Daily rhythm disruption differed by sex and mutation in aged mice
Wheel-running experiments in aged mice with two kinds of gene disruption revealed differences in activity levels, timing and the stability of daily rhythms.
Our read
Mechanisms- Studied:
- Experiments in aged mice with ADNP disruption
- What changed:
- Daily rhythms differed by sex, with lower activity in males and shifted timing in females; another mutation showed arrhythmicity under challenge
- The catch:
- Complete loss of detectable rhythms occurred only in an exploratory cohort of males
- In the record:
- One of 6 papers on ADNP on record: none yet with results in people, 1 in animals.
Editor of record: Boris Djordjevic · AgingResearch.News
Aged mice with disruptions of the gene for activity-dependent neuroprotective protein underwent experiments measuring voluntary wheel-running. This protein helps regulate brain development and protect nerve cells. In mice with one working copy of the gene, males showed lower activity and weaker daily rhythms. Females showed shifted activity timing and more complex patterns, suggesting fragmented activity. Rhythms were less stable in both sexes.
Mice carrying a specific mutation in the same gene showed marked vulnerability only under an experimental challenge to their daily rhythms. A high proportion lacked detectable daily rhythms according to the researchers’ statistical test. In a small exploratory male group, all mice carrying this mutation lacked detectable rhythms.
Why it matters
Daily rhythm disruption is an early feature of Alzheimer’s disease and related disorders. The authors highlighted pathways involving this protein as candidate targets for future research into mechanisms and possible therapies.
Caveats
These animal experiments cannot establish whether the same changes occur in people with Alzheimer’s disease. The finding that all mutant males lacked detectable rhythms came from a small exploratory group under a rhythm challenge.
The paper
Tel Aviv University
Neurobiology of Disease, Jun 26, 2026, Open access
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