing to insulin resistance over time. Insulin resistance is a risk factor for type 2 diabetes, obesity, cardiovascular diseases, and possibly accelerated aging. In contrast, low GI foods result in slower blood sugar increases and are associated with lower risk of chronic diseases and might contribute to a healthier aging process.
Consuming high amounts of refined carbohydrates can promote the formation of AGEs, compounds that result from the reaction between sugars and proteins or lipids in the body. AGEs are implicated in the aging process and the development of age-related diseases by inducing oxidative stress and inflammation and by cross-linking with proteins, impairing their function.
Research has shown that caloric restriction, without malnutrition, can extend lifespan in various species. A diet low in calories but nutritionally dense, potentially lower in carbohydrates or consisting of mainly low GI carbohydrates, can mimic some effects of caloric restriction, promoting metabolic health and longevity
Diets rich in complex carbohydrates from whole grains, fruits, and vegetables, like the Mediterranean diet, are associated with reduced risks of chronic diseases and may support healthier aging. These diets are high in dietary fibre, antioxidants, and phytochemicals, which can mitigate inflammation and oxidative stress, contributing factors to aging.
The quality of carbohydrates consumed can significantly affect the gut microbiome, which plays a crucial role in immune function, nutrient absorption, and inflammation. Diets high in fibre from whole plant foods can promote a healthy gut microbiome, potentially influencing longevity positively.
The consumption of carbohydrates, particularly the type and quality, plays a significant role in the aging process. Diets high in refined sugars and high GI carbohydrates may accelerate aging through mechanisms like insulin resistance, formation of AGEs, and promotion of inflammatory pathways. Conversely, consuming a diet rich in low GI, complex carbohydrates from whole foods can support metabolic health, reduce inflammation, and potentially contribute to a longer, healthier lifespan.
In summary, focusing on the quality and quantity of carbohydrate intake, along with a balanced diet rich in whole foods, is essential for promoting healthy aging and minimizing the risk of age-related diseases.
Advanced Glycation End Products (AGEs) are a diverse group of compounds, their formation involves complex chemical reactions between proteins or lipids and reducing sugars, like glucose or fructose, through a non-enzymatic process called glycation.
Nε-(Carboxymethyl)lysine (CML) is one of the most studied and abundant AGEs in biological systems and food products. It forms through the glycation of the amino acid lysine. Nε-(Carboxyethyl)lysine (CEL) is similar to and is formed from lysine but involves an additional carbon in the alkylation chain. Methylglyoxal (MGO) s a highly reactive dicarbonyl compound that can modify proteins to form various AGEs, including hydroimidazolone types. Pentosidine is a well-known fluorescent cross-linking AGE, formed from the reaction between lysine and arginine residues in proteins with reducing sugars.
These examples illustrate the variety of molecular structures that AGEs can have. The diversity of AGEs, along with their complex formation and degradation mechanisms, makes them a challenging topic of study in biochemistry and medical research.
ROLE OF METABOLIC BY PRODUCTS IN AGEING PROCESS
Metabolic byproducts, often termed as metabolic waste products, play a significant role in the aging process. These byproducts result from the body’s metabolic activities and, depending on their levels and the efficiency of their clearance, can either be benign or contribute to aging and the development of age-related diseases. Key metabolic byproducts implicated in the aging process include reactive oxygen species (ROS), advanced glycation end products (AGEs), lipofuscin, and ammonia. Understanding their impact on cellular and organismal aging provides insights into potential interventions to promote healthy aging.
ROS are chemically reactive molecules containing oxygen. They are primarily produced in the mitochondria as a byproduct of the electron transport chain during ATP synthesis. While ROS play important roles in cell signalling and homeostasis, excessive ROS can cause oxidative stress, damaging DNA, proteins, and lipids. This damage contributes to cellular aging, senescence, and the pathogenesis of various age-related diseases, including cardiovascular diseases, neurodegeneration, and cancer.
Advanced Glycation End Products (AGEs)are formed through a non-enzymatic reaction between sugars and the amino groups of proteins, lipids, or nucleic acids. This process is accelerated in the presence of high glucose levels. AGEs accumulate with age and contribute to aging by cross-linking with proteins, thereby impairing their function and structural integrity. They also engage specific receptors, such as RAGE (receptor for AGEs), activating inflammatory pathways and promoting oxidative stress.
Lipofuscin is a complex mixture of oxidized proteins and lipids that accumulate as granules in the lysosomes of aging cells, particularly in post-mitotic cells like neurons and cardiac myocytes. The accumulation of lipofuscin within cells interferes with cellular homeostasis and lysosomal function, impairing the degradation and recycling of damaged organelles and proteins. This can contribute to cellular dysfunction and is associated with age-related declines in tissue function and diseases.
Ammonia is produced primarily through the breakdown of amino acids and nucleic acids. It is highly toxic at high concentrations and is usually rapidly converted into urea in the liver, which is then excreted in the urine.In cases of impaired liver function or disruptions in the urea cycle, ammonia levels can rise, leading to cellular toxicity and inflammation. Elevated ammonia levels have been implicated in neurological conditions and may contribute to cognitive decline associated with aging.
Supplementing with antioxidants can neutralize ROS, potentially reducing oxidative stress and its impacts on aging. Reducing dietary AGEs and adopting diets that lower blood sugar levels can decrease the formation of endogenous AGEs. Caloric restriction and intermittent fasting can improve mitochondrial function, reduce ROS production, and enhance the clearance of metabolic byproducts. Regular physical activity can enhance mitochondrial function and the efficiency of waste product clearance, promoting cellular health and longevity.
Understanding the role of metabolic byproducts in aging underscores the importance of lifestyle factors, such as diet and exercise, in managing their levels and mitigating their effects. Future research into interventions that can enhance the clearance of these byproducts or protect against their harmful effects may offer promising strategies for promoting healthy aging and extending lifespan.
ROLE OF ACIDITY OF CELLULAR MICROENVIRONMENT IN THE AGEING PROCESS
The acidity of the cellular microenvironment, often referred to in terms of pH levels, plays a crucial role in cellular function and has been implicated in the aging process and the development of age-related diseases. Cellular pH is tightly regulated, as even slight deviations can disrupt protein structure, enzyme activity, and overall cellular homeostasis. Enzymes, which catalyze all biochemical reactions in the body, have optimal pH ranges for their activity. Deviations from these optimal conditions can significantly reduce enzyme efficiency, affecting metabolic pathways and cellular processes essential for maintaining health and longevity. Age-related changes in cellular pH can disrupt enzyme function and protein structure, impairing metabolism and contributing to the accumulation of damaged macromolecules, a hallmark of aging.
