NeuronAug 7, 2026

Changes in cell metabolism over time influence support cell development in aging and multiple sclerosis

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 8, 2026

Abstract

Dysregulation of Bmal1 and metabolic genes in aged oligodendrocyte precursor cells (OPCs) is associated with impaired myelin renewal.

Impaired OPC differentiation contributes to myelin renewal limitations in aging and multiple sclerosis (MS).
Targeted loss of Bmal1 in OPCs leads to metabolic dysfunction and cellular aging.
Proliferation and differentiation of OPCs vary throughout the day in young adult mice but are disrupted with aging.
Restoring BMAL1-controlled signaling can improve OPC dynamics after demyelination through mechanisms involving sirtuin 2 (Sirt2).
Induced pluripotent stem cell-derived OPCs from MS patients show similar disruptions in BMAL1 and SIRT2 as observed in aged cells.

Simplified

Impaired oligodendrocyte precursor cell (OPC) differentiation limits myelin renewal in aging and contributes to multiple sclerosis (MS) progression. How aging drives OPC deficits remains incompletely understood. We find dysregulation of genes associated with the circadian clock, including Bmal1, and metabolism in aged compared with young OPCs. Targeted loss of Bmal1 in OPCs drives metabolic dysfunction, leading to cellular senescence and impaired dynamics. OPC proliferation and differentiation occur at different rates throughout the day in young adult mice and become disrupted with aging. Chronotherapeutic targeting of BMAL1-controlled sirtuin signaling restores Bmal1-disrupted OPC dynamics after demyelination via sirtuin 2 (Sirt2)-dependent mechanisms. Induced pluripotent stem cell (iPSC)-derived OPCs from MS patients and MS lesion oligodendroglia recapitulate BMAL1 and SIRT2 disruptions. These findings establish BMAL1 as a key regulator of OPC energy metabolism, sirtuin homeostasis, and senescence. We anticipate that this work will provide a foundation for future studies investigating the interconnected roles of aging, circadian disruption, and myelin biology.