A Multi-Omic Atlas In The African Turquoise Killifish Reveals Increased Glucocorticoid Signaling As A Hallmark Of Brain Aging
Aging is a primary factor contributing to cognitive decline and neurodegenerative diseases, yet the underlying molecular processes in the brain remain largely unclear. To shed light on these changes, scientists have utilized the African turquoise killifish, a vertebrate with a naturally short lifespan, as an accelerated model for studying brain aging.
Researchers developed a detailed “atlas” of brain aging in these fish, examining changes in gene activity and regulation over time. A significant finding was the expansion of microglia, the brain’s immune cells, in older fish, which shifted towards a more inflammatory state. Crucially, the study identified that heightened glucocorticoid signaling—a pathway involving stress hormones like cortisol—acts as a major driver of these age-related alterations in the brain.
Remarkably, when this glucocorticoid signaling was pharmacologically inhibited starting in middle age, it led to a significant reversal of several molecular and cellular signs of brain aging. This suggests that targeting the stress hormone pathway could be a promising strategy for developing interventions to combat brain aging and its associated impairments.
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