Senolytics as a Treatment for Aging and Immunosenescence

Senolytic drugs capable of selectively destroying senescent cells in aged tissues are probably the most immediately promising of present efforts to treat aging as a medical condition. It is unfortunate that so little work presently takes place to rigorously evaluate the well established low-cost generic drug and supplement senolytics in human patients, as the animal studies suggest that they could be very beneficial. Unfortunately the high costs of running clinical trials ensure that low cost treatments receive little attention from the biotech and pharmaceutical industry. The dasatinib and quercetin combination is at least demonstrated to reduce the burden of senescent cells in humans, and is prescribed off-label by some anti-aging physicians, but large clinical trials are needed to be able to say in certainty that human use produces some degree of rejuvenation.

Aging is a multifactorial process driven by various intrinsic and extrinsic factors, including genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These factors are closely related to organismal aging, and research has shown that inducing them can accelerate aging, while intervening in them can slow down, halt, or even reverse the aging process.

Among these factors, cellular senescence is a key contributor to organismal aging. Targeting senescent cells (SCs) holds promise for developing novel and practical anti-aging therapies. Cellular senescence is an irreversible state of cell cycle arrest caused by various factors, such as DNA damage and telomere shortening. Additionally, the process whereby immune system function gradually declines or becomes dysregulated with human aging is known as immunosenescence. Although considerable variability in aging exists among individuals, the aging process generally involves chronic inflammation, tissue homeostasis disorders, and dysfunction of the immune system and organ functions, readily causing cardiovascular, metabolic, autoimmune, and neurodegenerative diseases associated with aging.

Existing research indicates that transplanting SCs into young mice induces bodily dysfunction, while transplanting them into aged mice exacerbates aging and increases the risk of death. This suggests that SCs accelerate organismal aging. The specific reason is that SCs release the senescence-associated secretory phenotype (SASP) into the tissue, promoting chronic inflammation and inducing senescence in surrounding tissue cells and immune cells. SCs and chronic inflammation interact and crosstalk, forming a vicious cycle of inflammation and aging. Therefore, in-depth research into the key characteristics and underlying mechanisms of cellular senescence, immunosenescence, and inflammation, identifying drug intervention targets, and developing targeted interventions can help mitigate aging and aging-related diseases, thereby promoting healthy aging in the elderly.