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Published on: January 4, 2018
Insulin Signaling Functions as a Topological Switch That Couples Aging and Heat Stress Responsiveness
Manny J Widuch1, Sandra M Siepka1, Richard W Carthew1,2
1Department of Molecular Biosciences, Northwestern University, Evanston IL.
Biorxiv : the Preprint Server for Biology
|July 17, 2026
Summary
Aging and heat stress responses diverge transcriptomically in Drosophila, but Insulin/IGF-1 signaling (IIS) maintains this separation. Dampening IIS integrates these responses, improving heat shock protein production in older adults and reversing proteostasis decline.
Area of Science:
- Genetics
- Molecular Biology
- Aging Research
Background:
- Aging and thermal stress share phenotypic similarities but exhibit distinct transcriptomic patterns in Drosophila.
- The Insulin/IGF-1 signaling (IIS) pathway's role in maintaining these distinct transcriptomic signatures is unclear.
Purpose of the Study:
- To investigate the role of IIS in maintaining the distinct transcriptomic responses to aging and heat stress.
- To explore how modulating IIS affects the genomic architecture and adaptive responses to stress in aging Drosophila.
Main Methods:
- Transcriptomic analysis of Drosophila under varying IIS activity and aging conditions.
- Comparative analysis of gene expression patterns related to aging, heat stress, and IIS.
Main Results:
- High IIS activity creates separate genomic regulatory layers for aging and heat stress.
- Attenuating IIS shifts the genome to an integrated architecture, making heat stress perception age-dependent.
- Reduced IIS in old adults enhances heat shock protein induction, counteracting age-related proteostasis decline.
Conclusions:
- IIS acts as a regulatory switch, transitioning the genome between a modular growth-mode and an integrated maintenance-mode.
- The age-related dampening of heat stress response is an adaptable regulatory state, not an inevitable outcome of senescence.
- IIS pathway modulation offers a potential strategy to enhance stress resilience in aging organisms.
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