Introduction to Aging
A complex biological process, aging is defined by a slow deterioration in physiological and cellular processes. This raises susceptibility to illness and, eventually, death. Extrinsic environmental impacts and intrinsic genetic factors combine to cause aging, according to research. The basic mechanisms of aging are categorized into nine primary categories by López-Otín and colleagues' "Hallmarks of aging" paradigm. These categories include loss of proteostasis, telomere attrition, genomic instability, and epigenetic changes. Together, these characteristics explain how damage builds up in cells, reducing their capacity to perform at their best and, ultimately, the organism's long-term resilience.
Generally speaking, there are two types of theories about aging. Programmed theories, propose that aging occurs according to a genetic schedule, and stochastic theories, see aging as compounded random harm. Studies aiming to increase health span—the number of years spent in excellent health—rather than just longevity have been spurred by this understanding of aging.
Anti-Aging And Its Mechanism
Understanding and reducing the biological processes that cause age-related deterioration is the goal of anti-aging science. Although aging is not a disease in and of itself, it is intimately linked to several age-related illnesses. These include metabolic, neurological, and cardiovascular conditions. To strengthen cell repair systems, preserve cellular integrity, and boost immunological responses, anti-aging therapies focus on the cellular and molecular characteristics of aging. Such as genomic instability and telomere shortening. Calorie restriction is one anti-aging strategy that has been demonstrated to increase longevity in a variety of animals by enhancing metabolic functions and lowering oxidative damage. The ability to alter longevity-related genes to encourage a longer lifespan is another area of attention for developments in genetic and epigenetic research.
Different Approaches for Anti-Aging
In the search for anti-aging therapies, several strategies have been investigated. These include:
Pharmacological Agents
The possible anti-aging effects of several medications are being researched. In animal models, medications such as rapamycin and metformin have demonstrated promise in postponing aging markers and increasing longevity.
Primarily prescribed for type 2 diabetes, Metformin has been demonstrated to increase longevity in model organisms and is currently being investigated for its potential impact on disorders associated with aging. It improves mitochondrial function and lowers inflammation. (Barzilai et al., 2016).
Rapamycin, which inhibits the mTOR pathway and has been shown to prolong mouse lifespans, is another promising drug. It regulates cellular metabolism and promotes autophagy, a process by which cells break down and recycle damaged components, (Harrison et al., 2009).
Nutraceuticals and Dietary Supplements
Researchers are looking at the potential of compounds like resveratrol, curcumin, and NAD+ precursors (such as nicotinamide riboside) to increase lifespan and healthspan (Baur et al., 2006; Imai & Yoshino, 2013).
Lifestyle Modifications
An anti-aging strategy must include stress management skills, a balanced diet, and regular physical activity. According to O'Keefe et al. (2015), exercise has been associated with better cognitive function and a lower chance of developing chronic illnesses. Numerous studies have found that calorie restriction and intermittent fasting increase lifespan and improve cellular function in a variety of species. These treatments lessen inflammation and oxidative stress, two factors that contribute to aging.
Genetic and Cellular Interventions
New developments in stem cell therapy, gene editing, gene therapy and regenerative medicine have the potential to target cellular aging processes. Future anti-aging treatments may benefit from advances in gene editing, especially with CRISPR, which targets genes linked to cellular repair and longevity. Scientists want to create therapies that could have a major impact on the aging process by modifying genes that affect DNA repair, telomere length, and other aging markers.
Effectiveness of Anti-Aging Agents Based on Clinical Data
Individual reactions and the precise systems targeted determine the effectiveness of anti-aging medicines. Studies and clinical trials show encouraging outcomes for several interventions.
Metformin
The purpose of the TAME (Targeting Aging with Metformin) trial is to ascertain how well the medication works to prevent age-related illnesses and prolong a healthy life expectancy (Barzilai et al., 2017). According to preliminary research, there may be advantages in lowering the prevalence of age-related illnesses.
Rapamycin
Rapamycin has demonstrated positive benefits on immunological function in older persons in clinical investigations. This indicates that it may mitigate some aspects of immunosenescence (Mannick et al., 2018).
Nutraceuticals
Although preclinical research on resveratrol and other polyphenols has shown promise, human trials are still required to prove their effectiveness. Although results vary, a meta-analysis of resveratrol research indicated positive impacts on metabolic health (Timmers et al., 2011).
Lifestyle Interventions
Research continuously shows that dietary changes and physical exercise promote longevity and health outcomes, highlighting their significance in anti-aging tactics (Buchman et al., 2012).
AN OVERVIEW OF ANTI-AGING DRUGS
Disclaimer: The following information is for informational purposes only and should not be considered medical advice. This content is not intended to diagnose, treat, or practice medicine. Readers are encouraged to validate the information with healthcare professionals before any use.
1. Metformin
An oral antihyperglycemic drug called Metformin has been used extensively to treat type 2 diabetes. Due to its potential to increase healthspan and prolong longevity, it is the first-line treatment for this ailment and has drawn interest from the anti-aging research community. Metformin is well-known for its mode of action, which may affect the biological processes linked to aging in addition to helping regulate blood sugar levels.
