The interplay between circadian rhythms and aging: molecular mechanisms and therapeutic strategies.

Biogerontology 2025
Open on PubMed

Circadian rhythms are essential biological systems operating on a 24-h cycle, playing a crucial role in regulating sleep, cognitive function, immune responses, and hormone secretion. This review explores the intricate relationship between circadian rhythms and aging, with a focus on the underlying molecular mechanisms. It discusses age-related changes in sleep patterns and the role of circadian disruption in the progression of neurodegenerative diseases such as Parkinson's and Alzheimer's. Special attention is given to the core CLOCK genes, including BMAL1 and Per2, and their regulatory influence on these processes. The review also highlights the impact of circadian misalignment on metabolic disorders, particularly obesity, diabetes, and cardiovascular disease. Emerging therapeutic strategies targeting circadian pathways-ranging from pharmacological agents to lifestyle modifications-are presented as promising approaches to support healthy aging. This review provides the deeper understanding of how aging affects circadian regulation may pave the way for targeted interventions aimed at extending lifespan and enhancing overall quality of life.

7 Figures Extracted
Fig. 1.
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Effects of CR on body weight, circadian behavior and feeding in C57BL/6J male mice. (A) Experimental design showing feeding conditions for each of th...
Fig. 2.
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Extent of CR-mediated increases in longevity depend on feeding time. (A) Survival curves for each group (n = 43 for AL and n = 36 for each of the CR)...
Fig. 3.
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Gene expression signatures in liver change during aging in AL mice. (A) Principal component analysis of gene expression from liver mRNA-seq. mRNA-seq...
Fig. 4.
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CR ameliorates age-related changes in liver gene expression observed under AL. (A) Schematic comparison of differential gene expression between young...
Fig. 5.
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Circadian rhythms in liver gene expression are blunted during aging in AL mice. (A) Gene expression patterns from mRNA-seq were analyzed for circadia...
Fig. 6.
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Effects of caloric restriction and phase of feeding on circadian gene expression. (A) Gene expression patterns from mRNA-seq were analyzed for circad...
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