Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Department of Biology, Orentreich Foundation for the Advancement of Science, Cold Spring, New York.
Ann N Y Acad Sci. 2018 Apr;1418(1):31-43. doi: 10.1111/nyas.13549. Epub 2018 Jan 24.
The goal of the aging field is to develop novel therapeutic interventions that extend human health span and reduce the burden of age-related disease. While organismal aging is a complex, multifactorial process, a popular theory is that cellular aging is a significant contributor to the progressive decline inherent to all multicellular organisms. To explore the molecular determinants that drive cellular aging, as well as how to retard them, researchers have utilized the highly genetically tractable budding yeast Saccharomyces cerevisiae. Indeed, every intervention known to extend both cellular and organismal health span was identified in yeast, underlining the power of this approach. Importantly, a growing body of work has implicated the process of autophagy as playing a critical role in the delay of aging. This review summarizes recent reports that have identified a role for autophagy, or autophagy factors in the extension of yeast life span. These studies demonstrate (1) that yeast remains an invaluable tool for the identification and characterization of conserved mechanisms that promote cellular longevity and are likely to be relevant to humans, and (2) that the process of autophagy has been implicated in nearly all known longevity-promoting manipulations and thus represents an ideal target for interventions aimed at improving human health span.
衰老领域的目标是开发新的治疗干预措施,延长人类健康寿命并减少与年龄相关疾病的负担。虽然机体衰老过程是一个复杂的、多因素的过程,但有一个流行的理论认为,细胞衰老是所有多细胞生物固有进行性衰退的一个重要贡献因素。为了探索驱动细胞衰老的分子决定因素,以及如何延缓细胞衰老,研究人员利用了高度可遗传的芽殖酵母酿酒酵母(Saccharomyces cerevisiae)。事实上,在酵母中发现了已知能延长细胞和机体健康寿命的每一种干预措施,这突显了这种方法的强大。重要的是,越来越多的工作表明自噬过程在延缓衰老中起着关键作用。本综述总结了最近的研究报告,这些报告确定了自噬或自噬因子在延长酵母寿命中的作用。这些研究表明:(1) 酵母仍然是鉴定和描述促进细胞长寿的保守机制的宝贵工具,这些机制很可能与人类有关;(2) 自噬过程几乎涉及所有已知的促进长寿的操作,因此代表了改善人类健康寿命的干预措施的理想目标。