10 Longevity Interventions with Major Sex-Specific Differences

If Adam had taken the first bite of that apple before Eve, the story of humanity might have unfolded just the same. That’s for what happened outside their bodies. Inside, though, the story would look quite different.

An apple contains carbohydrates, fibers, and natural sugars—all of which are metabolized in subtly different ways by men and women. The same bite, the same calories, yet not quite the same biological consequences.

These biological differences between the sexes have long fascinated scientists, and for good reason. They shape everything from fat distribution and muscle recovery to disease risk and drug response.

These nuances also influence survival, or in twenty-first-century terms, our longevity.

Sometimes nature gives one sex an edge in growth and development, but another in resilience to stress. The trade-offs are intricate, and they play out in nearly every longevity trend we observe today.

Historically, women have unfortunately been underrepresented in clinical research, leaving many longevity truths biased toward male physiology.

Yet today, we’ll dig through what’s known so far to understand how ten of the most popular longevity interventions act differently in men and women. 

1- Intermittent Fasting

Intermittent fasting is an eating regimen that cycles between periods of eating and periods of little or no food intake. It triggers cellular repair processes and improves metabolic markers through activation of autophagy, the cell’s housekeeping mechanism for clearing damaged parts. But this intervention doesn’t show similar results for women and men.

In rodent studies, female mice exposed to intermittent fasting showed suppressed estrogen, disrupted menstrual cycles, and reduced fertility, whereas male mice maintained stable reproductive function under the same regimen [1]. 

In short-term human trials, young men improved insulin sensitivity after a few weeks of fasting, while women experienced a relative worsening of glucose control and menstrual irregularities [2]. 

The root of these discrepancies lies in evolution: women’s bodies interpret energy scarcity as a reproductive threat, triggering hormonal compensations to protect fertility. Men’s physiology is less constrained by short-term energy shifts, so their metabolic balance holds steadier under fasting stress [3].

Takeaway: Men often tolerate longer fasts with clearer metabolic benefit. Women, especially while still of reproductive age, should favor gentler fasting windows and monitor menstrual, hormonal, and blood sugar signals rather than pushing aggressive fasts.

2- Exercise

Regular exercise, from brisk walking to weightlifting, is perhaps the most powerful lifestyle medicine for longevity. Interestingly, though, the two sexes can respond somewhat differently to the same workout routine. Women often gain an edge in endurance and longevity benefits at lower exercise doses compared to men.

One study of over 412,000 adults found that women achieved a 24% reduction in all-cause mortality with regular physical activity, versus 15% in men. Women reached this benefit with about half the exercise volume required for men, likely due to differences in body composition and cardiovascular efficiency [4].

Part of this is physiology: women tend to have more slow-twitch muscle fibers and denser capillaries, aiding blood flow and efficient fuel use during exercise [5]. These traits mean a woman’s body can adapt and improve cardiovascular health with gentler activity. 

Men, on the other hand, build muscle mass more easily and increase strength faster thanks to testosterone. This gives them an edge over women when it comes to maintaining muscle with age [6].

Takeaway: Women gain longevity efficiently from moderate exercise but must prioritize strength training, while men may need greater endurance volume for equivalent longevity gains.

3- Saunas

Frequent sauna bathing has emerged as a healthful habit linked to longevity. Studies in Finland found that regular sauna-goers have lower risks of heart disease, dementia, and even death from any cause [7]. Notably, however, most of these studies were conducted on men only. 

Where we have more insight into the differences between men and women is in heat tolerance and adaptation. In one study, males achieved full heat-adaptation (lower heart rate and cooler core temperature during heat exposure) in under a week of daily sessions, whereas females took closer to two weeks. Women’s higher average body fat, which conserves heat, and hormonal fluctuations also mean that an intense sauna might feel more taxing initially [8]. However, after a gradual ramp-up, women reap the same cardiovascular rewards as men from sauna therapy [9]. 

Takeaway: Men might tolerate longer or hotter sessions right off the bat. On the other hand, women may want to start with shorter, moderate-heat sessions and increase duration slowly as their heat tolerance builds. And of course, more studies are needed on health outcomes with sauna bathing for women.

