The Male Biological Clock

Written By Dr. Burns

Featured post by: Kristin Brogaard, PhD www.pathfertility.com

For years, when discussing age and fertility, the focus has been on the woman’s biological clock. However, a growing foundation of data now suggests that men have biological clocks, too. While it is true that men can produce sperm until their dying day, it does not mean that their sperm is functioning well on a biological level.

As a man ages there are several key issues they should consider when considering having a child.

Older men have been shown to have:

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Interestingly, the effect of age and lifestyle on sperm quality and function is unique for each man. It is important to understand how aging is affecting your own sperm’s health. Path Fertility has released a novel test to measure the molecular health of your sperm and provide you with your true biological sperm age.

Your Sperm Age

Your sperm’s biological age (“Sperm Age”) is a measure of how your sperm is functioning at a cellular level. Aging is not the same experience for everyone and some men’s sperm age at a faster rate than others¹³ ¹⁴. Your sperm age is determined by analyzing specific modifications on your DNA called DNA methylation. DNA methylation is a common modification found on DNA where a CH3 (Methyl) molecule binds to the cytosine base of DNA. This modification changes the expression of your genes. Sperm DNA methylation is a leading mechanism for decreased fertility in older men. Aging is a multifactorial process and sperm DNA methylation has been shown to be a leading mechanism causing the adverse fertility and offspring outcomes associated with advanced paternal age¹⁵.

With aging there are steady and consistent changes in the sperm DNA methylation pattern¹³ ¹⁴. By analyzing a man’s sperm DNA methylation pattern you can very accurately identify his chronological age¹³ ¹⁴. Although largely tied to chronological age, lifestyle and behaviors can directly affect one’s Sperm Age¹⁴. So, for example, you can be 35 but have sperm that is more characteristic of a 45 year old or a 30 year old, depending on your lifestyle and behavior. Studies have shown hyper-accelerated aging in sperm is associated with regular smoking habits, cardiovascular risk, diet, as well as a BMI > 30¹⁴ ¹⁷. Additionally hyper-accelerated aging has been associated with poorer IVF outcomes and a longer time to pregnancy¹⁵.

Some behaviors that have been shown to change a man’s sperm DNA methylation patterns are:

  1. Alcohol consumption¹⁶

  2. Smoking¹⁷

  3. A low protein diet¹⁸

  4. Cannabis use²⁹

  5. Physical activity

  6. Stress²⁰

  7. Environmental chemicals such as phthalates²¹

Sperm Age testing is a better surrogate for understanding how your sperm is aging than your chronological age. The Sperm Age test is a newly developed DNA methylation based test for sperm health that looks at your true paternal age by analyzing the DNA methylation patterns of your sperm. Path Fertility is the only company providing an analysis of sperm DNA methylation and analyzing your sperm’s true biological age.

Sperm Health and General Wellness

Sperm health and aging should be routine in a general men’s health assessment! Several publications have shown a link between sperm health and overall health and lifespan ²² ²³ ²⁴ ²⁵ ²⁶. There is growing evidence that sperm health can be a surrogate for general wellness and should be measured routinely in wellness exams. Specifically there are associations with declined sperm quality and:

  1. increased risk of cancer

  2. cardiovascular disease

  3. metabolic disease

  4. autoimmune conditions

Additionally there is a clear association with sperm quality and total lifespan.

Maintaining a healthy lifestyle is crucial for optimal fertility, sperm biological aging, and overall health. Your sperm regenerates entirely every three months, with support in making lifestyle and behavioral changes you can track changes in your sperm quality and Sperm Age in just three months.

Learn more about it at the free webinar Men Matter, Thursday 9/23 at 2 pm EST.

References

  1. Hassan, M. A. M. & Killick, S. R. Effect of male age on fertility: Evidence for the decline in male fertility with increasing age. Fertil Steril. 79, 1520–1527. https://doi.org/10.1016/S0015-0282(03)00366-2 (2003).

  2. Horta, F. et al. Male ageing is negatively associated with the chance of live birth in IVF/ICSI cycles for idiopathic infertility. Hum.Reprod. 34, 2523–2532. https://doi.org/10.1093/humrep/dez223 (2019).

  3. Montgomery, S. M., Olsson, T. & Ekbom, A. Parental age, family size, and risk of multiple sclerosis. Epidemiology 15, 717–723. https://doi.org/10.1097/01.ede.0000142138.46167.69 (2004).

  4. Puleo, C. M. et al. Advancing paternal age and autism. Autism 16, 367–380. https://doi.org/10.1177/1362361311427154 (2012).12 Vol:.(1234567890)

  5. Scientific Reports | (2021) 11:3216 | https://doi.org/10.1038/s41598-020-80857-2 www.nature.com/scientificreports/

  6. Saha, S. et al. Advanced paternal age is associated with impaired neurocognitive outcomes during infancy and childhood. PLoS Med. 6, e40–e40. https://doi.org/10.1371/journal.pmed.1000040 (2009).

