Anti-Aging

The objective of anti-aging medicine is to decelerate the aging process and mitigate its associated effects, such as susceptibility to cancer, diabetes, and cardiovascular and neurodegenerative diseases. ^[1] Geroprotectors are compounds that slow down aging and promote healthy longevity in model animals. ^[2] Aging is a physiological process mediated by numerous biological and genetic pathways that are directly linked to lifespan and are a driving force for all age-related diseases. ^[3]

Aging is closely associated with telomere attrition, DNA damage, mitochondrial dysfunction, loss of NAD+ levels, impaired macro-autophagy, stem cell exhaustion, inflammation, loss of protein balance, deregulated nutrient sensing, altered intercellular communication, and dysbiosis, and these age-related changes may be alleviated by intervention strategies. ^[4] Potential geroprotectors can be classified by mechanism into groups including those that prevent oxidation, proteostasis regulators, suppressors of genomic instability, epigenetic drugs, those that preserve mitochondrial function, inhibitors of aging-associated signaling pathways, senolytics, and anti-inflammatory drugs. ^[2] Six important signal pathways are critical in aging, including the mechanistic target of rapamycin, AMP-activated protein kinase, the nutrient signal pathway, SIRT1, regulation of telomere length, and energy metabolism, and are targeted by drugs such as rapamycin, metformin, acarbose and NAD+. ^[5]

Human life expectancy has greatly increased in the past few decades, but this has not been accompanied by a similar increase in healthspan. ^[3] There are reasonable expectations that drugs able to decelerate or reverse aging processes will also exert broad disease-preventing or disease-attenuating effects. ^[6] Calorie-restriction mimetics such as the AMPK activator metformin and the mTOR inhibitor rapamycin are among the lifestyle and pharmaceutical strategies studied to delay aging and related diseases. ^[1]

Eight promising drugs and natural compounds have been tested in the clinic for anti-aging effects: metformin, NAD+ precursors, glucagon-like peptide-1 receptor agonists, TORC1 inhibitors, spermidine, senolytics, probiotics, and anti-inflammatories. ^[6] Although hundreds of compounds have been shown to extend the life of laboratory model organisms, clinical studies on potential geroprotectors are exceedingly rare, especially in healthy elders. ^[2] Drugs approved for specific disease indications may subsequently be repurposed for the treatment of organism-wide aging consequences. ^[6] There is a large influx of NMN-based anti-aging products on the market, and proper clinical investigations are urgently needed to find out the effectiveness and safety of such supplementation. ^[7]