Integrin‐linked kinase modulates longevity and thermotolerance in C. elegans through neuronal control of HSF‐1

Aging Cell

Caroline Kumsta²  Tsui-Ting Ching¹  Mayuko Nishimura²  Andrew E. Davis²  Sara Gelino²  Hannah H. Catan²  Xiaokun Yu¹  Chu-Chiao Chu²  Binnan Ong²  Siler H. Panowski³  Nathan Baird³  Rolf Bodmer²  Ao-Lin Hsu¹ 

[1] Department of Internal Medicine, Division of Geriatric and Palliative Medicine, University of Michigan Medical School, Ann Arbor, MI, USA;Development, Aging and Regeneration Program, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA;The Glenn Center for Aging Research, The Salk Institute for Biological Studies, The Howard Hughes Medical Institute, La Jolla, CA, USA

关键词: aging;    C. elegans;    heat‐shock response;    HSF‐1;    integrin signaling;    PAT‐4/ILK;   

DOI  :  10.1111/acel.12189

来源: Wiley

【 摘 要 】

Summary

Integrin-signaling complexes play important roles in cytoskeletal organization and cell adhesion in many species. Components of the integrin-signaling complex have been linked to aging in both Caenorhabditis elegans and Drosophila melanogaster, but the mechanism underlying this function is unknown. Here, we investigated the role of integrin-linked kinase (ILK), a key component of the integrin-signaling complex, in lifespan determination. We report that genetic reduction of ILK in both C. elegans and Drosophila increased resistance to heat stress, and led to lifespan extension in C. elegans without majorly affecting cytoskeletal integrity. In C. elegans, longevity and thermotolerance induced by ILK depletion was mediated by heat-shock factor-1 (HSF-1), a major transcriptional regulator of the heat-shock response (HSR). Reduction in ILK levels increased hsf-1 transcription and activation, and led to enhanced expression of a subset of genes with roles in the HSR. Moreover, induction of HSR-related genes, longevity and thermotolerance caused by ILK reduction required the thermosensory neurons AFD and interneurons AIY, which are known to play a critical role in the canonical HSR. Notably, ILK was expressed in neighboring neurons, but not in AFD or AIY, implying that ILK reduction initiates cell nonautonomous signaling through thermosensory neurons to elicit a noncanonical HSR. Our results thus identify HSF-1 as a novel effector of the organismal response to reduced ILK levels and show that ILK inhibition regulates HSF-1 in a cell nonautonomous fashion to enhance stress resistance and lifespan in C. elegans.

【 授权许可】

CC BY   
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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