Current Status And Prospects Of TCM in Delaying Male Reproductive Aging
Aug 29, 2024
Abstract This article reviews the mechanism of TCM in delaying male reproductive aging in combination with modern medical research. TCM believes that the rise and fall of kidney essence is closely related to male reproductive function. Modern medicine believes that male reproductive aging is related to decreased testosterone levels, decreased sperm quality, and changes in epididymal inflammatory characteristics. This article lists the mechanisms of inhibiting reproductive aging of male rats or mice by single effective ingredients of Chinese medicine such as Angelica polysaccharide, puerarin, total flavonoids of Epimedium, Cistanche, notoginseng saponins, ginsenosides, tanshinone, resveratrol, etc., as well as compound Chinese medicine Wuzi Yanzong Pills, He Shouwu Drink, and Dahuang Shuchong Pills. In addition, electroacupuncture and moxibustion can also delay reproductive aging in rats. TCM has certain advantages in delaying male reproductive aging.
Keywords Male reproductive aging; TCM; Literature review
Male reproductive aging refers to the process of gradual decline in the structure and function of the male reproductive system. Male reproductive aging can be physiological aging caused by age factors, but more often it is pathological aging caused by other pathogenic factors that accelerate the development of reproductive system aging, such as oxidative stress, mitochondrial dysfunction, telomere shortening, genetic changes, etc. [1] due to the fast pace of life, high pressure, irregular diet and work and rest habits of people in modern society. Numerous pathogenic factors cause the male reproductive system to gradually lose its physiological integrity and normal function, which is mainly manifested in the decline of endocrine function and spermatogenesis, resulting in a series of male diseases such as decreased sperm quality, male late-onset hypogonadism, and sexual dysfunction. Traditional Chinese medicine has rich theoretical and practical experience in delaying reproductive aging. This article will review the research on traditional Chinese medicine in delaying male reproductive aging in combination with modern medicine.
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1 TCM's understanding of male reproductive aging
The rise and fall of kidney essence is closely related to male reproductive function. As early as in the Suwen Shanggu Tianzhen Lun, there was a relatively detailed understanding of male reproductive aging, "At the age of 58, the kidney qi declines, the hair falls out, and the teeth dry up... At the age of 88, the teeth and hair fall out." Generally speaking, men enter the aging period after the age of 40, the Yangming pulse gradually declines, the Tiangui gradually exhausts, the body ages, the essence gradually depletes, and the reproductive ability gradually declines. At around the age of 64, the kidney qi declines, the Tiangui is exhausted, and the reproductive ability is lost. At the same time, the article also discusses the special cases of "being able to delay aging and keep the body intact" and "having children at the age of 100". "The prosperity and decline of a person all originate from the kidneys." Traditional Chinese medicine believes that delaying reproductive aging should start with replenishing kidney essence and kidney qi to replenish Tiangui. Studies have shown that kidney-tonifying prescriptions can play an anti-aging role in many aspects, such as oxidative stress, endoplasmic reticulum stress response, stem cell proliferation and differentiation, immune enhancement, and neuroprotection [2]. The essence and qi in the kidney also depend on the nourishment of the essence and qi of the five internal organs. "The kidney governs water, receives and stores the essence of the five internal organs and six bowels." A study of the composition and medication patterns of 530 anti-aging prescriptions in 87 ancient Chinese medical books from the Han Dynasty to the Qing Dynasty also found that the drugs in ancient anti-aging prescriptions mainly enter the kidney meridian, followed by the liver, spleen, heart, lung, and stomach meridians, and mainly enter the five internal organs and the stomach [3]. This shows that the rise and fall of the essence in the kidney is closely related to the rise and fall of the essence in the five internal organs and six bowels. While nourishing the kidney, we should not ignore the cultivation of the essence of the five internal organs and six bowels.
2 Modern medicine's understanding of male reproductive aging
2.1 The impact of male reproductive aging on testosterone levels
Modern medical research believes that testosterone is a key factor in maintaining normal reproductive and sexual function, and reproductive system aging is mainly caused by a decrease in serum testosterone levels [4]. Leydig cells (LC) are the main cells that produce testosterone in men [5]. During aging, the ability of LC to synthesize testosterone gradually decreases. Leydig stem cells (SLCs) in the testicular interstitium can proliferate and differentiate into functional LCs [6]. The absence of nestin reduces the differentiation ability of SLCs by separating mitochondria-endoplasmic reticulum contacts (MERCs), thereby leading to male reproductive aging [7].
Increased levels of reactive oxygen species (ROS) can lead to stem cell aging [8]. Aging and the presence of macrophages can significantly affect the proliferation and differentiation of SLCs [9]. The activity of p38 MAPK in the body increases with age, which promotes LC aging, leading to reduced testosterone synthesis and the occurrence of late-onset hypogonadism (LOH) in men [10].
