Frontiers in neuroendocrinologyOct 26, 2026

How Changes in Daily Hormone Cycles Relate to Brain Aging, Disease, and Personalized Timing Treatments

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 27, 2026

Abstract

Circadian aging may promote neurodegenerative illnesses by dysregulating the melatonin-cortisol axis.

Low nighttime melatonin synthesis and blunted cortisol circadian cycles are associated with age-related neurodegenerative diseases.
Abnormal patterns in clock genes and sleep-wake architecture may compromise circadian balance, leading to neuroinflammation and oxidative stress.
Altered neuroendocrine function is linked to mitochondrial failure and loss of immune function in the central nervous system.
Impaired glymphatic clearance and blood-brain barrier dysregulation could contribute to the progression of various dementias.
New biomarkers and treatment strategies focusing on the melatonin-cortisol axis may help in identifying and managing age-related neurodegenerative diseases.

Simplified

Circadian aging may promote neurodegenerative illnesses by dysregulating the melatonin-cortisol axis. Low nighttime melatonin synthesis, blunted cortisol circadian cycles, abnormal clock-gene oscillation patterns, and sleep-wake architecture undermine central and peripheral circadian equilibrium with age. Neuroendocrine alterations produce oxidative stress, mitochondrial failure, pervasive neuroinflammation (CNS immune function loss), and proteostasis. Increasing Alzheimer's, Parkinson's, ALS, Huntington's, frontotemporal dementia, Lewy body disease, PTSD, and vascular cognitive impairment due to impaired glymphatic axonal clearance/blood-brain barrier dysregulation/synaptic degeneration/pathoproteopathic protein We examine how clock genes, melatonin signaling, hypothalamic-pituitary-adrenal axis administration, microglia reactivity, and immune-mediated metabolic dysregulation affect dementia. New endocrine, transcriptomic, multi-omics, and wearable-derived digital biomarkers, chronopharmacology (including melatonin receptor agonists), bright-light therapy, time-restricted eating with exercise chronotherapy guidance/synchronization, sleep optimization, and gut microbiota modulation This study addressed inter-individual circadian variability, genetic susceptibility to therapy timing, biomarker standardization, and clinical trial design. The melatonin-cortisol axis may identify and treat age-related neurodegenerative diseases with tailored treatment.

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How Changes in Daily Hormone Cycles Relate to Brain Aging, Disease, and Personalized Timing Treatments

Abstract

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