Mitochondria, the cell’s powerhouses, have their own pH requirements for optimal function. The mitochondrial matrix needs to maintain a slightly alkaline environment for efficient ATP production. Age-related decline in mitochondrial function can be exacerbated by alterations in mitochondrial pH, leading to reduced energy production, increased oxidative stress, and accelerated cellular aging.
Autophagy, the process by which cells degrade and recycle their components, is pH-dependent. Lysosomes, which digest cellular waste, require an acidic environment to activate hydrolytic enzymes. Dysregulation of autophagy due to altered lysosomal pH contributes to the accumulation of damaged proteins and organelles, impairing cellular function and promoting aging.
The extracellular pH can influence immune cell function and inflammation. Acidic microenvironments are often found in sites of chronic inflammation and can modulate the activity of immune cells. Chronic low-grade inflammation or inflammaging is a key feature of aging. An acidic microenvironment can perpetuate inflammation and immune dysregulation, contributing to tissue damage and age-related diseases.
Intracellular pH influences calcium ion (Ca2+) levels and signalling. Ca2+ plays a critical role in various cellular processes, including muscle contraction, neurotransmission, and cell proliferation. Dysregulation of Ca2+ signalling, potentially influenced by changes in pH, has been associated with various age-related conditions, including cardiovascular diseases and neurodegeneration.
Understanding the role of cellular acidity in aging highlights potential therapeutic targets for mitigating age-related decline and diseases. Alkalizing diets or supplements that influence systemic and cellular pH levels is essential. Compounds that specifically target and modulate the pH of cellular compartments, such as proton pump inhibitors or buffers to restore optimal enzyme activity and cellular functions are useful. Drugs or nutrients that can restore or enhance autophagic processes, even under conditions of altered pH, and therapies that address chronic inflammation and may indirectly influence cellular pH through the reduction of metabolic waste products should be utilized. While the direct manipulation of cellular pH as an anti-aging strategy is complex and requires further research, maintaining a balanced cellular environment through lifestyle and dietary choices can contribute to healthier aging. Additionally, targeted research into how cellular pH influences aging processes may yield novel interventions for age-related diseases.
MOLECULAR IMPRINTED HOMEOPATHY DRUGS FOR RETARDING AGEING PROCESS
According to MIT explanations of scientific homeopathy, therapeutics involves of removal of the pathological molecular inhibitions using the molecular imprints of substances that are to those involved in producing those inhibitions. Molecular ‘locks’ and their ‘keys’ to be targetted are identified through minute study of molecular pathology. Substances that contain the ‘key’ molecules, or drug molecules having similar functional groups or moieties are procured, and their molecular imprints prepared through a process of homeopathic potentization, which is somewhat similar to the modern technology of molecular imprinting in polymers. Substances potentized above 12c, or diluted above avogadro limit, will contain only the molecular imprints of constituent molecules. When applied into the biological system, these molecular imprints can act as artificial binding pockets for the ‘’key molecules’, and remove the pathological molecular inhibitions they had produced. This is the underlying principle of Molecular Imprints Therapeutics or MIT. As per MIT perspective, molecular imprints prepared using chemical molecules that are activators, co-enzymes, substrates or inhibitors of concerned enzyme systems involved in the pathology of diseases could be used as safe and effective therapeutic agents.
Based on the understanding evolving from above discussions regarding molecular mechanism of ageing, senescence process could be retarded and longevity attained using homeopathic potentized forms of Lactic Acid 30, Ammonium Mur 30, Lipofuscin 30, Ferrum met 30, Metformin 30, Rapamycin 30, Cortisol 30, Hydrogen Peroxide 30, Tumor Necrosis Factor-a 30, insulin 30, Prostaglandin 30, Calc carb 30, Interleukin 30, Pentosidine 30 , Glutamic acid 30 etc. These drugs could be used as single medicines or as combinations.
INTERVENTIONS TO ATTAIN LONGEVITY
The biochemistry of aging and longevity encompasses a broad range of molecular, cellular, and physiological processes that contribute to the progression of aging and determine lifespan. Understanding these mechanisms is crucial for developing interventions to promote healthy aging and potentially extend lifespan. This article is an attempt to outline the key biochemical pathways and mechanisms involved in aging and longevity, and to discuss how the approach of MIT homeopathy and molecular imprinted drugs could be utilized in the management of geriatric health problems and to attain longevity.
Oxidative stress arises when there’s an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defenses of the cell. ROS are by-products of normal cellular metabolism, primarily generated in mitochondria. Over time, excessive ROS can damage DNA, proteins, and lipids, contributing to aging and age-related diseases. Antioxidant enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase play critical roles in neutralizing ROS, protecting cells from oxidative damage.
Telomeres are protective caps at the ends of chromosomes that shorten with each cell division. Once telomeres reach a critically short length, cells enter a state of replicative senescence or apoptosis, contributing to aging. The enzyme telomerase can elongate telomeres, promoting cellular longevity. However, telomerase activity is tightly regulated and is often repressed in somatic cells, making telomere maintenance a key focus in the study of aging and longevity.
Genomic instability, including DNA damage and mutation accumulation, is a hallmark of aging. Various endogenous and exogenous factors can induce DNA damage, while diminished DNA repair capabilities exacerbate the issue with age. The maintenance of genomic integrity, through mechanisms such as nucleotide excision repair, base excision repair, and DNA damage response pathways, is crucial for longevity.
Proteostasis involves the balance between protein synthesis, folding, trafficking, and degradation. Disruption in proteostasis, leading to the accumulation of misfolded or aggregated proteins, is associated with aging and many age-related diseases. Molecular chaperones and proteasomal and autophagic degradation pathways are vital for maintaining proteostasis.
Nutrient sensing pathways, including the insulin/IGF-1 signaling (IIS), mTOR, AMPK, and sirtuins, play significant roles in regulating metabolism, growth, and aging. Caloric restriction and interventions that modulate these pathways have been shown to extend lifespan in various model organisms. These pathways modulate an array of processes, from energy metabolism to stress resistance and autophagy, influencing the aging process.
