Open Accessm TORC 2‐ SGK ‐1 acts in two environmentally responsive pathways with opposing effects on longevity
Author(s) -
Mizunuma Masaki,
NeumannHaefelin Elke,
Moroz Natalie,
Li Yujie,
Blackwell T. Keith
Publication year - 2014
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12248
Subject(s) - mtorc2 , mtorc1 , biology , pi3k/akt/mtor pathway , microbiology and biotechnology , longevity , context (archaeology) , signal transduction , genetics , paleontology
Summary The nematode worm Caenorhabditis elegans provides a powerful system for elucidating how genetic, metabolic, nutritional, and environmental factors influence aging. The mechanistic target of rapamycin (m TOR ) kinase is important in growth, disease, and aging and is present in the m TORC 1 and m TORC 2 complexes. In diverse eukaryotes, lifespan can be increased by inhibition of m TORC 1, which transduces anabolic signals to stimulate protein synthesis and inhibit autophagy. Less is understood about m TORC 2, which affects C. elegans lifespan in a complex manner that is influenced by the bacterial food source. m TORC 2 regulates C. elegans growth, reproduction, and lipid metabolism by activating the SGK ‐1 kinase, but current data on SGK ‐1 and lifespan seem to be conflicting. Here, by analyzing the m TORC 2 component Rictor ( RICT ‐1), we show that m TORC 2 modulates longevity by activating SGK ‐1 in two pathways that affect lifespan oppositely. RICT ‐1/m TORC 2 limits longevity by directing SGK ‐1 to inhibit the stress‐response transcription factor SKN ‐1/Nrf in the intestine. Signals produced by the bacterial food source determine how this pathway affects SKN ‐1 and lifespan. In addition, RICT ‐1/m TORC 2 functions in neurons in an SGK ‐1‐mediated pathway that increases lifespan at lower temperatures. RICT ‐1/m TORC 2 and SGK ‐1 therefore oppose or accelerate aging depending upon the context in which they are active. Our findings reconcile data on SGK ‐1 and aging, show that the bacterial microenvironment influences SKN ‐1/Nrf, m TORC 2 functions, and aging, and identify two longevity‐related m TORC 2 functions that involve SGK ‐regulated responses to environmental cues.