Senolytics are drugs and other therapeutics that kill senescent zombie cells and activate autophagy, the natural mechanism whereby we clear senescent cells from our bodies. Autophagy (literally self-digesting) is an essential mechanism that is taking place every second of our lives. But as we age, we accumulate greater populations of senescent cells, and the natural process of senolysis is inhibited. Our modern lifestyles of overabundance of nutrients inhibits the natural activation of autophagy and leads to greater and greater numbers of senescence cells. Adiposity, and in in particular visceral adiposity, are the hallmarks of an inhibited system of autophagy.
The resultant life-long accumulation of senescent zombie cells causes the over expression of what is known as the senescence associated secretory phenotype, or SASP, which means that these senescent cells are actively secreting toxic compounds that not only poison our cellular well, these SASP cells actively recruit neighboring cells to become senescent, thereby increasing the burden of senescent cells in our bodies, further driving the progression of age-related diseases. Therefore, the process of Zombie cell autophagy and the therapeutic use of senolytics to accelerate senolysis is the subject of of a growing segment of scientific research dedicated to the enhancement of our natural longevity pathways.
Senotherapeutics: emerging strategy for healthy aging and age-related disease. Kim EC, Kim JR. BMB Rep. 2019 Jan;52(1):47-55. doi: 10.5483/BMBRep.2019.52.1.293. PMID: 30526770; PMCID: PMC6386227.
“Cellular senescence (CS) is one of hallmarks of aging and accumulation of senescent cells (SCs) with age contributes to tissue or organismal aging, as well as the pathophysiologies of diverse age-related diseases (ARDs). Genetic ablation of SCs in tissues lengthened health span and reduced the risk of age-related pathologies in a mouse model, suggesting a direct link between SCs, longevity, and ARDs. Therefore, seno- therapeutics, medicines targeting SCs, might be an emerging strategy for the extension of health span, and prevention or treatment of ARDs. Senotherapeutics are classified as senolytics which kills SCs selectively; senomorphics which modulate functions and morphology of SCs to those of young cells, or delays the progression of young cells to SCs in tissues; and immune-system mediators of the clearance of SCs. Some senolytics and senomorphics have been proven to markedly prevent or treat ARDs in animal models. “
First-in-human trial of senolytic drugs encouraging
Small pilot study points to feasibility of larger trials in age-related diseases