4- Omega-3 Fatty Acids

Omega-3 fatty acids, especially EPA and DHA found in fish oil,  are well-known longevity supplements. They are anti-inflammatory and support heart and brain health. But research hints at some sex-specific nuances in how omega-3s work in the body. 

Notably, women might derive more brain benefit from omega-3 intake than men. Large analyses of omega-3 trials have observed that women taking fish oil showed improvements in cognitive measures, whereas men often saw little change [10]. In fact, lifelong high omega-3 consumption has been linked to lower risk of dementia, with recent findings that women with Alzheimer’s disease tend to have strikingly low omega-3 levels [11]. This pattern is not seen in male Alzheimer’s patients. 

When it comes to heart health, some data suggest men using omega-3s see a bit more reduction in certain cardiac risks, possibly because their baseline risk is higher [12].

Takeaway: For women, omega-3 intake is especially beneficial for preserving cognitive health with age. Men also benefit from omega-3s, but the evidence doesn’t single them out as dramatically. 

5- Vitamin D

Vitamin D, aka the “sunshine vitamin,” supports bone integrity, muscle function, and immune health. While many adults have suboptimal vitamin D levels, deficiency patterns and the consequences can differ by sex. 

Women, particularly at older ages, are more prone to severe vitamin D deficiency than men [13]. This is partly because women often have less outdoor sun exposure and because their body fat can sequester fat-soluble vitamins, making blood levels lower [14]. Postmenopausal women are at particular risk, as without estrogen’s bone-protective effect, low vitamin D quickly translates to bone loss and fracture risk [15]. 

Perhaps for these reasons, having very low vitamin D seems even more dangerous for women’s survival. One study reported that the increase in mortality risk associated with vitamin D deficiency was greater in women than in men [16].

Takeaway: Men and especially women should treat vitamin D as a priority nutrient throughout life, not just for bone health but for overall vitality into old age.

6- Creatine 

Creatine is a compound best known for boosting muscle energy and strength, and lately even for enhancing brain health. Creatine’s effects can depend on sex too, largely due to differences in baseline levels. 

Women start off with 70-80% lower creatine reserves in muscles than men [17]. This gap is mostly because men naturally have more muscle mass. For women, however, this lower reservoir surprisingly poses some good news. It means supplementation can create a more pronounced change. 

Research indeed finds that women often experience greater cognitive boosts from creatine than men do. A meta-analysis of trials noted that creatine supplements led to improved memory and attention mainly in females, whereas the benefit in males was smaller [18]. 

In terms of muscle aging, both men and women build lean mass a bit better with creatine, but men see a larger absolute gain since they build muscle faster in general. Women still get relatively stronger and may see improvements in muscle endurance and bone density from creatine, which can aid longevity by preventing falls [19]. 

Takeaway: Creatine isn’t just for big beefy boys in the weight room. In fact, women stand to gain a lot from it. If you’re female and eat little meat or feel mentally foggy at times, creatine could noticeably improve your energy and cognition while also supporting your muscles.

7- NAD+ Boosters 

NAD+ is a vital molecule found in all our cells, involved in energy production and DNA repair. Yet, levels of NAD+ decline with age [20]. Accordingly, supplements that elevate NAD+, like NR and NMN, are being explored as longevity interventions. However, male and female bodies may not respond identically to NAD+ elevation. 

In animal research, NMN extended lifespan in females but mainly improved metabolism only in males [21]. Human studies reveal a subtle parallel. Women show a higher NAD+/NADH redox ratio, meaning their cells maintain a more efficient energy balance [22]. This may explain why female animals show stronger longevity effects from NAD+ restoration.

Takeaway: NAD+ boosters may hold promise for all longevity enthusiasts, but women might find more major benefits in lifespan extension than men. 

8- Rapamycin

Rapamycin is an immunosuppressant drug that, at low periodic doses, has shown significant lifespan extension in lab animals. It inhibits mTOR, a cellular growth pathway, thereby slowing age-related decline and reducing cancer incidence [23]. 

Experiments across various mouse strains have found that rapamycin increases longevity in both sexes, but consistently more so in females. In general, female mice get about a 26% lifespan extension from rapamycin, whereas males might get around 23% [24]. 