Mechanism in Anti-Aging
Metformin activates an enzyme called AMPK (AMP-activated protein kinase). It is a crucial regulator of cellular energy homeostasis. As a result of activation, Insulin sensitivity rises and hepatic glucose output falls. The effects of metformin on AMPK may also improve autophagy, lower oxidative stress, and resemble some elements of calorie restriction—all of which are associated with longer lifespans and better health. (Zou et al., 2004).
Effectiveness Based on Clinical Data
Metformin may lower the incidence of age-related disorders, such as cardiovascular conditions and several types of cancer, according to several clinical investigations. By concentrating on its impact on age-related disorders, the ongoing TAME (Targeting aging with Metformin) study seeks to comprehensively evaluate the medication's ability to increase older persons' health span (Barzilai et al., 2016). Even while preliminary evidence appears encouraging, more investigation is required to draw firm conclusions.
Use and Benefits
Although its primary indication is the management of type 2 diabetes, metformin has demonstrated potential advantages beyond glycaemic control. Metformin is a versatile medication in the context of aging, as research has shown that it may also lessen the chance of acquiring certain malignancies, enhance cardiovascular health, and reduce inflammation.
Dosing
The doses will change depending on your condition and the purpose. Follow your doctor's or endocrinologist's advice. The typical dose for anti-aging is 500–2500 mg per day.
Indications
Type 2 diabetes mellitus
Polycystic ovary syndrome (PCOS)
Contraindications
Renal impairment (eGFR < 30 mL/min)
Metabolic acidosis
Side Effects
Gastrointestinal issues like nausea and diarrhoea are frequent side effects. Lactic acidosis is an uncommon but dangerous side effect that requires renal function to be monitored while on medication.
2. Resveratrol
Resveratrol is also known as “the red wine molecule”. It is a naturally occurring polyphenolic substance present in many plants but is especially abundant in red grapes, berries, and peanuts. Due to its antioxidant effects and capacity to activate specific pathways linked to lifespan, it has drawn a lot of attention for its alleged anti-aging qualities.
Mechanism in Anti-Aging
Sirtuins—proteins that control cellular stress response and enhance longevity—are known to be activated by resveratrol, especially SIRT1. Resveratrol may help reduce the biological impacts of aging by increasing sirtuin activity. This includes boosting autophagy and mitochondrial function (Baur et al., 2006). Resveratrol also replicates some of the effects of calorie restriction, which has been demonstrated to increase lifespan in a variety of organisms.
Effectiveness Based on Clinical Data
Although preclinical research in several model organisms has demonstrated encouraging findings on resveratrol's capacity to increase lifespan and enhance health, there still needs to be more information from human clinical trials, and the results are sometimes conflicting. A clinical study evaluated the effects of topical resveratrol on skin aging. As a potential topical anti-aging agent, the study showed that participants who used a resveratrol-infused cream over 12 weeks experienced significant improvements in skin elasticity, hydration, and overall appearance (Baxter et al., 2008).
Use and Benefits
Resveratrol is frequently promoted as an antioxidant-rich dietary supplement that may have positive effects on the heart. According to certain research, it may enhance endothelial function and reduce blood pressure, which could be advantageous for heart health.
Dosing
The dose employed in clinical trials differs greatly based on the particular results being assessed. Doses ranging from 100 mg to 1,000 mg daily have been used in numerous investigations. For example, a study that was published in "Cell Metabolism" found that subjects who took 1,000 mg of resveratrol every day for 12 weeks experienced improvements in metabolic health markers and insulin sensitivity.
Indications
Antioxidant support
Cardiovascular health promotion
Contraindications
Due to possible interactions, people using anticoagulant medicines are recommended to exercise caution. It could intensify the effects of blood thinners like warfarin, increasing the chance of bleeding.
Side Effects
Although generally regarded as safe, stomach distress is one of the frequent side effects. Blood-thinner interactions are possible and should be closely monitored.
3. Fosamax (Alendronate)
Alendronate, marketed under the name Fosamax, is a bisphosphonate drug mainly used to treat and prevent osteoporosis. It is essential for preserving bone health, particularly in aging populations and postmenopausal women, where fracture risk rises sharply.
Mechanism in Anti-Aging
By preventing osteoclast-mediated bone resorption, Fosamax preserves or improves bone density. Fosamax may help avoid fractures by strengthening bones, which would improve older persons' mobility and quality of life—two crucial components of good aging.
Effectiveness Based on Clinical Data
Clinical data demonstrate that Fosamax effectively reduces the risk of vertebral and hip fractures in postmenopausal women with osteoporosis. Long-term studies have shown sustained benefits in bone density and reduced fracture risk, which are critical for maintaining independence and quality of life in aging individuals. Bone density and aging have a crucial relationship. Alendronate may lessen the impacts of age-related bone loss, according to research. Alendronate may help prevent age-related osteoporosis, according to a study by McClung et al. (2001) that found it significantly increased bone mineral density (BMD) in older women.
Use and Benefits
Osteoporosis and Paget's disease of the bone can be prevented and treated with Fosamax. Its main advantage is that it lowers the chance of fractures, which is important for elderly people who are more likely to fall and suffer related problems.
