Lapierre Louis R, Kumsta Caroline, Sandri Marco, Ballabio Andrea, Hansen Malene
a Development, Aging and Regeneration Program; Sanford-Burnham Medical Research Institute ; La Jolla , CA USA.
Autophagy. 2015;11(6):867-80. doi: 10.1080/15548627.2015.1034410.
Macroautophagy is a major intracellular degradation process recognized as playing a central role in cell survival and longevity. This multistep process is extensively regulated at several levels, including post-translationally through the action of conserved longevity factors such as the nutrient sensor TOR. More recently, transcriptional regulation of autophagy genes has emerged as an important mechanism for ensuring the somatic maintenance and homeostasis necessary for a long life span. Autophagy is increased in many long-lived model organisms and contributes significantly to their longevity. In turn, conserved transcription factors, particularly the helix-loop-helix transcription factor TFEB and the forkhead transcription factor FOXO, control the expression of many autophagy-related genes and are important for life-span extension. In this review, we discuss recent progress in understanding the contribution of these transcription factors to macroautophagy regulation in the context of aging. We also review current research on epigenetic changes, such as histone modification by the deacetylase SIRT1, that influence autophagy-related gene expression and additionally affect aging. Understanding the molecular regulation of macroautophagy in relation to aging may offer new avenues for the treatment of age-related diseases.
巨自噬是一种主要的细胞内降解过程，被认为在细胞存活和寿命方面发挥着核心作用。这个多步骤过程在多个层面受到广泛调控，包括翻译后通过营养传感器TOR等保守的长寿因子的作用进行调控。最近，自噬基因的转录调控已成为确保长寿所需的体细胞维持和体内平衡的重要机制。在许多长寿模式生物中，自噬增加，并且对它们的长寿有显著贡献。反过来，保守的转录因子，特别是螺旋-环-螺旋转录因子TFEB和叉头转录因子FOXO，控制许多自噬相关基因的表达，对寿命延长很重要。在这篇综述中，我们讨论了在衰老背景下理解这些转录因子对巨自噬调控作用方面的最新进展。我们还综述了当前关于表观遗传变化的研究，如去乙酰化酶SIRT1对组蛋白的修饰，其影响自噬相关基因表达并进而影响衰老。了解与衰老相关的巨自噬的分子调控可能为治疗与年龄相关的疾病提供新途径。