But why the gap? A few reasons are proposed. Female aging in mice is heavily influenced by cancer, and rapamycin is very effective at suppressing tumor growth [25]. So it disproportionately supports females by keeping cancer at bay. 

Takeaway: Rapamycin is one of the most famous longevity interventions, but women could stand to gain more from its life-extending effects if future human studies mirror the animal findings.

9- Metformin

Metformin is a decades-old oral drug for type 2 diabetes that’s garnered attention as a repurposed drug for longevity. It works by improving insulin sensitivity and activating AMPK, an energy-sensing pathway, thereby mimicking some effects of calorie restriction [26]. 

In some experiments, lifelong metformin treatment significantly extended lifespan in female mice but actually shortened lifespan in male mice [27]. Why would the same drug help females and harm males? A leading hypothesis involves energy and growth signaling. Metformin suppresses the aforementioned mTOR pathway. So, like rapamycin, it also helps female mice avoid cancer.

Takeaway: Metformin’s effects depend on who’s taking it. If you’re a woman (especially with insulin resistance or risk of diabetes), metformin could improve metabolic health and potentially longevity, as it targets mechanisms that are relevant to female aging. 

10- GLP-1 Receptor Agonists (Ozempic and Friends)

GLP-1 receptor agonists, such as semaglutide and liraglutide, have taken the world by storm for their success in managing type 2 diabetes and obesity. They imitate the GLP-1 hormone that releases insulin, increases satiety, and reduces appetite, leading patients to eat less and steadily shed fat [28]. Given obesity’s toll on longevity, GLP-1 drugs are being considered pro-longevity interventions. However (you get the drill now), clinical data reveals a sex difference.

In weight-loss trials, females consistently see a slightly greater percentage drop in body weight compared to males on the same drug. For instance, in a trial of semaglutide for obesity-related heart failure, women lost about 9.6% of their body weight on average, whereas men lost around 7.2% [29]. Part of the explanation lies in women often having higher blood concentrations of the drug for a given dose. Hormonal differences may contribute as well, as GLP-1 pathways interact with estrogen and other signals involved in hunger and fullness. 

Congruently, however, when it comes to side effects like nausea, women report them more frequently, indicative of a more intense physiological response to these drugs [30]. 

Takeaway: If indicated, these drugs are a powerful tool for improving metabolic health. Both sexes see remarkable weight loss, with women generally losing more weight but experiencing more side effects.  

Bonus Intervention: Marriage

Marriage is certainly an intervention—and an exceptionally influential one in that it’s capable of shaping not only your social life but how long you live. And guess what? The effects are far from equally distributed between the sexes.

Men, it turns out, draw a bigger longevity dividend from tying the knot. A computational analysis found that men gain roughly 8.5 months of life through marriage, whereas women actually lose about 6 months once economic and behavioral dynamics are factored in [31].

Why the difference? Men likely benefit more from the health monitoring, social support, and routine that marriage brings, while women often take on more emotional and caretaking burdens, which can offset potential benefits for themselves. 

Modern evidence extends beyond lifespan to biological age. Using U.S. NHANES data, researchers found that never-married men had a 2.45-fold higher risk of accelerated biological aging compared to their married peers, whereas women who were never married actually showed a reduced risk of age acceleration [32]. In short, marriage seems to slow biological aging for men but not necessarily for women.

Takeaway: Marriage might be longevity medicine, but mostly for men. Sorry, ladies. You win some and you lose some.

References:

[1] Kumar, S., & Kaur, G. (2013). Intermittent Fasting Dietary Restriction Regimen Negatively Influences Reproduction in Young Rats: A Study of Hypothalamo-Hypophysial-Gonadal Axis. PLoS ONE, 8(1), e52416. https://doi.org/10.1371/journal.pone.0052416

[2] Heilbronn, L. K., Civitarese, A. E., Bogacka, I., Smith, S. R., Hulver, M., & Ravussin, E. (2005). Glucose Tolerance and Skeletal Muscle Gene Expression in Response to Alternate Day Fasting. Obesity Research, 13(3), 574–581. https://doi.org/10.1038/oby.2005.61

[3] Areta, J. L. (2023). Physical performance during energy deficiency in humans: An evolutionary perspective. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 284, 111473. https://doi.org/10.1016/j.cbpa.2023.111473

