Evidence map›Paper›PMID 42337297›Full record

Articlenpj aging2026

Intermittent hypoxia induces reversible epigenetic age acceleration in old mice.

Stefano Donega, Ake T Lu, Amin Haghani, Markus Horvath, Qi Yan, Mirko Baranzini, Maxine Thea Escote, Martina Rossi, Rolando J Hernandez, Ross A McDevitt and 3 more

Abstract read
PubMed Publisher
In one paragraph

Article in npj aging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Stefano Donega *Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, USA, Baltimore, MD, USA.
Ake T Lu *Epigenetic Clock Development Foundation, Torrance, CA, USA.
Amin HaghaniAltos Labs, San Diego Institute, California, CA, USA.
Markus HorvathEpigenetic Clock Development Foundation, Torrance, CA, USA.
Qi YanAltos Labs, San Diego Institute, California, CA, USA.
Mirko BaranziniLongitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, USA, Baltimore, MD, USA.
Maxine Thea EscoteComparative Medicine Section, National Institute on Aging, National Institutes of Health, USA, Baltimore, MD, USA.
Martina RossiLongitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, USA, Baltimore, MD, USA.
Rolando J HernandezComparative Medicine Section, National Institute on Aging, National Institutes of Health, USA, Baltimore, MD, USA.
Ross A McDevittComparative Medicine Section, National Institute on Aging, National Institutes of Health, USA, Baltimore, MD, USA.
Kenneth W FishbeinMRI Core Facility for Translational Research, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Steve HorvathEpigenetic Clock Development Foundation, Torrance, CA, USA. shorvath@mednet.ucla.edu.
Luigi FerrucciLongitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, USA, Baltimore, MD, USA. ferruccilu@grc.nia.nih.gov.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epigenetic mechanisms are considered adaptive regulators of gene expression, yet mechanisms driving aging-associated DNA methylation remain unclear. Prior work hinted that epigenetic aging might reflect a response to oxygen availability, with age‑differential methylation in immune cells enriched near binding sites for hypoxia‑responsive factors ARNT and REST. To test this hypothesis, we exposed adult (11 months) and old (23 months) mice to 1 month of intermittent hypoxia (IH) followed by normoxic recovery. IH induced epigenetic age acceleration in lungs, spleen, and heart in old mice only. This acceleration reversed upon return to normoxia. Reversible shifts were enriched at bivalent domains and PRC2 targets, indicating oxygen-sensitive chromatin remodeling. Human translational validation in young adults at high altitude (5260 m) confirmed rapid, conserved epigenetic aging. Our findings establish oxygen availability as a primary, conserved modulator of epigenetic aging across tissues and species, showing that oxygen fluctuations are a potent, reversible driver of epigenetic aging.

Identifiers

PMID42337297

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.