Cellular senescence is a state of permanent cell cycle arrest induced by various stressors, including telomere shortening, DNA damage, and oncogene activation. Senescent cells accumulate with age and secrete pro-inflammatory factors (the senescence-associated secretory phenotype, or SASP), contributing to tissue dysfunction and age-related pathologies. Clearing senescent cells or modulating the SASP holds promise for mitigating aging effects.
Research in biochemistry of aging and longevity is rapidly advancing, with emerging areas such as epigenetic alterations, stem cell exhaustion, and intercellular communication gaining attention. Interventions like senolytics, NAD+ boosters, and rapamycin analogs are being explored for their potential to delay aging and extend healthy lifespan. Understanding the intricate web of biochemical pathways that contribute to aging and longevity is essential for developing effective strategies to enhance healthspan and potentially extend lifespan.
ROLE OF PROTEIN INHIBITIONS AND PROTEIN DEFORMATIONS
The role of protein inhibitions in the aging process encompasses a range of mechanisms that disrupt the balance of protein synthesis, folding, and degradation, collectively known as proteostasis. This disruption leads to the accumulation of misfolded or aggregated proteins, which is a hallmark of aging and is implicated in the onset and progression of age-related diseases. Here, we delve into several key areas where protein inhibition plays a significant role in the aging process:
Autophagy is a cellular process that degrades and recycles damaged organelles and proteins. With age, the efficiency of autophagy declines, leading to the accumulation of damaged proteins and organelles, contributing to cellular aging and dysfunction.
Proteasomal degradation involves the breakdown of proteins tagged with ubiquitin. Age-related decline in proteasome activity results in reduced protein degradation capacity, contributing to the buildup of damaged and misfolded proteins.S
Proteins with altered structures can form aggregates that are toxic to cells. Diseases such as Alzheimer’s (characterized by amyloid-beta and tau protein aggregates) and Parkinson’s (characterized by alpha-synuclein aggregates) exemplify how protein aggregation can lead to cellular dysfunction and disease. The age-related increase in protein aggregation contributes to the decline in cellular function and organismal aging.
Molecular chaperones assist in protein folding and prevent the aggregation of misfolded proteins. With aging, the expression levels and activity of chaperones decrease, impairing their protective role and allowing increased accumulation of misfolded proteins. This exacerbates cellular stress and contributes to the aging process.
Several signaling pathways that regulate protein synthesis and degradation are altered with aging, including the mTOR pathway and insulin/IGF-1 signaling pathway. Dysregulation of these pathways affects protein homeostasis, leading to increased susceptibility to stress and aging.
Chronic low-grade inflammation and oxidative stress are characteristic of aging and can directly inhibit the function of proteins through oxidative modifications. These modifications can alter protein structure and function, leading to a further decline in proteostasis and exacerbating the aging process.
Understanding the role of protein inhibitions in aging has led to the exploration of interventions aimed at restoring proteostasis, including:
Enhancement of autophagy and proteasomal activity through pharmacological agents or dietary interventions like caloric restriction.
Use of molecular chaperones as therapeutic agents to assist in the proper folding of proteins and prevent aggregation.
Modulation of signaling pathways (e.g., mTOR inhibitors like rapamycin) to restore balance in protein synthesis and degradation.
Antioxidants and anti-inflammatory compounds to mitigate oxidative stress and inflammation, thereby preserving protein function.
In summary, protein inhibition plays a crucial role in the aging process by disrupting proteostasis, leading to cellular dysfunction and the development of age-related diseases. Targeting the mechanisms underlying protein inhibition offers promising avenues for interventions aimed at promoting healthy aging and longevity.
ROLE OF ANTIBODIES IN AGEING PROCESS
Antibodies play a pivotal role in the immune system by recognizing and binding to specific antigens, such as pathogens or foreign substances, facilitating their neutralization or destruction. However, in the context of protein inhibitions, antibodies can also recognize and bind to specific proteins within the body, affecting their function in several ways. This interaction between antibodies and proteins is crucial in both therapeutic interventions and the pathogenesis of certain diseases.
Therapeutic antibodies can be designed to target and neutralize pathogenic proteins, such as toxins or proteins that viruses use to enter host cells. For example, antibodies against the spike protein of SARS-CoV-2 can prevent the virus from infecting cells.
In conditions characterized by the accumulation of misfolded proteins, such as Alzheimer’s disease, antibodies can be engineered to recognize and promote the clearance of these proteins. This approach aims to reduce the toxic effects of protein aggregates on cell function.
Certain therapeutic antibodies can inhibit the action of immune system proteins that promote inflammation and autoimmune responses. For instance, antibodies targeting tumor necrosis factor-alpha (TNF-α) are used in treating autoimmune diseases like rheumatoid arthritis, by reducing inflammation and tissue damage.
In autoimmune conditions, the body produces autoantibodies that mistakenly target and inhibit the function of its own proteins. This can lead to a wide range of dysfunctions depending on the proteins targeted. For example, in myasthenia gravis, autoantibodies bind to acetylcholine receptors at the neuromuscular junction, impairing muscle contraction.
Autoantibodies can directly inhibit the function of essential proteins by binding to active sites or regions critical for their activity. This can disrupt normal physiological processes and lead to disease symptoms.
Antibodies bound to circulating proteins can form immune complexes that deposit in tissues, leading to inflammation and tissue damage, as seen in conditions like systemic lupus erythematosus (SLE).
Antibodies can influence protein function significantly, serving both as essential tools for therapeutic intervention and diagnostics and as key players in the pathogenesis of various diseases. Understanding the interactions between antibodies and proteins is critical for developing new therapies and for the diagnosis and treatment of diseases.
ROLE OF PHYTOCHEMICALS IN AGEING
Phytochemicals are bioactive compounds found in plants that have various effects on human health, including antioxidant, anti-inflammatory, and anticarcinogenic properties. In the context of protein inhibition, phytochemicals can modulate protein function in several key ways, offering potential therapeutic benefits for a range of diseases, including cancer, neurodegenerative disorders, and cardiovascular diseases. Here, we explore the role of phytochemicals in protein inhibition, highlighting their mechanisms of action and implications for health and disease.
