Longevity has always been a matter of interest, but absent an earnest scientific endeavor focused on intervention in aging it remained in the realm of fantasy, fraud, and futile wishes. That scientific endeavor was late in arriving, this delay largely the result of a cultural battle spanning the late 20th century that took place between the founders of modern anti-aging clinical practices and supplement industry companies on the one side versus the aging research community on the other. Only over the last thirty years has a scientific community finally emerged to earnestly and openly focus on treating aging as a medical condition.
The pursuit of youth and longevity has accompanied human societies for millennia, evolving from mythological and esoteric traditions toward a scientific understanding of aging. Early concepts such as Greek ambrosia, Taoist elixirs, and medieval "aqua vitae" reflected symbolic or spiritual interpretations. A major conceptual transition occurred between the late nineteenth and early twentieth centuries, when aging began to be framed as a biological process. Pioneering ideas by Metchnikoff, together with early and sometimes controversial attempts such as Voronoff's grafting experiments, marked the first efforts to rationalize aging scientifically. In the mid-twentieth century, discoveries including the Hayflick limit, telomere biology, oxidative stress, and mitochondrial dysfunction established gerontology as an experimental discipline.
Contemporary geroscience integrates these insights into a coherent framework linking cellular pathways to chronic disease risk. Central roles are played by nutrient-sensing networks such as mTOR, AMPK, and sirtuins, together with mitochondrial regulation, proteostasis, and cellular senescence. Interventions, including caloric restriction, fasting-mimicking diets, rapalogues, sirtuin activators, metformin, NAD+ boosters, senolytics, and antioxidant combinations such as GlyNAC, show consistent benefits across multiple model organisms, with early human trials reporting improvements in immune function, mitochondrial activity, and biomarkers of aging. Recent advances extend to epigenetic clocks, multi-omic profiling, gender-specific responses, and emerging regenerative and gene-based approaches. Overall, the evolution from historical elixirs to molecular geroscience highlights a shift toward targeting aging itself as a modifiable biological process and outlines a growing translational landscape aimed at extending healthspan and reducing age-related morbidity.
Link: https://doi.org/10.3390/molecules30244728
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