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

## TL;DR

This paper reviews how the brain, muscle, and gut regulate aging and how exercise can slow aging by maintaining balance in these organs.

## Contribution

It introduces a new 'local-to-global' model suggesting that maintaining organ-specific homeostasis can drive systemic anti-aging effects.

## Key findings

- The brain, muscle, and gut play central roles in regulating systemic aging through neural, metabolic, and immune pathways.
- Exercise mitigates aging by modulating these three organs' homeostasis.
- A novel 'local-to-global' model proposes that preserving organ-specific balance can orchestrate systemic anti-aging effects.

## Abstract

What are the main findings?
This review systematically elucidates the regulatory mechanisms of three critical target organs—the brain, muscle, and gut—in organismal aging and analyzes how exercise mitigates the aging process by modulating these tissues.We propose a novel “local-to-global” regulatory model, positing that preserving homeostasis within these specific tissues is sufficient to orchestrate systemic anti-aging effects via neural, metabolic, and immune pathways.

This review systematically elucidates the regulatory mechanisms of three critical target organs—the brain, muscle, and gut—in organismal aging and analyzes how exercise mitigates the aging process by modulating these tissues.

We propose a novel “local-to-global” regulatory model, positing that preserving homeostasis within these specific tissues is sufficient to orchestrate systemic anti-aging effects via neural, metabolic, and immune pathways.

What are the implication of the main findings?
The study offers a conceptual advance that supports a paradigm shift in medical research, moving away from non-specific systemic treatments toward precise, organ-targeted interventions.These insights provide a critical theoretical rationale for developing novel therapeutic strategies that target organ-specific homeostasis to combat age-related multimorbidity and extend healthy longevity.

The study offers a conceptual advance that supports a paradigm shift in medical research, moving away from non-specific systemic treatments toward precise, organ-targeted interventions.

These insights provide a critical theoretical rationale for developing novel therapeutic strategies that target organ-specific homeostasis to combat age-related multimorbidity and extend healthy longevity.

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.