Dosing
10 mg per day or 70 mg per week is the usual dose for Fosamax, depending on the patient's preferences and the doctor's orders.
Indications
Osteoporosis in postmenopausal women
Paget's disease of bone
Contraindications
People with hypocalcaemia or oesophagal anomalies that may make swallowing difficult should not use Fosamax.
Side Effects
Common side effects, especially following dental treatments, include gastrointestinal distress and, in rare instances, jaw osteonecrosis. Patients need to be watched for any indications of negative consequences.
4. Rapamycin
The mTOR (mechanistic target of rapamycin) inhibitor Rapamycin, sometimes called sirolimus, is mostly used as an immunosuppressant in organ transplantation. Its capacity to increase lifespan in a variety of model species has sparked considerable interest in its possible anti-aging activity.
Mechanism in Anti-Aging
By blocking the mTOR pathway, which is essential for controlling cell growth, proliferation, and survival, rapamycin has anti-aging benefits. Rapamycin increases cellular stress responses, decreases senescence, and stimulates autophagy by blocking mTOR, all of which may contribute to a longer lifespan and better health. (Harrison et al., 2009).
Effectiveness Based on Clinical Data
Rapamycin has been shown in preclinical trials to increase lifespan in mice, and research on its effects in humans is still underway. Although preliminary findings point to possible advantages in improving immune function in older persons (Mannick et al., 2018), more thorough clinical trials are required to prove safety and efficacy in aging populations.
Use and Benefits
Rapamycin is mainly prescribed to organ transplant recipients to avoid rejection. Enhancing longevity, lowering the incidence of age-related illnesses, and strengthening the immune system are some of its possible advantages as people age.
Dosing
Although rapamycin doses vary, research usually employs a weekly dose of 5-7 mg. The ideal doses for anti-aging effects are still being studied, though.
Indications
Organ transplant
Certain cancers
Contraindications
Patients with active infections and those who are hypersensitive to the medication should not take rapamycin.
Side Effects
An elevated risk of infections, metabolic abnormalities, and detrimental impacts on wound healing are examples of possible side effects. Throughout treatment, routine monitoring is advised.
5. GLP-1 Agonists
A class of drugs known as GLP-1 (glucagon-like peptide-1) agonists works by imitating the effects of the natural hormone GLP-1. It is involved in the metabolism of glucose. These medications include semaglutide (Ozempic, Wegovy) and liraglutide (Saxenda, Victoza). They are mostly used to treat type 2 diabetes and obesity. Their potential anti-aging effects, especially in enhancing metabolic health and lowering the risk of age-related illnesses, have drawn attention recently.
Mechanism in Anti-Aging
GLP-1 agonists function by blocking glucagon release, increasing insulin secretion in a glucose-dependent manner. This encourages satiety, which aids in appetite and weight control. In addition to enhancing glycaemic management, these pathways may also benefit metabolic syndrome and cardiovascular health, two important aspects of aging. GLP-1 agonists may lessen the impact of aging on metabolic health by encouraging weight loss and enhancing insulin sensitivity.
Effectiveness Based on Clinical Data
Clinical studies have consistently demonstrated that GLP-1 agonists lead to significant reductions in body weight and improvement in glycemic control. However, according to clinical evidence, they may also lessen oxidative stress, and systemic inflammation, and enhance cell signalling in organs like the brain, kidneys, and heart that are susceptible to aging-related harm. These agonists have been demonstrated to reduce oxidative stress and inflammatory biomarkers, which are prevalent in degeneration associated with aging. These results are corroborated by studies conducted on animal models. They indicate that GLP-1 therapies improve outcomes in neurodegenerative and cardiovascular disorders. This is especially important since metabolic dysregulation and inflammation hasten the aging process and the emergence of age-related disorders. More thorough, longitudinal clinical trials are required to fully understand its effects on aging.
Use and Benefits
GLP-1 agonists are primarily indicated for type 2 diabetes management and obesity treatment. Their benefits include significant weight loss, improved glycemic control, and potential cardiovascular protection. Some studies also suggest that GLP-1 agonists may positively impact liver health by reducing fat accumulation and inflammation, which is relevant for age-related conditions such as non-alcoholic fatty liver disease (NAFLD).
Dosing
Clinical trials exploring GLP-1 receptor agonists (GLP-1 RAs) for anti-aging applications primarily use dosing protocols similar to those used in diabetes and obesity treatments. For example, liraglutide is often started at a low dose, such as 0.6 mg daily, gradually increasing based on tolerance up to 1.8 mg daily. Semaglutide, another commonly studied GLP-1 RA, is typically dosed weekly, starting at 0.25 mg and increasing to 1 mg over several weeks.
Indications
Type 2 diabetes mellitus
Chronic weight management in obesity
Contraindications
Since these medications may raise the incidence of thyroid tumours, they are contraindicated in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Patients with a history of pancreatitis are also urged to exercise caution.
Side Effects
Gastrointestinal symptoms like nausea, vomiting, diarrhoea, and abdominal discomfort are typical side effects. Thyroid tumours and pancreatitis are adverse effects. Throughout treatment, patients should be watched for these side effects.
