Journal
AGING CELL
Volume 11, Issue 3, Pages 491-499Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1474-9726.2012.00811.x
Keywords
aging; DAF-16; development; heat shock factor 1; insulin; IGF-1 signaling
Categories
Funding
- United States - Israel Binational Science Foundation [BSF 2009465]
- Marie Curie Reintegration grant [IRG 279134]
- Howard Hughes Medical Institute
- NIA [P01 AG031097]
Ask authors/readers for more resources
Reducing the activity of the insulin/IGF-1 signaling pathway (IIS) modifies development, elevates stress resistance, protects from toxic protein aggregation (proteotoxicity), and extends lifespan (LS) of worms, flies, and mice. In the nematode Caenorhabditis elegans, LS extension by IIS reduction is entirely dependent upon the activity of the transcription factors DAF-16 and the heat shock factor-1 (HSF-1). While DAF-16 determines LS exclusively during early adulthood, it is required for proteotoxicity protection also during late adulthood. In contrast, HSF-1 protects from proteotoxicity during larval development. Despite the critical requirement for HSF-1 for LS extension, the temporal requirements for this transcription factor as a LS determinant are unknown. To establish the temporal requirements of HSF-1 for longevity assurance, we conditionally knocked down hsf-1 during larval development and adulthood of C. elegans and found that unlike daf-16, hsf-1 is foremost required for LS determination during early larval development, required for a lesser extent during early adulthood and has small effect on longevity also during late adulthood. Our findings indicate that early developmental events affect LS and suggest that HSF-1 sets during development of the conditions that enable DAF-16 to promote longevity during reproductive adulthood. This study proposes a novel link between HSF-1 and the longevity functions of the IIS.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available