The Effects of Aging on Sperm Cells: Sperm Anti-Aging Protocol

Combatting the Effects of Aging on Sperm Cells: Sperm Anti-Aging Protocol

Sperm senescence refers to the process of aging and its associated decline in the quality and function of sperm cells. This concept encompasses various changes including decreased motility, increased DNA fragmentation, morphological abnormalities, and reduced fertilization capacity. As sperm cells age, they accumulate genetic and structural damage due to factors such as oxidative stress and environmental influences, which can impact their efficacy in successful fertilization and influence the health of potential offspring. Sperm senescence can contribute to decreased male fertility and an increased likelihood of genetic mutations or chromosomal abnormalities in the sperm, potentially leading to higher risks of birth defects or developmental disorders in children conceived with older paternal age.

Below are some of the processes which are affected by sperm senescence:

1. Decreased Sperm Production and Maturation (Spermatogenesis)

With age, there is a gradual decline in testosterone levels and changes in other hormonal balances (such as increased estrogen), which can decrease the rate of spermatogenesis. Testosterone supports the proliferation and differentiation of spermatogonia and the maturation of sperm cells. The reduction in the level of testosterone production is often attributed to the reduced efficacy of the Leydig cells. The decline not only lowers sperm production, but also affects libido and sexual function. Similarly, Sertoli cells also start losing their function as a response to aging. Sertoli cells are known as the nursing cells which provide nourishment 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 may also undergo structural changes and atrophy with age, further diminishing the efficiency of sperm production.

2. Genetic and Epigenetic Changes

The incidence of chromosomal anomalies, such as aneuploidy (abnormal number of chromosomes), increases in sperm from older men. This change is linked to errors in chromosome segregation during cell division. Age can also influence epigenetic marks on sperm DNA, such as DNA methylation patterns and histone modifications. These epigenetic changes can affect gene expression in the embryo and may have implications for the development and health of the offspring.

3. Oxidative Stress, Mitochondrial Function and DNA Integrity

Sperm DNA fragmentation rates increase with age. This fragmentation can result from oxidative stress and the decreased ability of sperm to repair DNA damage. Increased oxidative stress is common as men age due to a decline in antioxidant protection within the body. Oxidative stress can damage sperm DNA, proteins, and membranes, compromising sperm function.

Oxidative stress and mitochondrial function are intimately linked with sperm quality and are particularly relevant 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 because of their high content of polyunsaturated fatty acids in the plasma membrane and their limited intracellular reparative mechanisms.

In sperm, ROS are primarily generated as byproducts of normal metabolic processes occurring in mitochondria. Additional sources include leukocytes contaminated within semen and environmental factors such as toxins, smoking, and alcohol. Excessive ROS can lead to lipid peroxidation, damaging the sperm membrane, and can also cause DNA fragmentation and protein denaturation. This damage compromises sperm motility, viability, and the capacity to fertilize an 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, a necessary step for fertilization. As men age, mitochondrial function tends to decline due to damage accumulated over time and the reduced efficacy of mitochondrial DNA repair mechanisms. This decline can result in decreased ATP production, reducing sperm motility. Mitochondrial DNA (mtDNA) mutations also increase with age. These mutations can impair mitochondrial function further, exacerbating the energy deficit in sperm cells and potentially leading to increased generation of ROS.

The relationship between oxidative stress and mitochondrial function is cyclical. Mitochondrial dysfunction leads to an increase in ROS production, which in turn can cause further mitochondrial damage. This cycle is particularly detrimental to sperm quality in the following ways:

– Membrane Integrity: Oxidative stress damages the integrity of sperm membranes, crucial for maintaining the appropriate environment for enzyme activities and for receptor-mediated events during fertilization.

– DNA Integrity: Oxidative stress induces sperm DNA fragmentation. High DNA fragmentation rates are associated with reduced fertilization rates, poor embryo development, and lower 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 possess antioxidant defense mechanisms which include enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase, as well as non-enzymatic antioxidants like vitamin C, vitamin E, and glutathione. With advancing age, the efficacy of these antioxidant systems can diminish, leaving sperm more vulnerable to oxidative damage. Dietary and lifestyle factors can influence the levels of available antioxidants, potentially mitigating some effects of aging.

The decline in sperm quality with age is closely linked to increases in oxidative stress and decreases in mitochondrial function. The aging process exacerbates the natural vulnerability of sperm to oxidative damage, impacting mitochondrial efficiency, and reducing the fertilizing potential of sperm. These changes highlight the importance of addressing lifestyle factors that contribute to oxidative stress and considering antioxidant therapy as a potential strategy to improve sperm quality in aging males.

Sperm aging affects reproductive capacity through complex and multifaceted mechanisms that involve physiological, genetic, and molecular changes. These alterations can compromise the ability of sperm to effectively fertilize an egg and can also influence the health of the offspring. Understanding these factors is crucial for older men considering fatherhood, as it may influence decisions regarding timing and the use of assisted reproductive technologies.

While some of the damage caused by age cannot be undone, here at North Cyprus IVF Center, we have developed a specific protocol for restoring spermatogenic activity that can be attributed to senescence and aging in general.

This protocol makes use of certain lifestyle changes as well as supplements that are geared toward reduction of senescent cells, restoration of the anti-oxidant defense mechanism of the sperm cells, reduction of pro-inflammatory cytokines that are produced as a result of the inflammatory processes caused by senescent cells.

Sperm Anti-Aging Protocol:

Here’s a list of supplements that we use for their potential to modulate inflammation, reduce senescence and increase anti-oxidant activity of the sperm cells:

1- Omega-3 Fatty Acids (EPA and DHA)

Fish oil and krill oil are rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), omega-3 fatty acids known for their potent anti-inflammatory effects. Omega-3 fatty acids can interfere with the production of inflammatory eicosanoids and cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α).