6. SGLT-2 Inhibitors
Empagliflozin (Jardiance), canagliflozin (Invokana), and dapagliflozin (Farxiga) are examples of SGLT-2 (sodium-glucose co-transporter 2) inhibitors. It is a class of drugs mostly used to treat type 2 diabetes. Their potential advantages for cardiovascular and renal health—two important aspects of aging—have just come to light.
Mechanism in Anti-Aging
SGLT-2 inhibitors increase glucose excretion in the urine by blocking the kidneys' ability to reabsorb glucose. This effect lowers blood pressure, encourages weight loss, and enhances glycaemic management. New research indicates that SGLT-2 inhibitors may protect the heart and enhance kidney function, both of which are vital for older adults who are more susceptible to these disorders. (Zinman et al., 2015).
Effectiveness Based on Clinical Data
According to clinical trials, SGLT-2 inhibitors considerably lower the incidence of heart failure hospitalizations and cardiovascular events in individuals with type 2 diabetes (Zinman et al., 2015). In patients with preexisting cardiovascular disease, empagliflozin improved renal outcomes and decreased the incidence of significant adverse cardiovascular events, according to the EMPA-REG OUTCOME trial. These results demonstrate how SGLT-2 inhibitors may help prolong life expectancy in older adults.
Use and Benefits
Although SGLT-2 inhibitors are mainly prescribed to treat type 2 diabetes, they also help people lose weight, lower their blood pressure, and enhance their cardiovascular and renal health. These medications are especially beneficial for elderly people with numerous comorbidities because they may also help lower the chance of developing chronic renal disease.
Dosing
Current research on SGLT-2 inhibitors for anti-aging uses the same doses as are often used to treat heart failure and diabetes because of their metabolic effects. In metabolic and cardiac studies, common SGLT-2 inhibitors such as canagliflozin and empagliflozin are usually given at 100–300 mg daily and 10–25 mg daily, respectively. Although these doses work well for metabolic illnesses, several anti-aging trials are still in their early phases, and dose modification might be necessary to maximize outcomes in older adults without metabolic comorbidities.
Indications
Type 2 diabetes mellitus
Heart failure (certain agents)
Chronic kidney disease (certain agents)
Contraindications
Severe renal impairment (eGFR < 30 mL/min) and a history of severe medication hypersensitivity are contraindications. Patients with a history of vaginal or urinary tract infections should also exercise caution.
Side Effects
Dehydration, hypotension, vaginal fungal infections, and urinary tract infections are typical adverse effects. Acute kidney damage and ketoacidosis are uncommon but dangerous adverse effects that can occur, especially in those with type 1 diabetes.
7. NAD+ Precursors (Nicotinamide Riboside and Nicotinamide Mononucleotide)
Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), two precursors of NAD+ (nicotinamide adenine dinucleotide), are attracting interest as possible anti-aging supplements. NAD+ is an essential coenzyme that plays a role in many cellular functions, such as cell signalling, DNA repair, and energy metabolism. NAD+ levels decrease with age, which may be a factor in several age-related illnesses.
Mechanism in Anti-Aging
The activity of sirtuins, a class of proteins that are important in controlling the longevity and health of cells, depends on NAD+. Precursors like NR and NMN may increase sirtuin activity by raising NAD+ levels, which would support metabolic health and cellular repair (Imai & Yoshino, 2013). Restoring NAD+ may also enhance energy metabolism and lower oxidative stress, which promotes healthy aging. NAD+ is also essential for mitochondrial activity.
Effectiveness Based on Clinical Data
NAD+ precursors have been demonstrated in preclinical research to efficiently raise NAD+ levels and enhance mitochondrial activity in a variety of organisms. Although there are currently few human clinical trials, early research suggests that NR supplementation may raise NAD+ levels in healthy individuals and enhance metabolic health indicators (Martens et al., 2018). To evaluate their effectiveness in older populations, more thorough long-term research is required.
Use and Benefits
The main application of NAD+ precursors is as dietary supplements to raise NAD+ levels. increased energy metabolism, greater exercise performance, increased cognitive function, and protection against age-related diseases are some possible advantages.
Dosing
Clinical research on the anti-aging properties of NAD+ precursors, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), has primarily concentrated on dosages that efficiently increase NAD+ levels to counteract age-related cellular deterioration.
In these investigations, NMN doses are usually given for weeks to months and vary from 250 to 500 mg daily. In older adults, these doses have been demonstrated to enhance vascular health, insulin sensitivity, and physical endurance.
Effective anti-aging doses for NR typically fall between 300 and 500 mg daily. According to clinical investigations, NR supplementation lowers inflammation, enhances mitochondrial health indicators, and may prevent cognitive deterioration.
Both NMN and NR efficiently raise blood NAD+ levels, but further research is required to identify the best, long-term dosages for anti-aging effects in a range of people.
Indications
Age-related decline in NAD+ levels
Support for metabolic health
Potential cognitive enhancement
Contraindications
There aren't any well-established contraindications at the moment, although people who are hypersensitive to niacin or similar substances should use these cautiously.