[4] Ji, H., Gulati, M., Tzu Yu Huang, Kwan, A. C., Ouyang, D., Ebinger, J. E., Casaletto, K., Moreau, K. L., Hicham Skali, & Cheng, S. (2024). Sex Differences in Association of Physical Activity With All-Cause and Cardiovascular Mortality. Journal of the American College of Cardiology, 83(8), 783–793. https://doi.org/10.1016/j.jacc.2023.12.019

[5] Nuzzo, J. L. (2023). Sex differences in skeletal muscle fiber types: A meta-analysis. Clinical Anatomy (New York, N.Y.), 37(1). https://doi.org/10.1002/ca.24091

[6] Roberts, B. M., Nuckols, G., & Krieger, J. W. (2020). Sex Differences in Resistance Training. Journal of Strength and Conditioning Research, 34(5), 1448–1460. https://doi.org/10.1519/jsc.0000000000003521

[7] Tanjaniina Laukkanen, Khan, H., Zaccardi, F., & Laukkanen, J. A. (2015). Association Between Sauna Bathing and Fatal Cardiovascular and All-Cause Mortality Events. JAMA Internal Medicine, 175(4), 542–548. https://doi.org/10.1001/jamainternmed.2014.8187

[8] Wickham, K. A., Wallace, P. J., & Cheung, S. S. (2020). Sex differences in the physiological adaptations to heat acclimation: a state-of-the-art review. European Journal of Applied Physiology, 121(2), 353–367. https://doi.org/10.1007/s00421-020-04550-y

[9] Laukkanen, T., Kunutsor, S. K., Khan, H., Willeit, P., Zaccardi, F., & Laukkanen, J. A. (2018). Sauna bathing is associated with reduced cardiovascular mortality and improves risk prediction in men and women: a prospective cohort study. BMC Medicine, 16(1). https://doi.org/10.1186/s12916-018-1198-0

[10] Welty, F. K., Daher, R., & Mahdi Garelnabi. (2024). Fish and Omega-3 Fatty Acids: Sex and Racial Differences in Cardiovascular Outcomes and Cognitive Function. Arteriosclerosis, Thrombosis, and Vascular Biology, 44(1), 89–107. https://doi.org/10.1161/atvbaha.122.318125

[11] Wretlind, A., Xu, J., Chen, W., Velayudhan, L., Ashton, N. J., Zetterberg, H., Proitsi, P., & Legido‐Quigley, C. (2025). Lipid profiling reveals unsaturated lipid reduction in women with Alzheimer’s disease. Alzheimer’s & Dementia, 21(8). https://doi.org/10.1002/alz.70512

[12] Welty, F. K., Daher, R., & Mahdi Garelnabi. (2024). Fish and Omega-3 Fatty Acids: Sex and Racial Differences in Cardiovascular Outcomes and Cognitive Function. Arteriosclerosis, Thrombosis, and Vascular Biology, 44(1), 89–107. https://doi.org/10.1161/atvbaha.122.318125

[13] Kader, S., Comaklı, H., & Tekindal, M. (2019). Evaluation of Serum Vitamin D Levels according to Gender and Age at Karapınar City: A Follow-Up Study from Turkey. Dubai Medical Journal, 2(4), 141–145. https://doi.org/10.1159/000503899

[14] Khadilkar, S. S. (2013). The Emerging Role of Vitamin D3 in Women’s Health. The Journal of Obstetrics and Gynecology of India, 63(3), 147–150. https://doi.org/10.1007/s13224-013-0420-4

[15] Mei, Z., Hong, H.-C., Zeng, Y., & Li, D. (2023). The role of vitamin D in menopausal women’s health. Frontiers in Physiology, 14. https://doi.org/10.3389/fphys.2023.1211896

[16] Eaton, C. B., Young, A., Allison, M. A., Robinson, J., Martin, L. W., Kuller, L. H., Johnson, K. C., Curb, J. D., Van Horn, L., McTiernan, A., Liu, S., & Manson, J. E. (2011). Prospective association of vitamin D concentrations with mortality in postmenopausal women: results from the Women’s Health Initiative (WHI). The American Journal of Clinical Nutrition, 94(6), 1471–1478. https://doi.org/10.3945/ajcn.111.017715

