Sex-specific gene and isoform expression characterizes hippocampal aging in rhesus macaques

In 24 aging rhesus macaques, short- and long-read hippocampal RNA-seq revealed 594 age-associated differential isoform expression events, including sex-specific changes.

• Why it matters: Aging-related cognitive decline and inflammaging are linked to inflammatory and glial alterations, but the biological significance of isoform-level changes in the aging brain is unclear.
• What they did: The study used short- and long-read RNA sequencing across sex, then applied WGCNA to find sex-specific modules and compared rhesus networks with a human hippocampal AD single-nucleus dataset (GSE268609).
• The result: Inflammatory pathways (including TNF- NF-{kappa}B signaling, interferon responses, and complement) were enriched across sexes, and cross-species module preservation with gene overlap implicated shared glial, inflammation, and mitochondrial biology.

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