A Discussion of Current Approaches Under Development for the Treatment of Aging
This open access paper tours a number of the present approaches under development to the treatment of aging as a medical condition, dwelling the most on therapies targeting senescent cells, either for destruction or to suppress the harmful senescence-associated secretory phenotype. We live in an exciting time of great potential, an age of accelerating progress in the capabilities of medical biotechnology, though it remains the case that too few people realize just how close we are to the widespread use of the first practical rejuvenation therapies.
Aging poses one of the greatest challenges for modern medicine, as it is a major risk factor for chronic diseases such as cancer, cardiovascular and neurodegenerative diseases. As the global population continues to age, there is an urgent need to develop effective interventions and diagnostic tools to prevent illness and extend a healthy lifespan, thereby reducing the burden of age-related diseases on healthcare systems.
Most basic research on aging is focused on identifying mechanisms contributing to this trait. Several hallmarks/pillars of aging have been defined and summarize the main processes underlying aging. Although these definitions are still suboptimal, they provide a nice framework used by many groups in the field to define which aspects of aging their research is focused on. One approach is to target the driving mechanisms of aging, like impaired autophagy and senescence. Inactivation of the mTOR pathway by interventions such as dietary restriction or with small molecule inhibitors like rapamycin, results in autophagy de-repression and lifespan extension (in fruit flies, worms, and mice). Extensive data suggest that rapamycin and rapalogs may have positive effects on age-related conditions and possibly on human longevity.
Cellular senescence is another potentially druggable mechanism that has been much 'in focus' to try to prevent or treat many age-associated pathologies, including cardiovascular, cerebrovascular, neurodegenerative, metabolic, and malignant diseases. Accumulated senescent cells (SenC) have deleterious effects due to the induced proinflammatory microenvironment that supports chronic low-grade inflammation ('inflammaging') and possible tumor development, and accelerate other aging mechanisms which will progress concomitantly. The depletion of SenC in aged organisms, either via genetic ablation or pharmacologically with senolytics, may have therapeutic benefits by alleviating a series of age-associated comorbidities and thus improving healthspan and even lifespan, as shown in lower organisms.
By now, research and development in the biology of aging have moved to the mainstream with initiatives by large pharmaceutical companies and funds, highlighting the growing interest in geroscience and the development of interventional gerotherapeutics. On the financing side, players like Altos Labs and Hevolution have entered the field, looking to deploy massive amounts of capital to accelerate research and commercial product development. These initiatives reflect the increasing recognition of the potential commercial impact of anti-aging therapies on healthcare and society.