Department of Clinical Research, Copenhagen University Hospital, Amager and Hvidovre, Hvidovre, Denmark.
Adv Protein Chem Struct Biol. 2023;136:217-247. doi: 10.1016/bs.apcsb.2023.02.020. Epub 2023 Jun 8.
The accumulation of senescent cells in the aging individual is associated with an increase in the occurrence of age-associated pathologies that contribute to poor health, frailty, and mortality. The number and type of senescent cells is viewed as a contributor to the body's senescence burden. Cellular models of senescence are based on induction of senescence in cultured cells in the laboratory. One type of senescence is triggered by mitochondrial dysfunction. There are several indications that mitochondria defects contribute to body aging. Senotherapeutics, targeting senescent cells, have been shown to induce their lysis by means of senolytics, or repress expression of their secretome, by means of senomorphics, senostatics or gerosuppressors. An outline of the mechanism of action of various senotherapeutics targeting mitochondria and senescence-associated mitochondria dysfunction will be here addressed. The combination of geroprotective interventions together with senotherapeutics will help to strengthen mitochondrial energy metabolism, biogenesis and turnover, and lengthen the mitochondria healthspan, minimizing one of several molecular pathways contributing to the aging phenotype.
衰老个体中衰老细胞的积累与年龄相关病理的发生增加有关，这些病理导致健康状况不佳、虚弱和死亡。衰老细胞的数量和类型被视为身体衰老负担的一个因素。衰老的细胞模型是基于在实验室中培养细胞中诱导衰老。一种类型的衰老由线粒体功能障碍引发。有几个迹象表明线粒体缺陷导致身体衰老。针对衰老细胞的衰老治疗已被证明可以通过衰老细胞裂解剂诱导其裂解，或者通过衰老模拟物、衰老抑制剂或衰老抑制剂抑制其分泌组的表达。本文将介绍针对线粒体和与衰老相关的线粒体功能障碍的各种衰老治疗剂的作用机制。将抗衰老干预措施与衰老治疗相结合，将有助于加强线粒体能量代谢、生物发生和周转，并延长线粒体健康寿命，从而最大限度地减少导致衰老表型的几种分子途径之一。
