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Exercise Improves Cardiac Dysfunction in D-Galactose-Treated Rats by Regulation of IGF-1-Humanin Pathway.

Hesam Askarimoghadam¹, Farzaneh Rostamzadeh², Maryamossadat Mirtajaddini Goki³

¹Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.

Journal of Aging Research

|October 6, 2025

Summary

Moderate-intensity endurance training (MIET) and high-intensity interval training (HIIT) can improve cardiac function in aging rats by boosting humanin and IGF-1 levels, suggesting a role for the IGF-1-humanin pathway.

Keywords:

D-galactose IGF-1 heart high-intensity interval training humanin moderate-intensity endurance training

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Area of Science:

Cardiovascular Physiology
Aging Research
Exercise Science

Background:

Humanin, a peptide from mitochondria, declines with age, impacting cardiac health.
D-galactose injection in rats mimics aging-related cardiac dysfunction.
Exercise interventions are explored to counteract age-related cardiac decline.

Purpose of the Study:

To investigate the effects of MIET and HIIT on cardiac function in D-galactose-induced aging rat models.
To assess the impact of exercise on serum and heart levels of humanin and IGF-1.
To elucidate the role of the IGF-1-humanin signaling pathway in exercise-mediated cardioprotection.

Main Methods:

Wistar male rats were divided into control, exercise-only, and D-galactose-induced aging groups.
Groups received either MIET or HIIT concurrently with D-galactose injection.
Cardiac function (LVSP, LVEDP, ±maxdp/dt, CI, Tau), histopathology, fibrosis, and humanin/IGF-1 levels were measured.

Main Results:

D-galactose injection impaired cardiac function and increased cardiac fibrosis and histopathological scores.
Both MIET and HIIT interventions attenuated cardiac dysfunction and reduced fibrosis in D-galactose-treated rats.
Exercise training significantly increased serum and heart humanin levels, correlating with modified IGF-1 levels.

Conclusions:

HIIT and MIET effectively improve cardiac function in a rat model of aging.
Exercise interventions appear to enhance cardiac health by modulating the IGF-1-humanin signaling pathway.
The findings highlight the therapeutic potential of exercise in mitigating age-related cardiac decline.