Restoring circadian rhythms in the hypothalamic paraventricular nucleus reverses aging biomarkers and extends lifespan in male mice - PubMed
2 hours ago
- #aging
- #lifespan extension
- #circadian rhythms
- Restoring circadian rhythms in the hypothalamic paraventricular nucleus (PVN) reverses aging biomarkers and extends lifespan in male mice.
- 3'-deoxyadenosine (3dA) strengthens circadian amplitude in PVN neurons, mitigates aging biomarkers, and extends lifespan.
- 3dA restores clock synchrony, hormonal rhythms (e.g., corticosterone), and reduces epigenetic age measured by DNA methylation clocks.
- Transcriptomic, hormonal, and epigenetic profiling show increased PVN circadian amplitude after timed 3dA administration.
- PVN-specific knockout of Ruvbl2 abolishes 3dA's benefits, establishing its genetic necessity.
- Chemogenetic PVN activation replicates 3dA's metabolic and physiological benefits.
- The PVN clock is identified as a pharmacological node linking circadian amplitude to organismal aging.
- Targeting RUVBL2-dependent circadian transcription enhances network synchrony.
- Circadian interventions are promising therapeutic candidates for delaying aging and improving healthspan in aged male mice.