Diet restriction‐induced healthy aging is mediated through the immune signaling component ZIP‐2 in Caenorhabditis elegans. Issue 5 (18th June 2019)

• Record Type: Journal Article
• Authors: Hahm, Jeong‐Hoon; Jeong, ChoLong; Nam, Hong Gil
• Is Part Of: Aging cell. Volume 18:Issue 5(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-06-18
• Subjects: C. elegans -- dietary restriction -- longevity -- mitochondria -- TOR/S6K -- ZIP‐2; Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.12982
• Languages: English
• ISSNs: 1474-9718

Abstract

Abstract: Dietary restriction (DR) robustly delays the aging process in all animals tested so far. DR slows aging by negatively regulating the target of rapamycin (TOR) and S6 kinase (S6K) signaling pathway and thus inhibiting translation. Translation inhibition in C. elegans is known to activate the innate immune signal ZIP‐2. Here, we show that ZIP‐2 is activated in response to DR and in feeding‐defective eat‐2 mutants. Importantly, ZIP‐2 contributes to the improvements in longevity and healthy aging, including mitochondrial integrity and physical ability, mediated by DR in C. elegans . We further show that ZIP‐2 is activated upon inhibition of TOR/S6K signaling. However, DR‐mediated activation of ZIP‐2 does not require the TOR/S6K effector PHA‐4/FOXA. Furthermore, zip‐2 was not activated or required for longevity in daf‐2 mutants, which mimic a low nutrition status. Thus, DR appears to activate ZIP‐2 independently of PHA‐4/FOXA and DAF‐2. The link between DR, aging, and immune activation provides practical insight into the DR‐induced benefits on health span and longevity. Abstract : Dietary restriction (DR) activates an innate immune signal, ZIP‐2, through inhibition of TOR/S6K signaling in Caenorhabditis elegans . ZIP‐2 mediates the benefitial DR effects on longevity and health parameters such as improved mitochondrial integrity and physical ability.