Mayo Clinic Departments of Medicine, Physiology and Biomedical Engineering, and the Kogod Center on Aging, Rochester, MN, USA.
Mayo Clinic Departments of Medicine, Physiology and Biomedical Engineering, and the Kogod Center on Aging, Rochester, MN, USA.
Trends Mol Med. 2020 Jul;26(7):630-638. doi: 10.1016/j.molmed.2020.03.005. Epub 2020 Apr 17.
Cellular senescence is a primary aging process and tumor suppressive mechanism characterized by irreversible growth arrest, apoptosis resistance, production of a senescence-associated secretory phenotype (SASP), mitochondrial dysfunction, and alterations in DNA and chromatin. In preclinical aging models, accumulation of senescent cells is associated with multiple chronic diseases and disorders, geriatric syndromes, multimorbidity, and accelerated aging phenotypes. In animals, genetic and pharmacologic reduction of senescent cell burden results in the prevention, delay, and/or alleviation of a variety of aging-related diseases and sequelae. Early clinical trials have thus far focused on safety and target engagement of senolytic agents that clear senescent cells. We hypothesize that these pharmacologic interventions may have transformative effects on geriatric medicine.
细胞衰老（cellular senescence）是一种主要的衰老过程和肿瘤抑制机制，其特征为不可逆的生长停滞、抗凋亡、产生衰老相关分泌表型（SASP）、线粒体功能障碍，以及 DNA 和染色质改变。在临床前衰老模型中，衰老细胞的积累与多种慢性疾病和紊乱、老年综合征、多种疾病共存和加速衰老表型有关。在动物中，通过遗传和药理学手段减少衰老细胞负担可预防、延缓和/或减轻多种与衰老相关的疾病和后果。早期临床试验迄今为止主要集中在清除衰老细胞的细胞消融剂的安全性和靶点结合上。我们假设这些药物干预可能对老年医学产生变革性影响。