Many phytochemicals possess strong antioxidant properties, enabling them to neutralize reactive oxygen species (ROS) and reduce oxidative stress. Oxidative stress can lead to the oxidative modification of proteins, impairing their function and contributing to the pathogenesis of various diseases. By inhibiting oxidative stress, phytochemicals help maintain protein integrity and function.
Flavonoids, found in fruits, vegetables, tea, and wine, can directly scavenge ROS and upregulate antioxidant defense enzymes, thereby protecting proteins from oxidative damage.
Certain phytochemicals can directly inhibit the activity of specific enzymes involved in disease processes. This inhibition can modulate signaling pathways, metabolism, and the progression of diseases. Curcumin, a compound found in turmeric, can inhibit the activity of cyclooxygenase-2 (COX-2), an enzyme involved in inflammation, potentially offering benefits in conditions like arthritis and cancer.
Phytochemicals can also interfere with the aggregation of misfolded proteins, a feature common in neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease. By inhibiting protein aggregation, these compounds can potentially slow the progression of these conditions.
Epigallocatechin gallate (EGCG), a polyphenol in green tea, has been shown to inhibit the aggregation of beta-amyloid peptides in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease.
Phytochemicals can influence the expression levels of various proteins, including those involved in cell cycle regulation, apoptosis, and detoxification, through their actions on transcription factors and signaling pathways. Sulforaphane, found in cruciferous vegetables like broccoli, can activate the Nrf2 pathway, leading to the increased expression of detoxifying and antioxidant enzymes.
Some phytochemicals can bind to cellular receptors or signaling molecules, altering signal transduction pathways and affecting cell growth, apoptosis, and differentiation. Genistein, an isoflavone from soy, can bind to estrogen receptors, modulating the effects of estrogen on target tissues and potentially offering benefits in hormone-related cancers.
The role of phytochemicals in protein inhibition has significant implications for the prevention and treatment of diseases. Their natural origin and wide range of bioactivities make them attractive candidates for developing new therapeutic agents. However, more research is needed to fully understand their mechanisms of action, optimal doses, bioavailability, and potential side effects. Clinical trials are essential to confirm the health benefits of phytochemicals and to develop guidelines for their use in disease prevention and therapy.
ROLE OF ELEMENTAL CHEMICALS IN AGEING
Elemental chemicals, particularly metals, can play a significant role in protein inhibition, contributing to the aging process and the development of age-related diseases. While some metals are essential for life, acting as cofactors for various enzymes and playing roles in numerous biochemical pathways, others can be toxic, especially at high concentrations. Their interaction with proteins can lead to alterations in protein structure and function, oxidative stress, and disruption of cellular homeostasis, all of which are implicated in aging and its associated diseases.
Iron is essential for many biological processes, including oxygen transport and DNA synthesis. However, excessive iron can catalyze the formation of highly reactive hydroxyl radicals through the Fenton reaction, leading to oxidative damage to proteins, lipids, and DNA. This oxidative stress is a significant contributor to the aging process and the development of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, where iron accumulation in the brain has been observed.
Copper is another essential metal that serves as a cofactor for enzymes involved in energy production, antioxidant defenses, and neurotransmitter synthesis. However, like iron, excessive copper can contribute to oxidative stress by generating reactive oxygen species (ROS). Copper imbalance has been linked to neurodegenerative diseases and is known to catalyze the formation of toxic aggregates of proteins, such as beta-amyloid in Alzheimer’s disease.
Zinc is crucial for immune function, antioxidant defense, and DNA repair. It can also inhibit the aggregation of amyloid-beta peptides in vitro, suggesting a protective role in Alzheimer’s disease. However, dysregulation in zinc homeostasis can disrupt cellular functions and contribute to the aging process. For example, high concentrations of zinc can interfere with the function of various signaling proteins and enzymes.
Lead and mercury are toxic metals with no known essential biological function. Exposure to these metals can inhibit the activity of enzymes and disrupt protein function through the displacement of essential metals from their binding sites or direct interaction with thiol groups in proteins. This can lead to cellular toxicity, oxidative stress, and inflammation, contributing to the aging process and increasing the risk of age-related diseases.
Aluminum exposure has been suggested to play a role in the aging process and neurodegeneration, although the evidence is controversial. Aluminum can compete with essential metals for binding sites on proteins and enzymes, potentially altering their structure and function. It may also induce oxidative stress and inflammation, contributing to cellular aging.
Given the role of elemental chemicals in protein inhibition and the aging process, strategies to mitigate their effects include: Maintaining a balanced intake of essential metals through diet and possibly using specific chelators to reduce the bioavailability of toxic metals. Using antioxidants to counteract the oxidative stress induced by metal imbalance. Minimizing exposure to toxic metals through environmental regulations and personal protective measures.
Understanding the complex interplay between elemental chemicals and protein function is critical for developing strategies to mitigate their contributions to the aging process and to promote healthy aging.
ROLE OF ENDOGENOUS LIGANDS IN AGEING
Endogenous ligands, which include hormones, neurotransmitters, and other naturally occurring molecules within the body, can modulate protein activity through various mechanisms. Their role in protein inhibition can significantly impact cellular function and contribute to the aging process, affecting longevity, cellular senescence, and the development of age-related diseases. Here, we explore how endogenous ligands influence protein inhibition and its implications for aging.
Insulin and IGF-1 (Insulin-like Growth Factor-1): Elevated levels of insulin and IGF-1 can accelerate aging through the promotion of anabolic processes, including cell growth and proliferation. These hormones activate the insulin/IGF-1 signaling pathway, which has been implicated in the aging process. Inhibition of this pathway, through reduced levels of these ligands, has been shown to extend lifespan in various organisms by enhancing stress resistance and promoting metabolic efficiency.
This stress hormone cortisol can inhibit protein synthesis and increase protein degradation, contributing to muscle wasting and other age-related declines in tissue function. Chronic elevation of cortisol, often resulting from prolonged stress, can accelerate aging processes by promoting oxidative stress, inflammation, and cellular senescence.
The neurotransmitter Acetylcholine plays a crucial role in muscle function and cognitive processes. Its decline is associated with aging, particularly in conditions like Alzheimer’s disease, where acetylcholine-producing neurons deteriorate. Enhancing acetylcholine levels or activity, through inhibition of the enzyme acetylcholinesterase which breaks down acetylcholine, is a strategy used in the treatment of Alzheimer’s disease to improve cognitive function.
