NeuronSep 18, 2026

A molecular pathway linking body signals to thinking problems in women during midlife

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 19, 2026

Abstract

Senescence-associated features were preferentially elevated in middle-aged females in human brain and spleen tissues.

Female mice showed an epigenetic increase in the X-linked RNA-binding protein RBMX, which may contribute to midlife changes.
Increased levels of miR-10a-5p in the spleen were associated with the upregulation of RBMX.
miR-10a-5p was found to repress a specific enzyme linked to calcium signaling, which could affect mitochondrial health and cellular aging.
Inhibition of miR-10a-5p in neurons from Alzheimer's patients and model mice reduced disease-related characteristics.
These findings suggest a connection between peripheral and brain factors that may influence cognitive decline during female midlife.

Simplified

Although women live longer, they paradoxically face heightened susceptibility to cognitive and systemic decline emerging in midlife-an underexplored transition from resilience to vulnerability. Here, we investigate biological processes associated with this female-biased vulnerability and their molecular regulation. Senescence-associated features were preferentially elevated in middle-aged females in human brain and spleen tissues, with similar changes in mice. In female mice, epigenetic upregulation of the X-linked RNA-binding protein RBMX promoted midlife increases in splenic miR-10a-5p, while complementary in vivo approaches supported a peripheral contribution to cerebral miR-10a-5p abundance. miR-10a-5p repressed calcium/calmodulin-responsive kinase γCaMKII, and modulation of this axis influenced mitochondrial function, cellular senescence, and memory in mice. In neurons derived from Alzheimer's disease patients and in model mice, miR-10a-5p inhibition attenuated disease-associated phenotypes, supporting relevance to pathological aging. Together, these findings link periphery-to-brain communication to emerging brain vulnerability during female midlife and indicate that this transition may remain amenable to intervention.

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A molecular pathway linking body signals to thinking problems in women during midlife

Abstract

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