Format

Send to

Choose Destination
Aging Cell. 2017 Dec;16(6):1219-1233. doi: 10.1111/acel.12689. Epub 2017 Oct 2.

TOR-mediated regulation of metabolism in aging.

Author information

1
Federated Department of Biological Sciences, New Jersey Institute of Technology, Rutgers University, Newark, NJ, 07102, USA.
2
Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ, 08854, USA.

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.

KEYWORDS:

mTOR ; aging; autophagy; lysosomal clearance; metabolism

PMID:
28971552
PMCID:
PMC5676073
DOI:
10.1111/acel.12689
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center