Mechanisms of the interaction between aging of the male reproductive system and obesity, and clinical management strategies (Review)
4 affiliations
- 1Key Laboratory of Endocrine Glucose and Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250001, P.R. China
- 2Shandong Key Laboratory of Endocrine Metabolism and Aging, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250001, P.R. China
- 3Shandong Institute of Endocrine and Metabolic Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250001, P.R. China
- 4Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250001, P.R. China
Abstract
With the intensification of the aging of the global population, reproductive health problems among middle-aged and elderly males have emerged as a prominent public health issue. Late-onset hypogonadism (LOH), primarily induced by an age-related gradual reduction in serum testosterone, has garnered widespread clinical attention. The present review systematically elaborates the molecular and cellular mechanisms underlying testicular aging. Specifically, age-dependent alterations in Sertoli cells, interstitial cells and spermatogonial stem cells, as well as an imbalance in the testicular immune microenvironment, constitute the inherent pathological basis of testicular functional deterioration. A vicious cycle exists between obesity and testosterone deficiency: Obesity-triggered insulin resistance, chronic low-grade inflammation and oxidative stress directly inhibit testosterone synthesis and accelerate testicular aging; in turn, low testosterone levels promote visceral fat accumulation and insulin resistance, exacerbating obesity and metabolic disorders. Aging, obesity and testosterone deficiency synergistically drive the pathological progression of LOH. In terms of clinical intervention, the present review classifies the therapeutic strategies for testicular dysfunction induced by genetic, developmental and metabolic disorders based on etiological characteristics. The review also summarizes innovative therapeutic approaches targeting the testicular microenvironment and cellular senescence pathways, as well as frontier research hotspots, including natural product interventions and regenerative medicine. By integrating the interactive mechanisms of testicular aging and obesity and summarizing relevant multidimensional intervention strategies, this review provides a systematic theoretical basis for further exploring the pathogenesis and improving the clinical prevention and treatment system of LOH.
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BibTeX
@article{luo2026mechanisms,
title = {{Mechanisms of the interaction between aging of the male reproductive system and obesity, and clinical management strategies (Review)}},
author = {Dandan Luo and Lulu Zhang and Xiangyu Qi and Qiangbo Guan and Feng Xu and Peng Lu and Chunxiao Yu},
journal = {Molecular Medicine Reports},
year = {2026},
month = oct,
doi = {10.3892/mmr.2026.14051},
url = {https://doi.org/10.3892/mmr.2026.14051},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Mechanisms of the interaction between aging of the male reproductive system and obesity, and clinical management strategies (Review)
AU - Dandan Luo
AU - Lulu Zhang
AU - Xiangyu Qi
AU - Qiangbo Guan
AU - Feng Xu
AU - Peng Lu
AU - Chunxiao Yu
PY - 2026
DA - 2026/10/22
JO - Molecular Medicine Reports
DO - 10.3892/mmr.2026.14051
UR - https://doi.org/10.3892/mmr.2026.14051
AB - With the intensification of the aging of the global population, reproductive health problems among middle-aged and elderly males have emerged as a prominent public health issue. Late-onset hypogonadism (LOH), primarily induced by an age-related gradual reduction in serum testosterone, has garnered widespread clinical attention. The present review systematically elaborates the molecular and cellular mechanisms underlying testicular aging. Specifically, age-dependent alterations in Sertoli cells, interstitial cells and spermatogonial stem cells, as well as an imbalance in the testicular immune microenvironment, constitute the inherent pathological basis of testicular functional deterioration. A vicious cycle exists between obesity and testosterone deficiency: Obesity-triggered insulin resistance, chronic low-grade inflammation and oxidative stress directly inhibit testosterone synthesis and accelerate testicular aging; in turn, low testosterone levels promote visceral fat accumulation and insulin resistance, exacerbating obesity and metabolic disorders. Aging, obesity and testosterone deficiency synergistically drive the pathological progression of LOH. In terms of clinical intervention, the present review classifies the therapeutic strategies for testicular dysfunction induced by genetic, developmental and metabolic disorders based on etiological characteristics. The review also summarizes innovative therapeutic approaches targeting the testicular microenvironment and cellular senescence pathways, as well as frontier research hotspots, including natural product interventions and regenerative medicine. By integrating the interactive mechanisms of testicular aging and obesity and summarizing relevant multidimensional intervention strategies, this review provides a systematic theoretical basis for further exploring the pathogenesis and improving the clinical prevention and treatment system of LOH.
SN - 1791-2997
SN - 1791-3004
ER -