Neuroendocrine timekeepers: changes in normal and premature aging

The hypothalamus is a central regulator of circadian rhythms, metabolism, and endocrine function, integrating internal and external cues to maintain physiological homeostasis. Aging impairs hypothalamic function, leading to metabolic changes, sleep disturbances, and a higher risk of age-related disease. Laminopathies - rare genetic disorders marked by premature aging - exhibit profound neuroendocrine and circadian rhythm dysfunction, offering insights into mechanisms of hypothalamic aging. The complex interplay between the hypothalamus, circadian rhythms, and systemic aging highlights the critical role of neuroendocrine crosstalk in the regulation of health span and life span. This review summarizes emerging molecular and physiological insights into hypothalamic aging and circadian misalignment, and highlights potential interventions, such as chronotherapy and caloric restriction, that may alleviate hypothalamic alterations and promote healthy aging.