Dopamine levels decrease with age, impacting movement control and potentially contributing to the development of Parkinson’s disease. The inhibition of dopamine reuptake or degradation to increase its availability is a common therapeutic approach in managing Parkinson’s disease symptoms.
Although not ligands in the classical sense, Reactive Oxygen Species or ROS can act as signalling molecules that modulate protein function. Excessive ROS can inhibit the function of key cellular proteins through oxidative modifications, contributing to cellular aging and dysfunction. The body’s antioxidant defence mechanisms, which include endogenously produced molecules like glutathione, are crucial for counteracting ROS-mediated protein inhibition.
Nitric Oxide (NO) is a signaling molecule that influences various physiological processes, including vasodilation and neurotransmission. Dysregulation of NO production can contribute to vascular aging and neurodegeneration. In certain contexts, NO can inhibit mitochondrial function and enzyme activity, impacting cellular energy production and contributing to aging processes.
Targeting the interaction between endogenous ligands and proteins offers potential strategies for modulating the aging process. These include:
Lifestyle interventions, such as diet and exercise, to modulate hormone levels naturally.
Pharmacological agents that mimic, enhance, or inhibit the action of endogenous ligands, such as hormone replacement therapies, antioxidants, and enzyme inhibitors, to correct imbalances and protect against age-related decline.
Genetic and epigenetic interventions to influence the expression of genes involved in the synthesis, degradation, or response to endogenous ligands, potentially extending health-span and lifespan.
Understanding the role of endogenous ligands in protein inhibition and the aging process is crucial for developing targeted interventions to promote healthy aging and mitigate the effects of age-related diseases.
ROLE OF ENZYMES IN AGEING
Enzymes play critical roles in almost all biological processes, including those that contribute to aging and longevity. While enzymes typically catalyze reactions that facilitate proper cellular function, their dysregulation or aberrant activity can contribute to the aging process through various mechanisms. Here, we explore how certain enzymes are involved in protein inhibitions that lead to aging, highlighting their mechanisms and potential interventions.
Telomerase is an enzyme that adds repetitive nucleotide sequences to the ends of chromosomes, thereby extending telomeres and allowing cells to divide without losing vital genetic information. Most somatic cells have low telomerase activity, leading to telomere shortening with each cell division, contributing to cellular aging and senescence. Inhibition or loss of telomerase activity accelerates telomere shortening and the aging process.
DNA repair enzymes, such as those involved in the base excision repair (BER) pathway, nucleotide excision repair (NER) pathway, and mismatch repair (MMR) system, are crucial for correcting DNA damage. With age, the efficiency of these repair mechanisms declines, leading to an accumulation of DNA damage, genomic instability, and an increased rate of cell senescence and death.
The proteasome and autophagy-lysosome pathways are critical for degrading damaged or misfolded proteins. Age-related declines in the activity of enzymes involved in these pathways contribute to the accumulation of protein aggregates, a hallmark of cellular aging and a contributor to diseases such as Alzheimer’s and Parkinson’s.
Sirtuins are a family of NAD+-dependent deacetylases that regulate various cellular processes, including DNA repair, metabolic pathways, and inflammation. Sirtuins can promote longevity by enhancing cellular stress resistance and maintaining genomic stability. Decreased activity of sirtuins with age contributes to the aging process and the development of age-related diseases.
Advanced Glycation End-products (AGEs) are formed through non-enzymatic reactions between sugars and proteins, lipids, or nucleic acids, but certain enzymes can also catalyze the formation of AGEs. Accumulation of AGEs contributes to aging and age-related diseases by cross-linking proteins, impairing their function, and promoting inflammation and oxidative stress.
Strategies to safely activate telomerase in somatic cells are being explored to extend telomere length and enhance cellular lifespan.
Drugs or nutrients that boost the activity of DNA repair enzymes could mitigate genomic instability and its contributions to aging.
Compounds that enhance proteasome and autophagy activity could prevent the accumulation of toxic protein aggregates.
Molecules like resveratrol have been studied for their potential to activate sirtuins, promoting metabolic health and longevity.
Compounds that inhibit the formation of AGEs or break cross-links could alleviate the negative effects of AGE accumulation.
Understanding the roles of enzymes in protein inhibition and the aging process opens avenues for developing therapeutic strategies aimed at modulating enzyme activity to promote healthy aging and longevity.
ROLE OF NEUROCHEMICALS IN AGEING
Neurochemicals, including neurotransmitters, neuromodulators, and neurohormones, play crucial roles in the central nervous system (CNS), affecting cognition, mood, and neuronal health. Their interaction with proteins, either directly or through signaling pathways, can influence cellular processes that contribute to the aging process and the development of neurodegenerative diseases. Here, we explore the role of neurochemicals in protein inhibitions and their impact on aging.
Glutamate is the primary excitatory neurotransmitter in the CNS. While essential for synaptic plasticity and learning, excessive glutamate release and receptor activation can lead to excitotoxicity, a process where calcium influx and oxidative stress lead to neuronal injury and death. Excitotoxicity is implicated in the pathogenesis of various neurodegenerative diseases, such as Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS), contributing to age-related cognitive decline and neuronal loss.
Dopamine, a neurotransmitter associated with reward and motor control, can undergo auto-oxidation, forming reactive oxygen species (ROS) and quinones that can inhibit protein function through oxidative damage. In Parkinson’s disease (PD), the loss of dopaminergic neurons in the substantia nigra leads to decreased dopamine levels, contributing to motor symptoms. The metabolism of dopamine itself can contribute to the oxidative stress seen in PD, exacerbating neuronal damage.
Acetylcholine (ACh) is involved in learning, memory, and attention. In Alzheimer’s disease, there is a significant decline in cholinergic neurons and ACh levels, contributing to cognitive deficits. The inhibition of acetylcholinesterase, which breaks down ACh, is a therapeutic strategy used to increase ACh levels and mitigate cognitive symptoms in AD patients.
Amyloid beta (Aβ) and tau are proteins that accumulate abnormally in Alzheimer’s disease, contributing to neurodegeneration. Neurochemical imbalances can influence the pathogenesis of AD through mechanisms that promote Aβ aggregation and tau hyperphosphorylation, leading to the formation of plaques and tangles, respectively. For example, altered calcium signalling can contribute to the hyperphosphorylation of tau, while disruptions in neurotransmitter systems can influence Aβ production and aggregation.