2- Curcumin (Turmeric)

Curcumin is the active component of turmeric and has been widely studied for its anti-inflammatory properties. It inhibits key molecules that play a role in inflammation, including TNF-α, IL-1, and IL-6, mainly through the inhibition of the NF-kB pathway, which is a critical regulator of the immune response and inflammation.

3- Vitamin D

Vitamin D plays a critical role in modulating the immune system and suppressing the release of pro-inflammatory cytokines. It can modulate the immune response by reducing the production of pro-inflammatory cytokines and enhancing the expression of anti-inflammatory cytokines.

4. Fisetin

Fisetin is a bioactive flavonoid polyphenol that is found in various fruits and vegetables, including strawberries, apples, persimmons, onions, and cucumbers. It has garnered attention for its broad pharmacological properties, particularly its roles in anti-inflammatory, antioxidant, and anti-carcinogenic activities.

Fisetin, like other flavonoids, possesses potent antioxidant properties. It works primarily by scavenging free radicals, thus preventing oxidative stress, a condition that contributes to cellular damage and has been implicated in various chronic diseases including 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 pro-inflammatory cytokines such as TNF-α and IL-6. It modulates various signaling pathways, including those involving Nuclear Factor-kappa B (NF-κB), a protein complex that plays a significant 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 are key in the biosynthesis of pro-inflammatory mediators like prostaglandins and leukotrienes.

More recently, fisetin has been recognized for its potential senolytic activity, which means it can selectively induce death of senescent cells. Senescent cells are cells that have stopped dividing and contribute to aging and age-related diseases. By clearing away senescent cells, fisetin can potentially reduce or delay age-related tissue dysfunction and promote longevity.

5. NMN

Nicotinamide mononucleotide (NMN) plays a significant 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 to nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme in redox reactions that is vital for cellular energy production and numerous enzymatic processes in the body. Here’s how NMN impacts sperm cells:

Sperm motility relies heavily on energy provided by mitochondria, the powerhouses of the cell. NMN can enhance mitochondrial function by increasing NAD+ levels, which is crucial for the generation of ATP (adenosine triphosphate) through oxidative phosphorylation. Enhanced mitochondrial function translates into better sperm motility, which is essential for the successful journey of sperm to the egg in the fertilization process.

NMN can help mitigate oxidative stress in sperm cells by boosting the levels of NAD+, which in turn supports the activities of sirtuins and other antioxidant enzymes like superoxide dismutase (SOD) and catalase. These enzymes play a significant 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, reducing the occurrence of DNA fragmentation and improving the genetic quality of sperm. This is crucial for embryo development and reducing the risk of miscarriages and genetic abnormalities.

Sirtuins are a family of NAD+-dependent enzymes that are involved in cellular health maintenance, including DNA repair, gene expression regulation, and aging. NMN, by enhancing NAD+ levels, activates sirtuins. Activated sirtuins can improve sperm longevity and viability by promoting DNA repair mechanisms and regulating inflammatory responses within the reproductive tract.

6. GlyNAC

GlyNAC—a combination supplement consisting of glycine and N-acetylcysteine (NAC)—has garnered attention for its potential benefits in overall health due to its role in boosting glutathione levels, a critical antioxidant in the body. Its impact on sperm cells can 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 serves as a precursor to cysteine, which is a limiting substrate for the synthesis of glutathione. Glycine, also part of the GlyNAC supplement, is another component required for the synthesis of glutathione. Together, they ensure the availability of essential substrates for glutathione production.

Sperm are particularly vulnerable to oxidative stress due to their high concentration of polyunsaturated fatty acids and their relatively scant cytoplasmic volume, which contains fewer defensive enzymes against oxidative stress. By enhancing glutathione levels, GlyNAC can help protect sperm from oxidative damage, thereby improving sperm motility and integrity. This protection extends to the sperm DNA, reducing the incidence 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, crucial factors for successful fertilization. Improved antioxidant capacity through enhanced glutathione levels may help maintain DNA integrity in sperm cells, critical for successful fertilization and normal embryo development.

Beyond its role in antioxidant defense, glutathione can modulate the inflammatory response. NAC has been shown to influence cytokine production, potentially reducing inflammation that can adversely affect sperm production and health.

Not every patient is prescribed all of these supplements and the dosage, and the length of usage is tailored to each individual patient. We do NOT recommend just any brand of supplements. Supplements need to come from companies that are GMP-compliant, and third party tested. Therefore, we only recommend the following brands:

1- Do-Not-Age: This brand comes up at number one on the supplement companies list due to purity of its products. If purchasing from this company, don’t forget to use ELITE10 as your coupon code for a 10% discount.

2- VitalityPRO: This brand is also third-party tested and transparent about its products purity. If purchasing from this company, don’t forget to use ELITE10 as your coupon code for a 10% discount.

3- Nature’s Fusions: If purchasing your products from the United States, Nature’s fusions is one of the best suppliers which guarantees purity. You will need to contact them for a discount code before placing a purchase by mentioning you have been referred by Dr. Ahmet Ozyigit at Elite Hospital.

Keep in mind that self-supplementing is not going to optimize your results unless you are given a regimen by our fertility specialists that is geared specifically to your own needs. The information contained on this website aims to provide you with a general understanding of factors influencing male fertility and some solutions that can provide benefits in combatting age-related decline in fertility. However, the information on its own, without expert consultation should not, in any way, interpreted as medical advice.