Autophagy - An Emerging Anti-Aging Mechanism?

Abstract

Autophagy is a cytoplasmic catabolic process that protects the cell against stressful conditions. Damaged cellular components are funneled by autophagy into the lysosomes, where they are degraded and can be re-used as alternative building blocks for protein synthesis and cellular repair. In contrast, aging is the gradual failure over time of cellular repair mechanisms that leads to the accumulation of molecular and cellular damage and loss of function. The cell's capacity for autophagic degradation also declines with age, and this in itself may contribute to the aging process. Studies in model organisms ranging from yeast to mice have shown that single-gene mutations can extend lifespan in an evolutionarily conserved fashion, and provide evidence that the aging process can be modulated. Interestingly, autophagy is induced in a seemingly beneficial manner by many of the same perturbations that extend lifespan, including mutations in key signaling pathways such as the insulin/IGF-1 and TOR pathways. Here, we review recent progress, primarily derived from genetic studies with model organisms, in understanding the role of autophagy in aging and age-related diseases.

Spatiotemporal regulation of autophagy during Caenorhabditis elegans aging

“…Furthermore, accumulating evidence in long-lived species demonstrates that autophagy genes are required for extended longevity. In particular, autophagy is essential for lifespan extension by inhibition of the nutrient sensor mTOR in Saccharomyces cerevisiae , C. elegans , and D. melanogaster (Gelino and Hansen, 2012; Lapierre et al, 2015). In C. elegans , autophagy genes are also required for the long lifespan induced by other conserved longevity paradigms, such as reduced insulin/IGF-1 signaling, germline ablation, and reduced mitochondrial respiration, and all these longevity mutants have increased transcript levels of several autophagy genes (Lapierre et al, 2015).…”

Effect of Wolbachia Infection on Aging and Longevity-Associated Genes in Drosophila

“…Several recent findings demonstrate that autophagy can likely contribute to many life-extending manipulations (Madeo et al 2010). In D. melanogaster, autophagy is regulated by crosstalk between IMD, JNK, TOR and IIS pathways (Gelino and Hansen 2012). One of the autophagy-related genes, autophagy-specific gene 8a (Atg8a) encodes protein that is necessary to control the intracellular Wolbachia density in many invertebrates (Voronin et al 2012).…”

Life Extension

“…Several recent findings demonstrate that autophagy can likely contribute to many life-extending manipulations ). In D. melanogaster, autophagy is regulated by crosstalk between IMD, JNK, TOR and IIS pathways (Gelino and Hansen 2012). One of the autophagy-related genes, autophagy-specific gene 8a (Atg8a) encodes protein that is necessary to control the intracellular Wolbachia density in many invertebrates (Voronin et al 2012).…”