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14 January 2026

Organ-Specific Regulation of Systemic Aging: Focus on the Brain, Skeletal Muscle, and Gut

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1
Institute of Visual Neuroscience and Stem Cell Engineering, Wuhan University of Science and Technology, Wuhan 430065, China
2
College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan 430065, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.

Abstract

As global population aging accelerates, the growing burden of age-related diseases is driving a shift in medical research from single-disease treatment to interventions targeting the aging process itself. Organ-specific interventions have emerged as a promising strategy to modulate systemic aging. Among organs, the brain, muscle, and gut have attracted particular attention due to their central roles in neural regulation, metabolic homeostasis, and immune balance. In this review, we focus on these three key organs, systematically summarizing their roles and regulatory mechanisms in organismal aging and discussing how exercise influences the aging process by affecting these organs. Crucially, we propose a novel “local-to-global” regulatory model, positing that preserving homeostasis in these specific tissues is sufficient to orchestrate systemic anti-aging effects. This work represents a conceptual advance by providing the theoretical rationale to move beyond non-specific systemic treatments toward precise, organ-targeted interventions.

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