Interesting work. But the actual costs on lifespan are minimal right? So the costs on lifespan cannot pose a constraint on reproductive effort even in a harsh environment? Half a year is tiny. Immediate mortality costs would have a stronger fitness effect.

CIRBP expression in the fly extends lifespan and improves resistance to lethal radiation. For myself it sparked a renewed interest in DNA repair and somatic mutations. We are trying a few things in this space at the moment in the lab.

and aging remain elusive, why longer-lived organisms show more signs of aging during their natural lifespans, and why longer-lived organisms can be less responsive to treatments of aging that work well in short-lived organisms. We provide predictions of our theory that are empirically testable.

Our model explains many puzzling aspects of aging. These include why aging appears (but is not) programmed, why aging is gradual yet heterogeneous, why cellular and hormonal signaling are closely related to aging, the compensation law of mortality, why trade-offs between reproduction...

Optimisation models of physiology often use immunity as an example, with the cost of underactivating immunity being steepest, as this would lead to death by infection. Our model predicts that the system will on average drift to overactivation of immunity during aging.

The regulation of such physiology will be asymmetrical as the costs of loss of regulation are not equal for under- and over-activation. When asymmetrical regulation breaks during aging it causes physiological function to drift towards the physiological range where costs of dysregulation are lowest.

A synopsis:
Life has evolved to secure reproduction and avoid system failure in early life and it is the physiological regulation that evolves in response to those early life selection pressures that leads to the emergence of aging.

The biology of aging is something fundamental to all life, but we have a limited understanding of its physiology and its evolution. I presented this idea at #ARDD2025 and at the #BRSA2025 and many of you asked if there was a preprint, now there is. I welcome any feedback!

@miriamgotz.bsky.social

The majority of this work was done by my student Miriam, she has done an amazing job. Similarly interested in studying in one of the best biology departments in the UK?: sheffield.ac.uk/biosciences

Our study in the fly shows that suppression rather than activation extends lifespan in the fly. Opening up a lot of interesting questions, including how we can target ATF4 or its downstream targets to gain longevity benefits.

Mild stress is associated with longer lifespans. Activation of the integrated stress response, governed by the transcription factor ATF4 is therefore thought to lead to longer lifespans, but has received limited study.

It’s because we are top100 now, hahahaha