Side Effects
In general, NAD+ precursors are well tolerated. Some people could have slight flushing or gastrointestinal discomfort. The risk profile of these supplements cannot yet be completely described without long-term safety evidence.
8. Senolytics (Dasatinib and Quercetin)
Quercetin and Dasatinib were two of the first medications to be discovered to have senolytic qualities. This means they remove senescent cells from the body specifically. Damaged cells called senescent cells build up over time and are a contributing factor to chronic inflammation and aging. Together, quercetin, an antioxidant-rich plant flavonoid, and Dasatinib, a tyrosine kinase inhibitor and cancer medication, cause these senescent cells to undergo apoptosis. Because of their complementary effects, Dasatinib and Quercetin work especially well together to remove senescent cells from tissues including the heart and lungs.
Mechanism in Anti-Aging
Dasatinib mainly works by blocking particular tyrosine kinases that are part of processes that encourage cellular senescence. Senescent cells undergo apoptosis, or programmed cell death, as a result of this inhibition. By modifying the SASP, a group of inflammatory cytokines released by senescent cells, Quercetin enhances this effect. Quercetin can reduce inflammation and possibly restore tissue function by lowering these variables (Zhu et al., 2015).
Reduction in Senescence-Associated β-Galactosidase
One important biomarker of cellular senescence that is used to identify aging cells is senescence-associated β-galactosidase (SA-β-gal). Studies show that SA-β-gal activity in tissues is markedly reduced in humans and animals when Dasatinib and Quercetin are administered intermittently. D&Q may help restrict the cellular "aging" markers associated with age-related tissue degeneration and organ failure by lowering SA-β-gal expression.
Suppression of Pro-Inflammatory SASP Genes
SASP are a group of pro-inflammatory cytokines, chemokines, and proteases secreted by senescent cells. They contribute to inflammation, tissue deterioration, and age-related illnesses such as arthritis, heart disease, and dementia. It has been demonstrated that D&Q reduces systemic inflammation and may lessen the consequences of low-grade, chronic inflammation linked to aging by downregulating the expression of SASP genes. D&Q treatment reduced the expression of pro-inflammatory SASP factors, such as IL-6, IL-8, and TNF-α, which are important participants in inflammatory processes, in elderly mice, according to a 2018 study published in Nature Medicine.
Effectiveness Based on Clinical Data
According to studies conducted in mouse models, Dasatinib and quercetin can dramatically lower the load of senescent cells, improving organ function and lowering age-related diseases like osteoporosis and frailty. Although research on humans is still in its early stages, initial findings indicate that this combination may enhance older persons' physical function and quality of life. (Gonzalez et al., 2022).
In human pilot trials, D&Q has demonstrated promise in reducing physical frailty markers and improving outcomes in age-related illnesses and diseases, such as idiopathic pulmonary fibrosis (IPF), which has a large concentration of senescent cells (J. N. et al., 2019). Mice administered D&Q showed improvements in physical function, tissue renewal, and a decrease in age-related muscle degeneration. These results lend credence to the idea that D&Q, by eradicating senescent cells and reducing the associated inflammatory burden, may offer a novel treatment for age-related illnesses.
According to recent studies, rats exposed to overtraining stress—a condition known to promote cognitive decline through cellular senescence in the hippocampus—were demonstrated to be protected against learning and memory deficits by Dasatinib and Quercetin (D&Q). An increase in senescent and apoptotic cells in the hippocampus, a region essential for memory and learning, has been linked to overtraining. By lowering the quantity of senescent and apoptotic cells in the hippocampus, it was discovered that combined D&Q treatment mitigated these deficiencies and supported a more favourable cellular environment for cognitive performance. Since the elimination of senescent cells preserved brain structures and enhanced cognitive results in the stressed animals, the senolytic qualities of D&Q seem to be essential to this protective impact. This study demonstrates how D&Q may help treat cognitive deficits linked to cellular aging and stress-induced brain senescence (Wang et al., 2023). According to a Thomas Jefferson University study, giving this mixture to aging mice once a week for an extended period resulted in a notable decrease in inflammatory markers and cellular senescence in the disc tissue, preserving the disc's structure and functionality. This implies that using dasatinib and quercetin to target senescent cells may help postpone or avoid degenerative disc disorders, which are common in older adults.
In another study, administering D&Q to aging mice once a week for an extended period resulted in a notable decrease in inflammatory markers and cellular senescence in the disc tissue, preserving the disc's structure and functionality. This implies that using dasatinib and quercetin to target senescent cells may help postpone or avoid degenerative disc disorders, which are common in older adults (Novais et al., 2021).
Use and Benefits
Enhanced tissue regeneration, increased metabolic efficiency, and a decrease in systemic inflammation are the main expected advantages of utilising these senolytics. Clinical trials are still being conducted because of their potential to slow down age-related decline, even if they have not yet received approval for anti-aging uses.
Dosing
Dasatinib and Quercetin have shown promise in anti-aging therapies with intermittent dosing regimens to limit toxicity. In clinical trials, a dose of Dasatinib (100 mg) and Quercetin (1000 mg) administered over two consecutive days weekly has reduced senescent cells and improved physical function in older adults. Animal studies with biweekly doses (Dasatinib 5 mg/kg and Quercetin 50 mg/kg) have also shown efficacy in reducing age-related markers.
