TOR-mediated regulation of metabolism in aging

Document Type

Article

Publication Date

12-1-2017

Abstract

Cellular metabolism is regulated by the mTOR kinase, a key component of the molecular nutrient sensor pathway that plays a central role in cellular survival and aging. The mTOR pathway promotes protein and lipid synthesis and inhibits autophagy, a process known for its contribution to longevity in several model organisms. The nutrient-sensing pathway is regulated at the lysosomal membrane by a number of proteins for which deficiency triggers widespread aging phenotypes in tested animal models. In response to environmental cues, this recently discovered lysosomal nutrient-sensing complex regulates autophagy transcriptionally through conserved factors, such as the transcription factors TFEB and FOXO, associated with lifespan extension. This key metabolic pathway strongly depends on nucleocytoplasmic compartmentalization, a cellular phenomenon gradually lost during aging. In this review, we discuss the current progress in understanding the contribution of mTOR-regulating factors to autophagy and longevity. Furthermore, we review research on the regulation of metabolism conducted in multiple aging models, including Caenorhabditis elegans, Drosophila and mouse, and human iPSCs. We suggest that conserved molecular pathways have the strongest potential for the development of new avenues for treatment of age-related diseases.

Identifier

85033223729 (Scopus)

Publication Title

Aging Cell

External Full Text Location

https://doi.org/10.1111/acel.12689

e-ISSN

14749726

ISSN

14749718

PubMed ID

28971552

First Page

1219

Last Page

1233

Issue

6

Volume

16

Grant

13447

Fund Ref

American Federation for Aging Research

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