A new study from the University of Sheffield, conducted on tens of thousands of fruit flies, suggests that suppressing the body’s internal stress response may extend lifespan challenging earlier research that proposed mild stress could promote longevity. Published in the Proceedings of the National Academy of Sciences (PNAS), the findings highlight the role of the Integrated Stress Response (ISR), a cellular “emergency management” system that helps cells cope with challenges such as nutrient deprivation and viral infections. The study points toward the possibility of targeting fundamental aging processes rather than individual diseases, offering a potentially scalable approach to addressing the growing global burden of aging populations.

In the first test of whether mild activation of stress through the Integrated Stress Response (ISR) could extend lifespan in a complex organism, researchers  found the opposite effect: suppressing the stress response prolonged life in fruit flies. Studying tens of thousands of flies, the team showed that artificially increasing ISR activity effectively mimicking a state of stress reduced lifespan, whereas dampening this pathway enabled the flies to live longer, even under conditions such as dietary stress. These results contrast with earlier findings in simpler organisms like yeast and Caenorhabditis elegans, where activating stress responses appeared to promote longevity, as well as prior evidence from mouse studies suggesting a beneficial role of ISR activation.

Dr. Mirre Simons of the University of Sheffield School of Biosciences emphasized that targeting the aging process itself could significantly extend human lifespan and help address the growing societal and economic pressures associated with an aging population. Rather than focusing solely on individual diseases, she highlighted the need for scalable interventions that act on fundamental aging mechanisms. The research team selected fruit flies due to their relatively complex biology and short two-month lifespan, making them well suited for longevity studies. Their findings showed that suppressing the Integrated Stress Response (ISR) consistently extended lifespan, regardless of factors such as dietary changes. The study also suggests that a deeper understanding of the ISR pathway may have broader implications for advancing other areas of medicine.

Miriam Götz, a graduate of the University of Sheffield and co-author of the study, noted that the Integrated Stress Response (ISR) pathway is already a key area of focus in fields such as cancer and immunology, and that these findings enhance the broader understanding of biological mechanisms with potential to improve treatments for age related conditions. Building on this work, the Sheffield research team is now seeking funding to investigate whether existing drugs can reproduce the lifespan extending effects observed through genetic modification, which could pave the way for pharmacological approaches to slowing the aging process.

source: https://sheffield.ac.uk/news/silencing-stress-signals-could-pave-way-longer-life-study-reveals