Indications
Indications for Dasatinib and Quercetin include lowering cellular senescence, enhancing cognitive and physical performance, and controlling chronic inflammation. Their entire potential to promote healthy aging will be shown by ongoing clinical trials and additional studies.
Contraindications
To reduce the chance of negative reactions, people on anticoagulant medication or those who have a history of ingredient hypersensitivity should stay away from these products.
Side Effects
Anaemia, diarrhoea, dermatitis, and low blood cell counts are some of the adverse effects of the cancer medication Dasatinib. Serious adverse effects include cardiac failure, pulmonary oedema, haemorrhage, and extended QT syndrome can potentially result from it. Fatigue, gastrointestinal issues, and headache are possible side effects of Quercetin. To prevent complications, especially in elderly populations, monitoring is essential.
9. Fisetin
Fisetin is a naturally occurring flavonoid that can be found in many fruits and vegetables, including onions, apples, and strawberries. Its broad range of anti-inflammatory and antioxidant qualities has drawn attention, raising the possibility that it could help prolong life and slow down age-related deterioration.
Mechanism in Anti-Aging
Fisetin has been demonstrated to alter several important biological processes linked to aging and cause senescent cells to undergo apoptosis. It reduces inflammation and improves cellular metabolism by activating AMPK and inhibiting the NF-κB pathway (Kirkland et al., 2017). Its possible neuroprotective and anti-inflammatory benefits are a result of these actions.
Effectiveness Based on Clinical Data
In preclinical studies, Fisetin demonstrated neuroprotective properties by drastically lowering inflammation and oxidative stress in aging brain tissues. Fisetin's potential to mitigate neurodegenerative changes associated with aging is supported by research conducted in old mice and caenorhabditis elegans models (a nematode worm - frequently used as a model organism in biological research on the immune system and aging). They showed reductions in inflammation, neuronal damage, and cognitive decline (Elsallabi et al., 2022). Early human trials suggest that it may improve memory and cognitive performance, although larger, more rigorous studies are needed to confirm these findings.
Use and Benefits
Fisetin is a candidate for additional research in age-related cognitive decline and other inflammatory disorders because of its potential benefits. These include neuroprotection, enhanced cognitive health, decrease in chronic inflammation and anti-oxidation.
Dosing
According to clinical studies looking into Fisetin's anti-aging properties, a dose of about 20 mg/kg of body weight should be taken twice a month. This would be equivalent to roughly 1,400 mg daily for a 155-pound adult. Given Fisetin's possible effects on senescent cell clearance, it is advised that this dose be taken sporadically, such as a few days per month, rather than as a daily maintenance dose. Because of its limited bioavailability, it is frequently combined with lipids to enhance absorption. Even while fisetin supplements of 100–500 mg are frequently used regularly, studies employ these larger levels with caution, highlighting the need for additional information on long-term safety and effectiveness .
Indications
Fisetin may help manage age-related ailments including cognitive decline and lessen the symptoms of inflammation-related diseases like osteoarthritis. Furthermore, fisetin has been investigated for its ability to improve metabolic health, namely in glucose metabolism, which may make it beneficial for metabolic diseases like diabetes. However, more thorough clinical research is needed to determine the safety profile and conclusive indications.
Contraindications
Fisetin is generally seen to be safe, although people who are taking anticoagulants or have a history of flavonoid allergies should be cautious.
Side Effects
The most frequent side effects of Fisetin are moderate allergic responses and gastrointestinal discomfort, which are generally easily tolerated.
10. Human Growth Hormone (HGH)
The pituitary gland produces a peptide hormone known as human growth hormone (HGH). It is essential for metabolism, body composition, and growth. Beyond growth inadequacies, it is being used to treat anti-aging conditions. However, this use is debatable and still being studied.
Mechanism in Anti-Aging
Human Growth Hormone (HGH) promotes cell regeneration, protein synthesis, and tissue repair, all of which have anti-aging effects. It functions by promoting insulin-like growth factor 1 (IGF-1), which supports bone density, muscle mass, and skin thickness—all of which tend to decrease with age. Additionally, HGH encourages lipolysis, which helps reduce fat and may increase energy levels. Even though HGH replacement therapy has improved older persons' body composition and physical function, its usage is still debatable because of adverse effects including insulin resistance, oedema, and joint discomfort. Therefore, while contemplating HGH as an anti-aging medication, medical supervision is essential. To completely comprehend the long-term effects of aging, more studies are still being conducted (Tresguerres et al., 2022).
Effectiveness Based on Clinical Data
Clinical data on HGH for anti-aging are mixed. Results from clinical studies on human growth hormone's (HGH) anti-aging efficacy have been conflicting. HGH treatment was linked to a slight increase in lean body mass and a decrease in fat mass in a systematic evaluation of trials involving older persons without growth hormone insufficiency. However, it did not affect muscle strength or general physical function. These advantages did, however, come with a higher risk of side effects, such as insulin resistance, carpal tunnel syndrome, joint discomfort, and oedema, which in some situations elevated the risk of type 2 diabetes. Furthermore, several studies did not find a significant increase in life expectancy or functional mobility, and there are some signs that HGH may worsen rather than slow down age-related problems. The variability in outcomes may be attributable to differences in study design, dosing, and patient populations. Numerous doctors advise against using HGH as a primary anti-aging treatment due to its substantial adverse effects and unclear advantages. To elucidate its function and safety in the elderly population, further extensive research is required (Bartke, 2019).
