This open access commentary reflects a reasonable conservative position on the development of means to treat aging, which is that nothing can yet produce greater and more reliable results in humans than undertaking a better lifestyle. In this view, some combination of aerobic exercise, strength training, and calorie restriction robustly does more for most people than any of the other options on the table. Ten years ago I would have agreed. Now, however, I think it clear that senolytic therapies to selectively destroy senescent cells and some forms of mesenchymal stem cell transplantation, those capable of produce a significant amount of engraftment of the transplanted cells, can achieve greater benefits than lifestyle choices. We would need to see more work on NAD+ upregulation and mitochondrially targeted antioxidants to make the same claim there, while much of the rest of the present field seems unlikely to ever do as well as lifestyle interventions.
In modern times, inventing a drug that prevents the aging-linked decline in organ function, expands the years of life spent in good health, or even increases lifespan promises fame and fortune for the discoverer. Vitamins, anti-oxidants, resveratrol and other alleged sirtuin activators, caloric restriction, nicotinamide adenine dinucleotide (NAD+) and its biosynthetic precursors, young blood and growth and differentiation factor 11 (GDF 11), senolytics, rapamycin and rapalogs, metformin as well as numerous other compounds and treatments all were (or still are) considered as the magic bullet for "anti-aging" effects in the last couple of years.
However, for most, if not all of them, preclinical results in animal models were difficult to translate to humans, unexpected adverse effects in animals or humans were reported, and/or clinical trials showing any efficacy in healthy young and old individuals are still elusive. Importantly, aging per se is not recognized as a disease, and so-called "anti-aging" effects are often difficult to disentangle from disease prevention. For example, it is not entirely clear whether the beneficial outcome of caloric restriction in non-human primates is due to a reduction of numerous diseases observed in control-fed primates (whatever control levels mean in a laboratory context for these animals), or if true "anti-aging" effects were achieved.
In stark contrast to the currently proposed putative "anti-aging" drugs, a combination of various lifestyle-based approaches clearly achieves the best epidemiological risk profile for healthy aging, with minimal or no adverse effects. Moreover, some of these approaches, for example exercise training, are not only highly efficient in preventing certain chronic diseases, but also in the treatment of numerous pathologies. While it is true that the molecular basis of the health beneficial effect of exercise remains largely enigmatic, for as long as data about clinical efficacy and safety of exercise "mimetics" and "anti-aging" drugs are missing (and probably even beyond that), lifestyle-based interventions remain the mainstay approach to minimize the risk for diseases, reduce morbidity and mortality and most importantly, improve healthspan in aging. The old adage "use it or lose it" should thus serve as a reminder that regular physical activity is directly and strongly linked to health in the young and the elderly.