Combating the Effects of Aging on Sperm Cells: Sperm Anti-Aging Protocol
Sperm senescence refers to the aging process and the associated decline in the quality and function of sperm cells. This concept encompasses a variety of changes such as decreased motility, increased DNA fragmentation, morphological abnormalities and reduced fertilization capacity. As sperm cells age, genetic and structural damage accumulates due to factors such as oxidative stress and environmental influences, which can affect the efficiency of sperm cells in successful fertilization and affect the health of potential offspring. Sperm aging can contribute to reduced male fertility and an increased likelihood of genetic mutations or chromosomal abnormalities in sperm, potentially leading to an increased risk of birth defects or developmental disorders in children conceived with older paternal age.
Below are some of the processes affected by sperm aging:
- Decreased Sperm Production and Maturation (Spermatogenesis)
With age, there is a gradual decline in testosterone levels and changes in other hormonal balances (such as an increase in estrogen), which can reduce the rate of spermatogenesis. Testosterone supports the proliferation and differentiation of spermatogonia and the maturation of sperm cells. A decrease in the level of testosterone production is usually attributed to reduced activity of Leydig cells. The decline not only reduces sperm production, but also affects libido and sexual function. Similarly, Sertoli cells begin to lose their function in response to aging. Sertoli cells are known as maintenance cells that provide nutritional and structural support to developing sperm cells.
Cellular senescence refers to an age-related increase in apoptosis (programmed cell death). Higher apoptotic activity among sperm cells can further reduce the overall output of sperm cells. This is partly due to increased oxidative stress and DNA damage in older cells.
The testes can also undergo structural changes and atrophy with age, which can further reduce the efficiency of sperm production.
- Genetic and Epigenetic Changes
Older men have an increased incidence of chromosomal abnormalities in their sperm, such as aneuploidy (abnormal chromosome number). This change is linked to errors in chromosome segregation during cell division. Age can also affect epigenetic markers in sperm DNA, such as DNA methylation patterns and histone modifications. These epigenetic changes can affect gene expression in the embryo and have implications for the development and health of the offspring.
- Oxidative Stress, Mitochondrial Function and DNA Integrity
Sperm DNA fragmentation rates increase with age. This fragmentation can be caused by oxidative stress and a reduced ability of sperm to repair DNA damage. Increased oxidative stress is common as men age due to decreased antioxidant protection in the body. Oxidative stress can damage sperm DNA, proteins and membranes, compromising sperm function.
Oxidative stress and mitochondrial function are closely linked to sperm quality and are particularly important when considering the effects of aging on male fertility. Oxidative stress results from an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defenses available to neutralize them. Spermatozoa are particularly susceptible to oxidative stress due to their high content of polyunsaturated fatty acids in the plasma membrane and limited intracellular reparative mechanisms.
ROS in sperm are produced primarily as by-products of normal metabolic processes occurring in mitochondria. Additional sources include contaminated leukocytes and toxins in semen, environmental factors such as smoking and alcohol. Excess ROS can damage the sperm membrane, leading to lipid peroxidation and can also cause DNA fragmentation and protein denaturation. This damage compromises sperm motility, viability and the capacity to fertilize the egg.
Mitochondria play a critical role in energy production through the process of oxidative phosphorylation. In sperm cells, mitochondria are crucial for providing the energy required for motility and for the successful completion of the acrosome reaction, an essential step for fertilization. As men age, mitochondrial function tends to decline due to accumulated damage over time and reduced efficiency of mitochondrial DNA repair mechanisms. This decline can lead to reduced ATP production and reduced sperm motility. Mitochondrial DNA (mtDNA) mutations also increase with age. These mutations can further impair mitochondrial function, exacerbate the energy deficit in sperm cells and potentially lead to increased ROS production.
The relationship between oxidative stress and mitochondrial function is cyclical. Mitochondrial dysfunction leads to increased ROS production, which in turn can cause further mitochondrial damage. This cycle is particularly damaging to sperm quality in the following ways:
- Membrane Integrity: Oxidative stress damages the integrity of sperm membranes, which is crucial for maintaining a favorable environment for enzyme activities and receptor-mediated events during fertilization.
- DNA Integrity: Oxidative stress causes sperm DNA fragmentation. High rates of DNA fragmentation are associated with low fertilization rates, poor embryo development and low pregnancy rates.
- Apoptosis: Increased oxidative stress can trigger apoptosis in sperm cells, reducing sperm count and affecting overall semen quality.
