Aging activates latent enhancers that can be reversed withexercise

Aging in the mouse heart increases AP-1 engagement at more than 100,000 regulatory loci across cardiac cell types, and endurance exercise opposes most of these gains.

• Why it matters: Age-related remodeling of gene regulation is known to occur, but which enhancer elements become active with age and whether exercise can attenuate them in aged animals is unclear.
• What they did: Using single-cell multiomics in mouse heart, the study mapped age-responsive cis-regulatory elements and tested endurance exercise effects with reporter assays and enhancer perturbations, including IL-1 neutralization and AP-1 inhibition in vivo.
• The result: Age-gained enhancer sequences showed reporter activity comparable to stable elements despite low endogenous accessibility, and IL-1-sensitive enhancers were preferentially responsive to cytokine neutralization; AP-1 inhibition further opposed age-associated transcription.

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