  7. Xie, K. et al. Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice. Proc. Natl. Acad. Sci. USA. 115, E2348–E2357. https://doi.org/10.1073/pnas.1707337115 (2018).

  8. Contreras, Z. A. et al. Parental age and childhood cancer risk: A Danish population-based registry study. Cancer Epidemiol. 49, 202–215. https://doi.org/10.1016/j.canep.2017.06.010 (2017).

  9. Sartorelli, E. M., Mazzucatto, L. F. & de Pina-Neto, J. M. Effect of paternal age on human sperm chromosomes. Fertil. Steril. 76, 1119–1123 (2001).

  10. Gratten, J. et al. Risk of psychiatric illness from advanced paternal age is not predominantly from de novo mutations. Nat. Genet. 48, 718–724. https://doi.org/10.1038/ng.3577 (2016).

  11. Reichenberg, A. et al. Advancing paternal age and autism. Arch. Gen. Psychiatry 63, 1026–1032 (2006).

  12. Snajderova, M. et al. The importance of advanced parental age in the origin of neurofibromatosis type 1. Am. J. Med. Genet. Part A 158A, 519–523. https://doi.org/10.1002/ajmg.a.34413 (2012).

  13. Jenkins TG, James ER, Alonso DF, Hoidal JR, Murphy PJ, Hotaling JM, Cairns BR, Carrell DT, Aston KI. Cigarette smoking significantly alters sperm DNA methylation patterns. Andrology. 2017 Nov;5(6):1089-1099. doi: 10.1111/andr.12416. Epub 2017 Sep 26. PMID: 28950428; PMCID: PMC5679018.

  14. Jenkins TG, Aston KI, Cairns B, Smith A, Carrell DT. Paternal germ line aging: DNA methylation age prediction from human sperm. BMC Genomics. 2018;19(1):763. Published 2018 Oct 22. doi:10.1186/s12864-018-5153-4

  15. Oluwayiose, O.A., Wu, H., Saddiki, H. et al. Sperm DNA methylation mediates the association of male age on reproductive outcomes among couples undergoing infertility treatment. Sci Rep 11, 3216 (2021).

  16. Finegersh A, Homanics GE (2014) Paternal Alcohol Exposure Reduces Alcohol Drinking and Increases Behavioral Sensitivity to Alcohol Selectively in Male Offspring. PLOS ONE 9(6): e99078. https://doi.org/10.1371/journal.pone.0099078

  17. Jenkins TG, Aston KI, Pflueger C, Cairns BR, Carrell DT. Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility. PLoS genetics. 2014;10(7):e1004458.

  18. Watkins, A. J. et al. Paternal diet programs offspring health through sperm- and seminal plasma-specific pathways in mice. Proc. Natl. Acad. Sci. 115, 10064–10069. https://doi.org/10.1073/pnas.1806333115 (2018).

  19. Murphy, S. K. et al. Cannabinoid exposure and altered DNA methylation in rat and human sperm. Epigenetics 13, 1–14. (2018).

  20. Wu, L. et al. Paternal psychological stress reprograms hepatic gluconeogenesis in offspring. Cell Metab. 23, 735–743. https://doi.org/10.1016/J.CMET.2016.01.014 (2016).

  21. Wu, H. et al. Preconception urinary phthalate concentrations and sperm DNA methylation profiles among men undergoing IVF treatment: A cross-sectional study. Hum. Reprod. 32, 2159–2169. https://doi.org/10.1093/humrep/dex283 (2017).

  22. Choy JT, Eisenberg ML. Male infertility as a window to health. Fertil Steril. 2018 Oct;110(5):810-814. doi: 10.1016/j.fertnstert.2018.08.015. PMID: 30316415.

  23. Eisenberg ML, Li S, Cullen MR, Baker LC. Increased risk of incident chronic medical conditions in infertile men: analysis of United States claims data. Fertil Steril. 2016 Mar;105(3):629-636. doi: 10.1016/j.fertnstert.2015.11.011. Epub 2015 Dec 7. PMID: 26674559.

  24. Brubaker WD, Li S, Baker LC, Eisenberg ML. Increased risk of autoimmune disorders in infertile men: analysis of US claims data. Andrology. 2018 Jan;6(1):94-98. doi: 10.1111/andr.12436. Epub 2017 Nov 27. PMID: 29179258.

  25. Eisenberg ML, Li S, Brooks JD, Cullen MR, Baker LC. Increased risk of cancer in infertile men: analysis of U.S. claims data. J Urol. 2015 May;193(5):1596-601. doi: 10.1016/j.juro.2014.11.080. Epub 2014 Nov 15. PMID: 25463997.

  26. Del Giudice F, Kasman AM, Ferro M, Sciarra A, De Berardinis E, Belladelli F, Salonia A, Eisenberg ML. Clinical correlation among male infertility and overall male health: A systematic review of the literature. Investig Clin Urol. 2020 Jul;61(4):355-371. doi: 10.4111/icu.2020.61.4.355. Epub 2020 Jun 8. PMID: 32665992; PMCID: PMC7329649.

Dr. Burns
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