To combat oxidative stress, sperm have antioxidant defense mechanisms that include enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase, as well as non-enzymatic antioxidants such as vitamin C, vitamin E and glutathione. With advancing age, the effectiveness of these antioxidant systems may decrease and sperm may become more vulnerable to oxidative damage. Dietary and lifestyle factors can potentially mitigate some of the effects of aging by influencing the levels of available antioxidants.
The decline in sperm quality with age is closely linked to increased oxidative stress and reduced mitochondrial function. The aging process increases the natural sensitivity of sperm to oxidative damage, affecting mitochondrial efficiency and reducing the fertilization potential of sperm. These changes highlight the importance of addressing lifestyle factors that contribute to oxidative stress and evaluating antioxidant therapy as a potential strategy to improve sperm quality in aging men.
Sperm aging affects reproductive capacity through complex and multifaceted mechanisms involving physiological, genetic and molecular changes. These changes can compromise the sperm’s ability to fertilize the egg effectively and can also affect the health of the offspring. Understanding these factors is crucial for older men considering becoming fathers because it can influence decisions about timing and the use of assisted reproductive technologies.
While some of the damage caused by age is irreversible, at the North Cyprus IVF Center, we have developed a special protocol to restore spermatogenic activity that can be attributed to aging and aging in general.
This protocol utilizes specific lifestyle changes as well as supplements aimed at the reduction of senescent cells, restoration of the antioxidant defense mechanism of sperm cells, reduction of pro-inflammatory cytokines produced as a result of inflammatory processes caused by senescent cells
Sperm Yaşlanma Karşıtı Protokol:
Enflamasyonu modüle etme, yaşlanmayı azaltma ve sperm hücrelerinin antioksidan aktivitesini artırma potansiyelleri nedeniyle kullandığımız takviyelerin bir listesi:
1- Omega-3 Yağ Asitleri (EPA ve DHA)
Balık yağı ve kril yağı, güçlü anti-inflamatuar etkileriyle bilinen omega-3 yağ asitleri olan eikosapentaenoik asit (EPA) ve dokosaheksaenoik asit (DHA) açısından zengindir. Omega-3 yağ asitleri, interlökin-1 (IL-1) ve tümör nekroz faktörü-alfa (TNF-α) gibi inflamatuar eikosanoidlerin ve sitokinlerin üretimine müdahale edebilir.
2- Kurkumin (Zerdeçal)
Kurkumin, zerdeçalın aktif bileşenidir ve antiinflamatuar özellikleri nedeniyle geniş çapta araştırılmıştır. TNF-a, IL-1 ve IL-6 dahil olmak üzere iltihaplanmada rol oynayan anahtar molekülleri, esas olarak bağışıklık tepkisi ve iltihaplanmanın kritik bir düzenleyicisi olan NF-kB yolunun inhibisyonu yoluyla inhibe eder.
3- Vitamin D
Vitamin D plays a critical role in modulating the immune system and suppressing the release of proinflammatory cytokines. It can modulate the immune response by reducing the production of proinflammatory cytokines and increasing the expression of anti-inflammatory cytokines.
4.Fisetin
Fisetin is a bioactive flavonoid polyphenol found in a variety of fruits and vegetables, including strawberries, apples, persimmons, onions and cucumbers. It has attracted attention for its broad pharmacological properties, particularly for its roles in anti-inflammatory, antioxidant and anti-carcinogenic activities.
Fisetin, like other flavonoids, has strong antioxidant properties. It works primarily by scavenging free radicals, thus preventing oxidative stress, a condition that contributes to cellular damage and plays a role in various chronic diseases such as cancer, neurodegeneration and heart disease. By reducing oxidative stress, fisetin helps maintain the integrity of cells and tissues, enhancing cellular function and longevity.
Fisetin can inhibit the production and activity of proinflammatory cytokines such as TNF-α and IL-6. It modulates several signaling pathways, including those involving Nuclear Factor-kappa B (NF-κB), a protein complex that plays an important role in controlling DNA transcription and cell survival. Fisetin also inhibits the activities of enzymes involved in the inflammatory process, such as cyclooxygenase (COX) and lipoxygenase (LOX), which play key roles in the biosynthesis of proinflammatory mediators such as prostaglandins and leukotrienes.
More recently, fisetin has been recognized for its potential senolytic activity, meaning that it can selectively induce the death of senescent cells. Senescent cells are cells that stop dividing and contribute to aging and age-related diseases. By clearing senescent cells, fisetin may potentially reduce or delay age-related tissue dysfunctions and promote longevity.
