Related Experiment Video
Updated: Jun 25, 2026
09:13
Hypoxia Alters miRNAs Levels Involved in Non-Mendelian Inheritance of Autism Spectrum Disorder in Mice
Published on: July 11, 2025
Intermittent hypoxia induces reversible epigenetic age acceleration in old mice
Stefano Donega1, Ake T Lu2, Amin Haghani3
1Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, USA, Baltimore, MD, USA.
Npj Aging
|June 23, 2026
Summary
Oxygen availability influences epigenetic aging. Intermittent hypoxia accelerated epigenetic aging in old mice, a change that reversed upon returning to normal oxygen levels, suggesting oxygen is a key driver of aging.
Area of Science:
- Epigenetics
- Aging Biology
- Physiology
Background:
- Epigenetic mechanisms regulate gene expression, but drivers of aging-associated DNA methylation are unclear.
- Previous research suggests epigenetic aging may relate to oxygen availability, particularly in immune cells near hypoxia-responsive factors.
- Hypoxia-responsive factors include Aryl hydrocarbon receptor nuclear translocator (ARNT) and RE1-silencing transcription factor (REST).
Purpose of the Study:
- To investigate the role of oxygen availability in epigenetic aging.
- To determine if intermittent hypoxia (IH) affects epigenetic age and if this effect is reversible.
Main Methods:
- Adult and old mice were exposed to IH for one month, followed by normoxic recovery.
- Epigenetic age was assessed in lungs, spleen, and heart.
- Human validation was performed using data from adults at high altitude.
Main Results:
- IH induced epigenetic age acceleration in the lungs, spleen, and heart of old mice, but not adult mice.
- This epigenetic age acceleration reversed upon return to normoxia.
- Reversible epigenetic shifts were observed at bivalent domains and Polycomb repressive complex 2 (PRC2) targets, indicating oxygen-sensitive chromatin remodeling.
- Human data confirmed rapid and conserved epigenetic aging in response to high altitude.
Conclusions:
- Oxygen availability is a primary, conserved modulator of epigenetic aging across tissues and species.
- Oxygen fluctuations are a potent and reversible driver of epigenetic aging.
- These findings highlight the dynamic interplay between oxygen homeostasis and the aging epigenome.
