Multifaceted dynamics of circadian timing system influence aging and longevity

📖 Top 20% JournalSep 27, 2025Biogerontology

How different parts of the body’s internal clock affect aging and lifespan

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Desynchrony between central and peripheral clocks may contribute to age-related conditions such as metabolic syndrome and cognitive decline.

Circadian time keeping system regulates physiological, metabolic, and behavioral processes in a 24-hour cycle.
Aging affects circadian rhythms and can lead to systemic decline, impacting both central and peripheral clocks.
Sex-specific factors and hormonal changes may influence circadian resilience and contribute to age-related vulnerabilities.
Diminished transcriptional rhythmicity and disruptions in neurotransmitter systems are observed with aging.
The breakdown of circadian harmony is associated with accelerated aging and increased susceptibility to circadian rhythm disorders.

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Circadian time keeping system (CTS) consisting of network of central and peripheral clocks regulates physiological, metabolic, and behavioural processes in alignment with the 24 hour. Desynchrony between central and peripheral clocks contributes to the pathogenesis of age-related conditions such as metabolic syndrome, cognitive decline, immune dysfunction, and neurodegenerative diseases etc. Sex-specific susceptibilities further modulate circadian resilience, with hormonal changes and redox imbalances playing key roles in the aging trajectory. Immune senescence and hormonal dampening, particularly in cortisol and melatonin rhythms, exacerbate circadian misalignment, accelerating systemic decline with aging. Interestingly, aging and clock dysfunction is a bidirectional process, i.e. aging progressively influences circadian rhythms across multiple levels and vice versa, from the molecular architecture of core clock gene feedback loops to the functionality of the central pacemaker-the suprachiasmatic nucleus (SCN)-and its coordination with peripheral oscillators. This review critically highlights the complex alterations in circadian mechanisms associated with aging, including diminished transcriptional rhythmicity, epigenetic drift, mitochondrial desynchronization, and disruptions in neurotransmitter systems. Such changes in turn leads to weakened SCN output, impaired photic entrainment, and loss of temporal coherence across organ systems. Further, this review demonstrates CTS and aging at multiple levels such as behavioural, physiological, biochemical and molecular levels are linked in push-pull mechanism i.e., the breakdown in the harmony of circadian rhythms at systemic level pushes the organism towards early aging and aging in turn is linked to CTS disorders.

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