Neuroinflammation is a hallmark of aging and neurodegenerative diseases. Cytokines and other inflammatory mediators can influence the expression and activity of proteins involved in neurodegenerative processes. For instance, pro-inflammatory cytokines can promote the expression of enzymes that catalyze the production of neurotoxic species, contributing to protein aggregation and neuronal damage.
Compounds that reduce oxidative stress or modulate dopamine metabolism may protect against dopaminergic neuron loss in PD.
Cholinesterase Inhibitors increase ACh availability, supporting cognitive function in AD patients.
Agents that regulate glutamate receptor activity can reduce excitotoxic damage, offering potential therapeutic benefits in diseases like AD and ALS. Strategies aimed at reducing Aβ aggregation or tau phosphorylation are being developed to directly address the pathological hallmarks of AD. Drugs that reduce neuroinflammation may mitigate cytokine-induced protein dysfunction and neurodegeneration. The intricate interplay between neurochemicals and protein function underscores the complexity of the aging brain and the development of neurodegenerative diseases. Understanding these relationships is crucial for developing targeted therapies to maintain cognitive health and mitigate the effects of aging on the CNS.
ROLE OF DRUG SUBSTANCES IN AGEING
Drug substances can have profound effects on the aging process, primarily through their interactions with proteins and modulation of their activities. These interactions can be beneficial, aiming to slow down or reverse aspects of aging, or detrimental, contributing to accelerated aging or the onset of age-related diseases. Here’s an overview of how drug substances can influence protein inhibition related to aging:
Rapamycin acts by inhibiting the mammalian target of rapamycin (mTOR) pathway, which is involved in protein synthesis and cell growth. By inhibiting this pathway, rapamycin can mimic the effects of caloric restriction, a known longevity enhancer, thus potentially slowing aging and extending lifespan.
Metformin is a diabetes medication that can increase insulin sensitivity and influence metabolic pathways associated with longevity. Metformin affects the AMP-activated protein kinase (AMPK) pathway, promoting improved cellular energy processes and potentially delaying aging.
Monoamine oxidase (MAO) inhibitors, used in the treatment of Parkinson’s disease and depression, can reduce the breakdown of neurotransmitters like dopamine, thus protecting against oxidative stress and neurodegeneration associated with aging.
Acetylcholinesterase Inhibitors used in Alzheimer’s disease, inhibit the enzyme that breaks down acetylcholine, thereby increasing its levels and improving cognitive function in patients with dementia. Vitamin E, Coenzyme Q10, and Polyphenols can act as antioxidants, protecting proteins and other cellular components from oxidative damage caused by free radicals, a key factor in the aging process.
Senolytics are class of drugs designed to selectively induce death of senescent cells. By clearing senescent cells, which contribute to aging and chronic diseases through their senescence-associated secretory phenotype (SASP), senolytics can potentially mitigate aging and promote tissue rejuvenation. Senescent cells are cells that have stopped dividing and have entered a state of permanent cell cycle arrest, but do not die as they normally would through the process of apoptosis. While senescence is a natural part of aging and serves important functions such as tumor suppression and wound healing, the accumulation of senescent cells is believed to contribute to various age-related diseases and conditions due to their secretion of pro-inflammatory cytokines, chemokines, and proteases, a phenomenon known as the senescence-associated secretory phenotype (SASP). Senolytics aim to target and eliminate these senescent cells to potentially alleviate or delay age-related diseases, improve health-span, and possibly extend lifespan. Senolytics work by exploiting the vulnerabilities in senescent cells’ survival pathways. One of the first senolytic combinations discovered, dasatinib is a cancer drug, and quercetin is a natural flavonoid found in many fruits and vegetables. Together, they have been shown to eliminate senescent cells in experimental models. Fisetin is another lnaturally occurring flavonoid with senolytic activity, found in strawberries and other fruits. Fisetin has shown potential in reducing the burden of senescent cells and improving health markers in aged animals. Senolytics represent an exciting frontier in biogerontology, offering a potential therapeutic avenue to combat aging and its associated diseases by directly targeting one of the underlying mechanisms of aging: the accumulation of senescent cells.
Sirtuins are a family of proteins that have been extensively studied for their roles in regulating cellular health, lifespan, and aging. These proteins, known for their enzymatic activity, primarily function as NAD+-dependent deacetylases or ADP-ribosyltransferases. Their activities link them directly to the metabolism of cells, influencing various cellular processes such as DNA repair, gene expression, apoptosis, inflammation, and stress resistance. The interest in sirtuins surged with the discovery of their potential to mimic the effects of caloric restriction, a known intervention that can extend lifespan in various organisms. Sirtuins are the subject of intense research for their potential therapeutic applications in aging and age-related diseases, including neurodegenerative diseases, cardiovascular diseases, and metabolic syndromes. By activating sirtuins, researchers hope to mimic the beneficial effects of caloric restriction without the need for dietary restriction.
NAD+ levels decline with age, affecting sirtuin activity and impairing DNA repair mechanisms. Supplementation with NAD+ precursors can enhance DNA repair, support mitochondrial function, and potentially delay aging processes.
While some drug substances show promise in extending lifespan and improving health-span, their long-term effects and potential adverse reactions must be carefully evaluated. For example, mTOR inhibitors like rapamycin can suppress the immune system, increasing susceptibility to infections. Metformin, while beneficial for metabolic health, may cause gastrointestinal disturbances and, in rare cases, lead to lactic acidosis.
Antioxidant supplements, in high doses, may interfere with cellular signalling and potentially lead to adverse health outcomes.
The development and use of drug substances targeting protein inhibition and modulation to influence aging are an area of intense research. These interventions hold promise for enhancing longevity and mitigating the effects of age-related diseases. However, their efficacy, safety, and long-term impacts require thorough investigation in clinical trials to ensure they are beneficial for human health.
THE ROLE OF CARBOHYDRATE CONSUMPTION IN THE AGING PROCESS
This is a subject of significant interest within nutritional science and gerontology. Carbohydrates, as a major macronutrient, provide the primary source of energy for the body but their impact on health and aging can vary greatly depending on the type, quality, and quantity of carbohydrates consumed. Here’s an overview of how carbohydrate consumption can influence the aging process:
Foods with a high GI cause rapid spikes in blood sugar levels, leading to increased insulin demand and potentially contributing to insulin resistance over time. Insulin resistance is a risk factor for type 2 diabetes, obesity, cardiovascular diseases, and possibly accelerated aging. In contrast, low GI foods result in slower blood sugar increases and are associated with lower risk of chronic diseases and might contribute to a healthier aging process.