Use and Benefits
Despite its controversial nature, HGH is frequently promoted for its ability to improve older persons' physical performance, vitality, and quality of life. It is primarily prescribed for growth hormone deficiency.
Dosing
Clinical research indicate that a mean treatment dose of approximately 14 µg/kg per day over 27 weeks is recommended for anti-aging purposes. The usual dose of human growth hormone (HGH) is between 2 and 3 International Units (IU) per day. These doses are linked to adverse consequences like oedema and glucose intolerance, even though they have been found to increase lean body mass and decrease fat. Because of the possible health hazards, careful monitoring is essential. To determine the best dose and safety profiles, more research is required.
Indications
For disorders associated with growth hormone insufficiency, HGH is recommended. The medical world is still debating and mostly opposing its usage for anti-aging objectives.
Contraindications
Patients with extreme obesity, respiratory failure, or active cancers should not take HGH because hormone therapy can make these diseases worse.
Side Effects
Joint discomfort, insulin resistance, and an elevated risk of diabetes are typical adverse effects. Concerns regarding possible cardiovascular problems and the risk of cancer are raised with prolonged use.
11. Metabolic Enhancers (AICAR and Pterostilbene)
AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide) is an AMPK activator. Pterostilbene is a naturally occurring substance that shares structural similarities with resveratrol. Both substances are being researched for their potential to improve metabolism and prevent aging.
Mechanism in Anti-Aging
AMP-activated protein kinase (AMPK) is triggered by AICAR. It is an important modulator of cellular energy homeostasis that supports mitochondrial activity and metabolic health. It is essential for cellular deterioration brought on by aging. Further reducing age-related degeneration, this activation enhances insulin sensitivity, and lipid metabolism, and can trigger autophagy (Ruiz et al., 2016). Pterostilbene is a naturally occurring polyphenol. It has been demonstrated to enhance metabolic health by activating the AMPK and SIRT1 pathways and exhibiting antioxidant qualities that protect against oxidative stress. It may have preventative effects against age-related disorders because of its higher bioavailability than resveratrol, which enables better absorption and effectiveness (Liu et al., 2020). When combined, these substances offer encouraging treatment options for age-related metabolic decline.
Effectiveness Based on Clinical Data
Numerous clinical investigations have confirmed the anti-aging efficacy of pterostilbene and AICAR. AICAR has shown promise in metabolic control and muscle health due to its function in stimulating AMP-activated protein kinase (AMPK). AICAR may help prevent age-related decline in older persons by improving metabolic parameters and improving exercise performance, according to a clinical investigation (Liu et al., 2020).
A naturally occurring substance that is linked to resveratrol, pterostilbene, has drawn notice for its anti-inflammatory and antioxidant qualities. Clinical studies have demonstrated that pterostilbene can enhance metabolic and cardiovascular biomarkers. One study found that participants using pterostilbene experienced notable improvements in their lipid profiles and a significant decrease in blood pressure. Additionally, more effective dosing is possible due to its higher bioavailability than resveratrol.
Overall, even though pterostilbene and AICAR exhibit promise as metabolic enhancers in the setting of aging, more study is required to completely determine their efficacy and safety profiles in a range of groups.
Use and Benefits
These drugs are appealing candidates for more research in age-related disorders because of their potential advantages. These include increased physical endurance, improved metabolic health, and neuroprotective effects.
Dosing
AICAR has been administered in human trials at doses ranging from 5 to 25 mg/kg body weight, with an emphasis on enhancing insulin sensitivity and muscle metabolism, especially in older adults. Daily doses of pterostilbene have been investigated ranging from 50 mg to 250 mg/day. The higher dosage of 250 mg/day has shown encouraging results in improving metabolic health without causing notable side effects. Although more study is required to improve dosage guidelines and assess long-term safety, both substances show promise in reducing age-related metabolic decline.
Indications
Their effectiveness in treating metabolic problems, cognitive decline, and other age-related diseases is still being studied.
Contraindications
AICAR is mostly contraindicated in patients with renal impairment because of the way the kidneys metabolize and eliminate it. Pterostilbene may alter blood coagulation. Its usage should be handled carefully in patients on anticoagulants or antiplatelet drugs. Additionally, women who are pregnant or nursing should not use it because there is not enough safety information available for these populations. It is advised to speak with a healthcare professional before using pterostilbene because it may interact with other drugs, notably those that are metabolised by the liver.
Side Effects
Side effects associated with AICAR include decreased blood flow, which could result in problems with the heart valves and less blood reaching the brain. Mild hypoglycemia, lactic acid accumulation, diarrhoea, and increased thirst are further side effects that have been recorded. Although pterostilbene is thought to be safe, some users may experience headaches, dizziness, and gastrointestinal distress.
