Hormonal
Inhibition of the Insulin/IGF-1 signaling (IIS) pathway extends lifespan by promoting the nuclear translocation of the DAF-16/FOXO transcription factor, which then activates downstream genes for stress resistance and longevity.
This research highlights that the body's insulin signaling system acts as a master switch for longevity. In model organisms, reducing the activity of this pathway (mimicking dietary restriction or stress) activates a specific transcription factor (FOXO/DAF-16) that moves to the cell nucleus to turn on protective genes. While this is a mechanistic finding in worms and mice, it suggests that metabolic health and insulin sensitivity are biologically linked to the aging process.
Any tense conditions that cause inner stress to block the IIS pathway like in the presence of the food restriction or the signals failed to be transduced to DAF-16/FOXO would increase the transcriptional activity of DAF-16/FOXO by inducing the translocation of DAF-16/FOXO to nucleus, which could subsequently promote or repress the expression of downstream targets to trigger the resistance to different kinds of stress and prolong the lifespan of the organisms.
Why this rating
Based on a mini-review of conserved mechanisms in C. elegans and mammals, citing multiple primary studies.
Source
DAF-16/FOXO Transcription Factor in Aging and Longevity
Xiaojuan Sun et al. · Frontiers in Pharmacology · 2017
DOI 10.3389/fphar.2017.00548
More from this paper
- Dietary restriction (caloric or nutrient restriction) extends lifespan by inactivating the TOR (Target of Rapamycin) pathway, which subsequently influences DAF-16/FOXO activity and mRNA levels.Good
- Activation of the AMP-activated protein kinase (AMPK) pathway extends lifespan and stress resistance by directly phosphorylating and activating DAF-16/FOXO.Good
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