Consuming high amounts of refined carbohydrates can promote the formation of AGEs, compounds that result from the reaction between sugars and proteins or lipids in the body. AGEs are implicated in the aging process and the development of age-related diseases by inducing oxidative stress and inflammation and by cross-linking with proteins, impairing their function.
Research has shown that caloric restriction, without malnutrition, can extend lifespan in various species. A diet low in calories but nutritionally dense, potentially lower in carbohydrates or consisting of mainly low GI carbohydrates, can mimic some effects of caloric restriction, promoting metabolic health and longevity
Diets rich in complex carbohydrates from whole grains, fruits, and vegetables, like the Mediterranean diet, are associated with reduced risks of chronic diseases and may support healthier aging. These diets are high in dietary fibre, antioxidants, and phytochemicals, which can mitigate inflammation and oxidative stress, contributing factors to aging.
The quality of carbohydrates consumed can significantly affect the gut microbiome, which plays a crucial role in immune function, nutrient absorption, and inflammation. Diets high in fibre from whole plant foods can promote a healthy gut microbiome, potentially influencing longevity positively.
The consumption of carbohydrates, particularly the type and quality, plays a significant role in the aging process. Diets high in refined sugars and high GI carbohydrates may accelerate aging through mechanisms like insulin resistance, formation of AGEs, and promotion of inflammatory pathways. Conversely, consuming a diet rich in low GI, complex carbohydrates from whole foods can support metabolic health, reduce inflammation, and potentially contribute to a longer, healthier lifespan.
In summary, focusing on the quality and quantity of carbohydrate intake, along with a balanced diet rich in whole foods, is essential for promoting healthy aging and minimizing the risk of age-related diseases.
Advanced Glycation End Products (AGEs) are a diverse group of compounds, their formation involves complex chemical reactions between proteins or lipids and reducing sugars, like glucose or fructose, through a non-enzymatic process called glycation.
Nε-(Carboxymethyl)lysine (CML) is one of the most studied and abundant AGEs in biological systems and food products. It forms through the glycation of the amino acid lysine. Nε-(Carboxyethyl)lysine (CEL) is similar to and is formed from lysine but involves an additional carbon in the alkylation chain. Methylglyoxal (MGO) s a highly reactive dicarbonyl compound that can modify proteins to form various AGEs, including hydroimidazolone types. Pentosidine is a well-known fluorescent cross-linking AGE, formed from the reaction between lysine and arginine residues in proteins with reducing sugars.
These examples illustrate the variety of molecular structures that AGEs can have. The diversity of AGEs, along with their complex formation and degradation mechanisms, makes them a challenging topic of study in biochemistry and medical research.
ROLE OF METABOLIC BY PRODUCTS IN AGEING PROCESS
Metabolic byproducts, often termed as metabolic waste products, play a significant role in the aging process. These byproducts result from the body’s metabolic activities and, depending on their levels and the efficiency of their clearance, can either be benign or contribute to aging and the development of age-related diseases. Key metabolic byproducts implicated in the aging process include reactive oxygen species (ROS), advanced glycation end products (AGEs), lipofuscin, and ammonia. Understanding their impact on cellular and organismal aging provides insights into potential interventions to promote healthy aging.
ROS are chemically reactive molecules containing oxygen. They are primarily produced in the mitochondria as a byproduct of the electron transport chain during ATP synthesis. While ROS play important roles in cell signalling and homeostasis, excessive ROS can cause oxidative stress, damaging DNA, proteins, and lipids. This damage contributes to cellular aging, senescence, and the pathogenesis of various age-related diseases, including cardiovascular diseases, neurodegeneration, and cancer.
Advanced Glycation End Products (AGEs)are formed through a non-enzymatic reaction between sugars and the amino groups of proteins, lipids, or nucleic acids. This process is accelerated in the presence of high glucose levels. AGEs accumulate with age and contribute to aging by cross-linking with proteins, thereby impairing their function and structural integrity. They also engage specific receptors, such as RAGE (receptor for AGEs), activating inflammatory pathways and promoting oxidative stress.
Lipofuscin is a complex mixture of oxidized proteins and lipids that accumulate as granules in the lysosomes of aging cells, particularly in post-mitotic cells like neurons and cardiac myocytes. The accumulation of lipofuscin within cells interferes with cellular homeostasis and lysosomal function, impairing the degradation and recycling of damaged organelles and proteins. This can contribute to cellular dysfunction and is associated with age-related declines in tissue function and diseases.
Ammonia is produced primarily through the breakdown of amino acids and nucleic acids. It is highly toxic at high concentrations and is usually rapidly converted into urea in the liver, which is then excreted in the urine.In cases of impaired liver function or disruptions in the urea cycle, ammonia levels can rise, leading to cellular toxicity and inflammation. Elevated ammonia levels have been implicated in neurological conditions and may contribute to cognitive decline associated with aging.
Supplementing with antioxidants can neutralize ROS, potentially reducing oxidative stress and its impacts on aging. Reducing dietary AGEs and adopting diets that lower blood sugar levels can decrease the formation of endogenous AGEs. Caloric restriction and intermittent fasting can improve mitochondrial function, reduce ROS production, and enhance the clearance of metabolic byproducts. Regular physical activity can enhance mitochondrial function and the efficiency of waste product clearance, promoting cellular health and longevity.
Understanding the role of metabolic byproducts in aging underscores the importance of lifestyle factors, such as diet and exercise, in managing their levels and mitigating their effects. Future research into interventions that can enhance the clearance of these byproducts or protect against their harmful effects may offer promising strategies for promoting healthy aging and extending lifespan.
ROLE OF ACIDITY OF CELLULAR MICROENVIRONMENT IN THE AGEING PROCESS
The acidity of the cellular microenvironment, often referred to in terms of pH levels, plays a crucial role in cellular function and has been implicated in the aging process and the development of age-related diseases. Cellular pH is tightly regulated, as even slight deviations can disrupt protein structure, enzyme activity, and overall cellular homeostasis. Enzymes, which catalyze all biochemical reactions in the body, have optimal pH ranges for their activity. Deviations from these optimal conditions can significantly reduce enzyme efficiency, affecting metabolic pathways and cellular processes essential for maintaining health and longevity. Age-related changes in cellular pH can disrupt enzyme function and protein structure, impairing metabolism and contributing to the accumulation of damaged macromolecules, a hallmark of aging.