12. Telomerase Activators
The goal of telomerase activators is to preserve telomere length, which may postpone cellular aging. With every cell division, the protecting telomeres at the ends of chromosomes shrink, causing senescence and heightened vulnerability to illness. An example of this is TA-65. The Astragalus membranaceus plant is the source of the natural supplement TA-65. It is well-known for its ability to activate telomerase, an enzyme that lengthens telomeres, the protective structures at the ends of chromosomes. Telomeres shrink, causing cells to age and lose their ability to regenerate. By preserving or perhaps lengthening telomeres, TA-65 seeks to thwart this process, promoting cellular health and possibly delaying some age-related alterations. According to research, TA-65 may support healthy aging outcomes, enhance immunological function, and increase cellular longevity.
Mechanism in Anti-Aging
Telomerase, an enzyme that lengthens and repairs telomeres—the DNA sequences that shield chromosomal ends—is thought to be activated by TA-65, slowing down the aging process. With every cell division, telomeres naturally get shorter, causing senescence and cellular aging. Telomerase activation by TA-65 contributes to telomere length restoration, enhancing genomic stability and prolonging cellular life. Research has indicated that TA-65 may play a part in slower cellular deterioration and good aging by lowering the percentage of cells with critically short telomeres (de Jesus et al., 2011).
Effectiveness Based on Clinical Data
A study assessed the effect of TA-65 on telomere length and immune cell health in a placebo-controlled trial. The study, which lasted 12 months, recruited 117 adults between the ages of 53 and 87. Comparing participants in the TA-65 group to those in the placebo group, telomere elongation was significantly greater, indicating that TA-65 may be able to slow down telomere shortening, which is a symptom of cellular aging. Furthermore, it was discovered that TA-65 increased the percentage of cells with longer telomeres, which may be associated with enhanced cell longevity and function.
Another important study measured the effects of TA-65 on senescent T cells (CD8+CD28-), which tend to rise with age. They are associated with deteriorating immunity. The purpose was to investigate its involvement in immunological regulation. Participants in this randomised, placebo-controlled study of 500 healthy people showed a significant decrease in senescent T cells when compared to the placebo group, indicating that TA-65 may help older persons' immune systems (Singaravelu et al., 2021).
Use and Benefits
Telomerase activators are a topic of interest in anti-aging research because of their potential benefits. These include increased cellular longevity, higher regenerative ability, and a decrease in aging indicators.
Dosing
Since there is currently no defined standard regimen for telomerase activators, dosing techniques are constantly being investigated.
Indications
The roles of these activators in age-related illnesses, such as cardiovascular disorders, are still being investigated. Ideal for elderly people whose immune systems are deteriorating.
Contraindications
Not advised for anyone at risk for cancer. If utilising telomerase activators for an extended period, regular cancer screenings are advised.
Side Effects
Insufficient information on long-term side effects; more study is required. Rashes, mild headaches, and stomach discomfort are typical minor side effects in clinical studies.
One significant worry is that, although telomerase activation helps prolong telomeres, it may also raise the risk of cancer since it may encourage cell proliferation. More study is required to fully evaluate the long-term effects, but the majority of studies to date have not shown an increased risk of cancer among users.
CONCLUSION
To sum up, ongoing discoveries in anti-aging research present encouraging avenues for extending life expectancy and postponing age-related illnesses. Current studies show promise in improving cellular function and reducing the consequences of aging using a variety of therapies, including lifestyle changes, nutraceuticals, genetic methods, and pharmaceutical drugs such as Metformin and Rapamycin. Despite obstacles, research on medications that target particular aging processes shows promise in model species, with some signs of success in humans. It provides benefits such as better metabolic health, decreased inflammation, and longer lifespans. To fully comprehend the range of these treatments and create safe, efficient guidelines for their use, more research and clinical trials are essential.
FUTURE PROSPECTS
Anti-aging research has an exciting future because of several new treatments that try to slow down or even reverse ageing at the cellular level. While telomerase activators like TA-65 may provide strategies to preserve telomere length and increase cellular lifespan, senolytic medicines like dasatinib and quercetin have the potential to eliminate senescent cells, lower inflammation, and restore tissue health. By enhancing cellular resilience and encouraging autophagy, metabolic modulators such as metformin and rapamycin may significantly reduce age-related illnesses. In a similar vein, NAD+ precursors such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are being investigated for their potential to enhance DNA repair, increase cellular energy levels, and lower oxidative stress—all of which are essential for maintaining youthfulness in ageing cells.
Lifestyle changes like calorie restriction, intermittent fasting, and dietary nutraceuticals (like resveratrol and curcumin) continue to be important components of anti-aging therapies in addition to pharmaceutical approaches because of their positive effects on cellular function and the decrease of oxidative damage. With the capacity to directly alter aging-related genes and replace damaged cells, gene-editing technologies like CRISPR and stem cell-based regenerative therapies offer a vision for customised anti-aging therapy. With these developments, anti-aging treatments could soon integrate dietary, pharmacological, cellular, and genetic strategies based on each person's unique biological profile, providing a more comprehensive method of increasing longevity and healthspan.
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