Transcriptional regulation of autophagy in aging

Abstract

Macroautophagy, hereafter autophagy, is a cellular recycling process that degrades damaged cellular components. Autophagy is important for maintaining cellular homeostasis and has been reported to decline with age. This age-related reduction in autophagy function has been associated with the development of age-related diseases. A network of signaling pathways that sense nutrient status and cellular stress regulate autophagy via post-translational, transcriptional, and epigenetic mechanisms, but the molecular mechanisms that lead to autophagy decline with age remain unclear. Here, we review links between autophagy and aging and focus on the hypothesis that transcriptional dysregulation of key autophagy genes contributes to the age-related decline in autophagy. We outline how transcription factors TFEB (transcription factor EB) and FOXOs ( forkhead box-O family proteins) facilitate appropriate transcriptional regulation of autophagy in healthy organisms, and summarize recent advances characterizing age-related changes in the regulation of transcription-factor function that could contribute to transcriptional dysregulation of autophagy.