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Review
. 2024 Jan 17:15:1291389.
doi: 10.3389/fendo.2024.1291389. eCollection 2024.

A narrative review on inflammaging and late-onset hypogonadism

Dong Xing  1 , Yihan Jin  2 , Baofang Jin  3
Affiliations
Review

A narrative review on inflammaging and late-onset hypogonadism

Dong Xing et al. Front Endocrinol (Lausanne). .

Abstract

The increasing life expectancy observed in recent years has resulted in a higher prevalence of late-onset hypogonadism (LOH) in older men. LOH is characterized by the decline in testosterone levels and can have significant impacts on physical and mental health. While the underlying causes of LOH are not fully understood, there is a growing interest in exploring the role of inflammaging in its development. Inflammaging is a concept that describes the chronic, low-grade, systemic inflammation that occurs as a result of aging. This inflammatory state has been implicated in the development of various age-related diseases. Several cellular and molecular mechanisms have been identified as contributors to inflammaging, including immune senescence, cellular senescence, autophagy defects, and mitochondrial dysfunction. Despite the extensive research on inflammaging, its relationship with LOH has not yet been thoroughly reviewed in the literature. To address this gap, we aim to review the latest findings related to inflammaging and its impact on the development of LOH. Additionally, we will explore interventions that target inflammaging as potential treatments for LOH.

Keywords: Leydig cell; inflammaging; late-onset hypogonadism (LOH); mitochondrial; senescence-associated secretory phenotype (SASP).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Diagram illustrating the influence of immune senescence-induced inflammaging on testosterone synthesis in Leydig cells. Aging profoundly affects peripheral blood immune cells, inducing notable alterations in T cells, NK cells, dendritic cells, monocytes, and macrophages. This shift leads to an elevated presence of pro-inflammatory immune cells and an excessive production of pro-inflammatory cytokines, subsequently influencing the regular functionality of the hypothalamic-pituitary-gonadal (HPG) axis via the circulatory system. Testicular macrophages, under the influence of senescence, transition towards the M1 subtype (hyperactivated), characterized by heightened secretion of abundant pro-inflammatory factors. These factors are then released through paracrine signaling, directly impacting the functionality of Leydig cells.
Figure 2
Figure 2
Illustrates the schematic depiction of senescence-induced alterations in Leydig cells. Leydig cell senescence manifests a spectrum of modifications, encompassing cell cycle arrest, the emergence of senescence-associated secretory phenotypes (SASP), mitochondrial dysfunction, and autophagy deficiency. These alterations also play a crucial role in the development of testicular inflammaging, leading to substantial inhibition of Leydig cell function.
Figure 3
Figure 3
Schematic representation depicting the interrelation between inflammaging and late-onset hypogonadotropic hypogonadism (LOH). As aging progresses, alterations in peripheral blood immune cells, testicular macrophages, and Leydig cells become pronounced, creating a milieu of widespread and localized inflammation. This state, termed inflammaging, disrupts the intricate process of testosterone synthesis within Leydig cells, consequently initiating and advancing the development of LOH in aging males.
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Publication types

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (Grant No. 82074440, 82004376).
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