2.2 Effects of male reproductive aging on sperm quality Decreased sperm quality is one of the important manifestations of male reproductive aging. A retrospective study of semen quality of more than 5,000 men aged 16 to 72 found that semen quality began to decline after the age of 34 [11]. DNA damage caused by oxidative stress is the main cause of sperm dysfunction [12]. Increased production of ROS and reduced supply of antioxidants disrupt the oxidative balance in the body, thereby affecting the HPG axis and leading to reduced secretion of reproductive hormones, resulting in a series of symptoms of reproductive aging [13]. Excessive ROS causes various types of damage, making sperm cells unable to fertilize oocytes; at the same time, the increasing oxidative stress will cause changes in the metabolic rate of sperm during storage, ultimately affecting male reproductive health [14]. MicroRNA (miRNA) plays an important role in regulating sperm function in aging men. Abnormally increased miRNA in sperm affects sperm function by damaging sperm DNA and affects early embryonic development; abnormally increased miRNA also reduces ATP production by damaging the respiratory chain, leading to mitochondrial dysfunction and ultimately leading to sperm abnormalities [15]. The decline in sperm motility in aging men is associated with the upregulation of miＲ-574 in sperm. miＲ-574 inhibits mitochondrial function and reduces ATP production by directly targeting mt-ND5 [16]. miＲ-125a-5p
In an aging model, it induces embryonic developmental delay at a specific morula/blastocyst stage in a p21-dependent manner [17]. Studies have found that citrate and oxidative phosphorylation in the elderly are downregulated, resulting in reduced ATP synthesis and thus decreased sperm motility; decreased carnitine content in the body leads to abnormal fatty acid metabolism in sperm; reduced levels of two major antioxidants, reduced glutathione and oxidized glutathione, lead to an imbalance in the body's oxidative reaction, impairing the integrity of the sperm plasma membrane and DNA, thus causing male infertility [18]. In addition, aging can cause epigenetic changes, which affect the level of histone modification in sperm during the process of development to varying degrees [19].
2 Modern medicine's understanding of male reproductive aging
2.1 The impact of male reproductive aging on testosterone levels
Modern medical research believes that testosterone is a key factor in maintaining normal reproductive and sexual function, and reproductive system aging is mainly caused by a decrease in serum testosterone levels [4]. Leydig cells (LC) are the main cells that produce testosterone in men [5]. During aging, the ability of LC to synthesize testosterone gradually decreases. Leydig stem cells (SLCs) in the testicular interstitium can proliferate and differentiate into functional LCs [6]. The absence of nestin reduces the differentiation ability of SLCs by separating mitochondria-endoplasmic reticulum contacts (MERCs), thereby leading to male reproductive aging [7].
Increased levels of reactive oxygen species (ROS) can lead to stem cell aging [8]. Aging and the presence of macrophages can significantly affect the proliferation and differentiation of SLCs [9]. The activity of p38 MAPK in the body increases with age, which promotes LC aging, leading to reduced testosterone synthesis and the occurrence of late-onset hypogonadism (LOH) in men [10].
2.2 Effects of male reproductive aging on sperm quality Decreased sperm quality is one of the important manifestations of male reproductive aging.
A retrospective study of semen quality of more than 5,000 men aged 16 to 72 found that semen quality began to decline after the age of 34 [11]. DNA damage caused by oxidative stress is the main cause of sperm dysfunction [12]. Increased production of ROS and reduced supply of antioxidants disrupt the oxidative balance in the body, thereby affecting the HPG axis and leading to reduced secretion of reproductive hormones, resulting in a series of symptoms of reproductive aging [13]. Excessive ROS causes various types of damage, making sperm cells unable to fertilize oocytes; at the same time, the increasing oxidative stress will cause changes in the metabolic rate of sperm during storage, ultimately affecting male reproductive health [14]. MicroRNA (miRNA) plays an important role in regulating sperm function in aging men. Abnormally increased miRNA in sperm affects sperm function by damaging sperm DNA and affects early embryonic development; abnormally increased miRNA also reduces ATP production by damaging the respiratory chain, leading to mitochondrial dysfunction and ultimately leading to sperm abnormalities [15]. The decline in sperm motility in aging men is associated with the upregulation of miＲ-574 in sperm. miＲ-574 inhibits mitochondrial function and reduces ATP production by directly targeting mt-ND5 [16]. miＲ-125a-5p
In an aging model, it induces embryonic developmental delay at a specific morula/blastocyst stage in a p21-dependent manner [17]. Studies have found that citrate and oxidative phosphorylation in the elderly are downregulated, resulting in reduced ATP synthesis and thus decreased sperm motility; decreased carnitine content in the body leads to abnormal fatty acid metabolism in sperm; reduced levels of two major antioxidants, reduced glutathione and oxidized glutathione, lead to an imbalance in the body's oxidative reaction, which damages the integrity of sperm plasma membrane and DNA, thus causing male infertility [18]. In addition, aging can cause epigenetic changes, which affect the level of histone modification during spermatogenesis to varying degrees [19].
2.3 Effects of male reproductive aging on the epididymis
The aging of testicular function is the focus of current research on reproductive aging. In fact, other components of the reproductive system, including the vas deferens (epididymis, vas deferens, ejaculatory ducts and urethra), accessory glands (spermatic vesicles, prostate, bulbourethral glands), and the decline in the structure and function of the scrotum and penis also fall within the scope of research on male reproductive aging. A study of the epididymal initial segment (IS) in a naturally aged mouse model using single-cell RNA sequencing found that the aged epididymal IS exhibited inflammatory characteristics, with inflammatory cell infiltration, cytokine secretion, immune cell infiltration, and increased pro-inflammatory molecule expression profiles, providing a theoretical basis for delaying male reproductive aging through immune regulation in the future [20].
2.1 Basic Characteristics
The incidence of depression, anxiety, and stress symptoms in 582 male college students in Chongqing was 6.70%, 12.71%, and 6.70% respectively, and the proportion of sitting for less than 6 hours, 6-10 hours, and more than 10 hours per day was 31.96%, 57.04%, and 11.00% respectively, see Table 1.