5.NMN
Nicotinamide mononucleotide (NMN) plays an important role in cellular metabolism and energy production and has implications for various biological functions, including the health and functionality of sperm cells. NMN is a precursor of nicotinamide adenine dinucleotide (NAD+), an essential coenzyme in redox reactions that are vital for cellular energy production and numerous enzymatic processes in the body. Here is how NMN affects sperm cells:
Sperm motility relies heavily on the energy provided by mitochondria, the powerhouses of the cell. NMN can improve mitochondrial function by increasing levels of NAD+, which is crucial for ATP (adenosine triphosphate) production through oxidative phosphorylation. Improved mitochondrial function means better sperm motility, which is essential for the successful journey of sperm to the egg during the fertilization process.
NMN may help reduce oxidative stress in sperm cells by increasing NAD+ levels, which supports the activities of sirtuins and other antioxidant enzymes such as superoxide dismutase (SOD) and catalase. These enzymes play an important role in detoxifying reactive oxygen species (ROS) that can damage sperm DNA, proteins, and lipids. Lower levels of oxidative stress help maintain the integrity of sperm DNA, reduce the occurrence of DNA fragmentation, and improve the genetic quality of sperm. This is crucial for embryo development and reducing the risk of miscarriage and genetic abnormalities.
Sirtuins are a family of NAD+-dependent enzymes that play a role in maintaining cellular health, including DNA repair, gene expression regulation, and aging. NMN activates sirtuins by increasing NAD+ levels. Activated sirtuins may increase sperm lifespan and viability by promoting DNA repair mechanisms and regulating inflammatory responses in the reproductive system.
- GlyNAC
GlyNAC (a combination supplement consisting of glycine and N-acetylcysteine (NAC)) has attracted attention for its potential health benefits due to its role in increasing levels of glutathione, a critical antioxidant in the body. Its effects on sperm cells may be significant, especially considering the susceptibility of sperm to oxidative stress and the importance of antioxidants in maintaining sperm health.
Glutathione is a tripeptide composed of glycine, cysteine, and glutamic acid. It is one of the most important antioxidants in human cells, protecting cells from oxidative damage caused by reactive oxygen species (ROS). NAC acts as a precursor to cysteine, a limiting substrate for glutathione synthesis. Glycine, which is part of the GlyNAC supplement, is another ingredient needed for the synthesis of glutathione. Together, they ensure the availability of the necessary substrates for glutathione production.
Sperm are particularly vulnerable to oxidative stress due to their relatively scant cytoplasmic volume, which contains a high concentration of polyunsaturated fatty acids and fewer oxidative stress defense enzymes. GlyNAC may help protect sperm from oxidative damage by increasing glutathione levels, thereby improving sperm motility and integrity. This protection extends to sperm DNA, reducing the likelihood of DNA fragmentation.
Oxidative stress can negatively impact sperm motility and cause morphological abnormalities. By reducing oxidative stress, GlyNAC may help maintain normal sperm motility and morphology, which are important factors for successful fertilization. Enhanced antioxidant capacity through increased glutathione levels may help maintain DNA integrity in sperm cells, which is critical for successful fertilization and normal embryo development.
Beyond its role in antioxidant defense, glutathione can modulate inflammatory responses. NAC has been shown to affect cytokine production, potentially reducing inflammation that can negatively impact sperm production and health.
Not all of these supplements and their dosages are prescribed to every patient, and the duration of use is adapted to each patient. We do not recommend any brand of supplements. Supplements must come from companies that are GMP compliant and third-party tested. Therefore, we only recommend the following brands:
1- Aging: This brand is number one on the list of dietary supplement companies due to the purity of its products. If you are purchasing from this company, do not forget to use ELITE10 as your coupon code for a 10% discount.
2- VitalityPRO: This brand is also third-party tested and transparent about the purity of its products. If you are purchasing from this company, do not forget to use ELITE10 as your coupon code for a 10% discount.
3- Nature’s Fusions: If you are purchasing your products from the United States, Nature’s Fusions is one of the best suppliers that guarantees purity. Before shopping, you must contact us to get a discount code by stating that you were referred by Dr. Ahmet Özyiğit from Elite Hospital.
Please note that self-supplementation will not optimize your results unless a regimen has been specifically tailored to your needs by our fertility experts. The information on this website is intended to provide a general understanding of the factors that affect male fertility and some solutions that may be helpful in combating age-related fertility decline. However, the information provided should not be construed as medical advice without seeking expert advice.