The conserved target of rapamycin (TOR) pathway integrates signals from nutrient and energy availability, growth factors and stress to regulate cell growth and proliferation, development and metabolism. Growing evidence suggests that TOR signalling controls the rate at which cells and tissues age, thereby contributing to whole-organism ageing. Although significant progress has been made in the last decades towards understanding fundamental aspects of the ageing process, the precise mechanisms underlying the age-related effects of TOR are still not fully understood. TOR interfaces with several cellular processes, such as DNA transcription, mRNA translation, protein turnover and autophagy, among others. Interestingly, TOR regulates various aspects of metabolism including mitochondrial function and lipid metabolism. Inhibition of TOR activity stimulates autophagy, a conserved lysosomal catabolic pathway that controls the degradation and turnover of macromolecules and organelles. Autophagy also has an important role in maintaining metabolic homeostasis at both the cellular and whole-organism level. Ageing in diverse organisms ranging from yeast to mammals appears to be associated with insufficient autophagy. Here, we summarize recent developments that outline how TOR and autophagy modulate the ageing process, with special emphasis on their role in the regulation of metabolism. A better understanding of the complex interplay between TOR, autophagy and ageing will pave the way for the development of novel therapeutic strategies to treat age-related pathologies.

• PMID: 23594965
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Journal Article | Research Support, Non-U.S. Gov't | Review

Authors

Markaki M, Tavernarakis N

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