Senotherapeutic Interventions Targeting Mitochondria

Healthy aging is a delicate balancing act. On one side of the scale are factors that hinder aging, and on the other are human efforts to combat these factors. Among them, the most important factor hindering aging is age-related diseases. Developing senotherapeutic strategies may provide effective solutions for patients with age-related diseases. Mitochondrial dysfunction is crucial in elucidating the pathogenesis of age-related diseases and providing suitable treatment options. Although mitochondrial dysfunction is a common feature of cellular aging, why mitochondrial dysfunction plays a central role in the formation of the senescence-associated secretory phenotype (SASP) associated with age-related diseases remains unclear. Mitochondrial dysfunction and SASP-related disease progression are closely related to declining immunity, a common phenomenon in the aging process.

A class of substances called senotherapeutics, which target senescent cells, can be divided into two major categories: senolytics (kill senescent cells) and senomorphics/senostatics (inhibit their SASP secretion), to extend healthspan and potential lifespan. Since mitochondria are also closely related to the survival of senescent cells, using either mitochondria-targeting senolytics or senomorphics with redox modulators may help us address the complex problems and harmful consequences of cellular senescence. Currently, killing senescent cells and/or mitigating the negative effects of their SASP is considered an effective mitochondria-targeting senotherapeutic approach against age-related diseases.