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Cell Rep. 2013 Dec 26;5(6):1600-10. doi: 10.1016/j.celrep.2013.11.018. Epub 2013 Dec 12.

Germline signaling mediates the synergistically prolonged longevity produced by double mutations in daf-2 and rsks-1 in C. elegans.

Author information

1
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, 12 Xuefu Road, Pukou District, Nanjing, Jiangsu 210061, China. Electronic address: chendi@nju.edu.cn.
2
Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
3
School of Public Health, University of California, Berkeley, Berkeley, CA 94720, USA.
4
Institute of Traditional Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China.
5
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, 12 Xuefu Road, Pukou District, Nanjing, Jiangsu 210061, China.
6
Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA. Electronic address: pkapahi@buckinstitute.org.

Abstract

Inhibition of DAF-2 (insulin-like growth factor 1 [IGF-1] receptor) or RSKS-1 (S6K), key molecules in the insulin/IGF-1 signaling (IIS) and target of rapamycin (TOR) pathways, respectively, extend lifespan in Caenorhabditis elegans. However, it has not been clear how and in which tissues they interact with each other to modulate longevity. Here, we demonstrate that a combination of mutations in daf-2 and rsks-1 produces a nearly 5-fold increase in longevity that is much greater than the sum of single mutations. This synergistic lifespan extension requires positive feedback regulation of DAF-16 (FOXO) via the AMP-activated protein kinase (AMPK) complex. Furthermore, we identify germline as the key tissue for this synergistic longevity. Moreover, germline-specific inhibition of rsks-1 activates DAF-16 in the intestine. Together, our findings highlight the importance of the germline in the significantly increased longevity produced by daf-2 rsks-1, which has important implications for interactions between the two major conserved longevity pathways in more complex organisms.

PMID:
24332851
PMCID:
PMC3904953
DOI:
10.1016/j.celrep.2013.11.018
[Indexed for MEDLINE]
Free PMC Article
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