“ With age, mitochondrial health and function become altered in muscle, but the role of ATF5 in regulating these processes has not yet been evaluated . ”
BUFFALO, NY — April 9, 2026 — A new research paper was published in Volume 18 of Aging-US on March 27, 2026, titled “ ATF5 is required for the maintenance of mitochondrial homeostasis and skeletal muscle health during aging .”
Led by first author Victoria C. Sanfrancesco and corresponding author David A. Hood, both from the Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada , the study investigated the role of activating transcription factor 5 (ATF5) in regulating mitochondrial quality control and skeletal muscle function during aging.
Using young and aged mouse models with and without ATF5 expression, the researchers examined how this transcription factor contributes to mitochondrial homeostasis, protein turnover, and stress response pathways. The analysis focused on key mechanisms such as the integrated stress response (ISR) and mitochondrial unfolded protein response (UPRmt), which are essential for maintaining mitochondrial integrity.
The authors found that ATF5 plays a critical role in coordinating mitochondrial quality control and adaptive stress signaling in skeletal muscle. Notably, the absence of ATF5 prevented the typical age-related decline in muscle mass but resulted in increased muscle fatigability and elevated mitochondrial reactive oxygen species (ROS) production. Additionally, the loss of ATF5 disrupted normal stress-response signaling and altered protein degradation pathways, highlighting its importance in maintaining muscle function with age.
“ Collectively, these results suggest that ATF5 functions to maintain mitochondrial quality control and muscle endurance at the expense of muscle mass, and its absence attenuates the normal compensatory stress response to contractile activity with age . ”
The authors conclude that while ATF5 contributes to preserving mitochondrial function and endurance capacity, its role in regulating muscle mass and stress adaptation is complex. Further studies are needed to clarify how modulation of ATF5 and related pathways could be leveraged to improve muscle health and mitigate age-related decline in mitochondrial function and physical performance.
Paper DOI : https://doi.org/10.18632/aging.206365
Corresponding author: David A. Hood – dhood@yorku.ca
Keywords: skeletal muscle, ATF5, mitochondria, aging, stress response
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ATF5 is required for the maintenance of mitochondrial homeostasis and skeletal muscle health during aging
27-Mar-2026
The authors declare that they have no conflicts of interest.