Mitochondria, the cell’s powerhouses, have their own pH requirements for optimal function. The mitochondrial matrix needs to maintain a slightly alkaline environment for efficient ATP production. Age-related decline in mitochondrial function can be exacerbated by alterations in mitochondrial pH, leading to reduced energy production, increased oxidative stress, and accelerated cellular aging.
Autophagy, the process by which cells degrade and recycle their components, is pH-dependent. Lysosomes, which digest cellular waste, require an acidic environment to activate hydrolytic enzymes. Dysregulation of autophagy due to altered lysosomal pH contributes to the accumulation of damaged proteins and organelles, impairing cellular function and promoting aging.
The extracellular pH can influence immune cell function and inflammation. Acidic microenvironments are often found in sites of chronic inflammation and can modulate the activity of immune cells. Chronic low-grade inflammation or inflammaging is a key feature of aging. An acidic microenvironment can perpetuate inflammation and immune dysregulation, contributing to tissue damage and age-related diseases.
Intracellular pH influences calcium ion (Ca2+) levels and signalling. Ca2+ plays a critical role in various cellular processes, including muscle contraction, neurotransmission, and cell proliferation. Dysregulation of Ca2+ signalling, potentially influenced by changes in pH, has been associated with various age-related conditions, including cardiovascular diseases and neurodegeneration.
Understanding the role of cellular acidity in aging highlights potential therapeutic targets for mitigating age-related decline and diseases. Alkalizing diets or supplements that influence systemic and cellular pH levels is essential. Compounds that specifically target and modulate the pH of cellular compartments, such as proton pump inhibitors or buffers to restore optimal enzyme activity and cellular functions are useful. Drugs or nutrients that can restore or enhance autophagic processes, even under conditions of altered pH, and therapies that address chronic inflammation and may indirectly influence cellular pH through the reduction of metabolic waste products should be utilized. While the direct manipulation of cellular pH as an anti-aging strategy is complex and requires further research, maintaining a balanced cellular environment through lifestyle and dietary choices can contribute to healthier aging. Additionally, targeted research into how cellular pH influences aging processes may yield novel interventions for age-related diseases.
MOLECULAR IMPRINTED HOMEOPATHY DRUGS FOR RETARDING AGEING PROCESS
MIT or Molecular Imprints Therapeutics refers to a scientific hypothesis that proposes a rational model for biological mechanism of homeopathic therapeutics.
According to MIT hypothesis, potentization involves a process of ‘molecular imprinting’, where in the conformational details of individual drug molecules are ‘imprinted or engraved as hydrogen- bonded three dimensional nano-cavities into a supra-molecular matrix of water and ethyl alcohol, through a process of molecular level ‘host-guest’ interactions. These ‘molecular imprints’ are the active principles of post-avogadro dilutions used as homeopathic drugs. Due to ‘conformational affinity’, molecular imprints can act as ‘artificial key holes or ligand binds’ for the specific drug molecules used for imprinting, and for all pathogenic molecules having functional groups ‘similar’ to those drug molecules. When used as therapeutic agents, molecular imprints selectively bind to the pathogenic molecules having conformational affinity and deactivate them, thereby relieving the biological molecules from the inhibitions or blocks caused by pathogenic molecules.
According to MIT hypothesis, this is the biological mechanism of high dilution therapeutics involved in homeopathic cure. According to MIT hypothesis, ‘Similia Similibus Curentur’ means, diseases expressed through a particular group of symptoms could be cured by ‘molecular imprints’ forms of drug substances, which in ‘molecular’ or crude forms could produce ‘similar’ groups of symptoms in healthy individuals. ‘Similarity’ of drug symptoms and diseaes indicates ‘similarity’ of pathological molecular inhibitions caused by drug molecules and pathogenic molecules, which in turn indicates conformational ‘similarity’ of functional groups of drug molecules and pathogenic molecules. Since molecular imprints of ‘similar’ molecules can bind to ‘similar ligand molecules by conformational affinity, they can act as the therapeutics agents when applied as indicated by ‘similarity of symptoms. Nobody in the whole history could so far propose a hypothesis about homeopathy as scientific, rational and perfect as MIT explaining the molecular process involed in potentization, and the biological mechanism involved in ‘similiasimilibus- curentur, in a way fitting well to modern scientific knowledge system.
If symptoms expressed in a particular disease condition as well as symptoms produced in a healthy individual by a particular drug substance were similar, it means the disease-causing molecules and the drug molecules could bind to same biological targets and produce similar molecular errors, which in turn means both of them have similar functional groups or molecular conformations. This phenomenon of competitive relationship between similar chemical molecules in binding to similar biological targets scientifically explains the fundamental homeopathic principle Similia Similibus Curentur.
Practically, MIT or Molecular Imprints Therapeutics is all about identifying the specific target-ligand ‘key-lock’ mechanism involved in the molecular pathology of the particular disease, procuring the samples of concerned ligand molecules or molecules that can mimic as the ligands by conformational similarity, preparing their molecular imprints through a process of homeopathic potentization upto 30c potency, and using that preparation as therapeutic agent.
Since individual molecular imprints contained in drugs potentized above avogadro limit cannot interact each other or interfere in the normal interactions between biological molecules and their natural ligands, and since they can act only as artificial binding sites for specific pathogentic molecules having conformational affinity, there cannot by any adverse effects or reduction in medicinal effects even if we mix two or more potentized drugs together, or prescribe them simultaneously- they will work.
Based on the understanding evolving from above discussions regarding molecular mechanism of ageing, senescence process could be retarded and longevity attained using homeopathic potentized forms of Lactic Acid 30, Ammonium Mur 30, Lipofuscin 30, Ferrum met 30, Metformin 30, Rapamycin 30, Cortisol 30, Hydrogen Peroxide 30, Tumor Necrosis Factor-a 30, insulin 30, Prostaglandin 30, Calc carb 30, Interleukin 30, Pentosidine 30 , Glutamic acid 30 etc. These drugs could be used as single medicines or as combinations.
REDEFINING HOMEOPATHY 