[17] Smith-Ryan, A. E., Cabre, H. E., Eckerson, J. M., & Candow, D. G. (2021). Creatine Supplementation in Women’s Health: A Lifespan Perspective. Nutrients, 13(3), 877. https://doi.org/10.3390/nu13030877

[18] Xu, C., Bi, S., Zhang, W., & Luo, L. (2024). The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis. Frontiers in Nutrition, 11. https://doi.org/10.3389/fnut.2024.1424972

[19] Vandenberghe, K., Goris, M., Van Hecke, P., Van Leemputte, M., Vangerven, L., & Hespel, P. (1997). Long-term creatine intake is beneficial to muscle performance during resistance training. Journal of Applied Physiology, 83(6), 2055–2063. https://doi.org/10.1152/jappl.1997.83.6.2055

[20] McReynolds, M. R., Chellappa, K., & Baur, J. A. (2020). Age-related NAD+ decline. Experimental Gerontology, 134, 110888. https://doi.org/10.1016/j.exger.2020.110888

[21] Kane, A. E., Chellappa, K., Schultz, M. B., Arnold, M., Li, J., Amorim, J., Diener, C., Zhu, D., Mitchell, S. J., Griffin, P., Tian, X., Petty, C., Conway, R., Walsh, K., Shelerud, L., Duesing, C., Mueller, A., Li, K., McNamara, M., & Shima, R. T. (2024). Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner. BioRxiv: The Preprint Server for Biology, 2024.06.21.599604. https://doi.org/10.1101/2024.06.21.599604

[22] Schwarzmann, L., Pliquett, R. U., Simm, A., & Bartling, B. (2021). Sex-related differences in human plasma NAD+/NADH levels depend on age. Bioscience Reports, 41(1). https://doi.org/10.1042/bsr20200340

[23] Lee, D. J. W., Ajla Hodzic Kuerec, & Maier, A. B. (2024). Targeting ageing with rapamycin and its derivatives in humans: a systematic review. The Lancet Healthy Longevity, 5(2), e152–e162. https://doi.org/10.1016/s2666-7568(23)00258-1

[24] Miller, R. A., Harrison, D. E., Astle, C. M., Fernandez, E., Flurkey, K., Han, M., Javors, M. A., Li, X., Nadon, N. L., Nelson, J. F., Pletcher, S., Salmon, A. B., Sharp, Z. D., Van Roekel, S., Winkleman, L., & Strong, R. (2014). Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. Aging Cell, 13(3), 468–477. https://doi.org/10.1111/acel.12194

[25] Bai, H., Liu, X., Lin, M., Meng, Y., Tang, R., Guo, Y., Li, N., Clarke, M. F., & Cai, S. (2024). Progressive senescence programs induce intrinsic vulnerability to aging-related female breast cancer. Nature Communications, 15(1). https://doi.org/10.1038/s41467-024-49106-2

[26] Soukas, A. A., Hao, H., & Wu, L. (2019). Metformin as Anti-Aging Therapy: Is It for Everyone? Trends in Endocrinology and Metabolism: TEM, 30(10), 745–755. https://doi.org/10.1016/j.tem.2019.07.015

[27] Anisimov, V. N., Piskunova, T. S., Popovich, I. G., Zabezhinski, M. A., Tyndyk, M. L., Egormin, P. A., Yurova, M. N., Rosenfeld, S. V., Semenchenko, A. V., Kovalenko, I. G., Poroshina, T. E., & Berstein, L. M. (2010). Gender differences in metformin effect on aging, life span and spontaneous tumorigenesis in 129/Sv mice. Aging, 2(12), 945–958. https://doi.org/10.18632/aging.100245

[28] Zheng, Z., Zong, Y., Ma, Y., Tian, Y., Pang, Y., Zhang, C., & Gao, J. (2024). Glucagon-like peptide-1 receptor: Mechanisms and Advances in Therapy. Signal Transduction and Targeted Therapy, 9(1), 1–29. https://doi.org/10.1038/s41392-024-01931-z

[29] Verma, S., Butler, J., Borlaug, B. A., Davies, M., Kitzman, D. W., Shah, S. J., Petrie, M. C., Barros, E., Rönnbäck, C., Lene Sommer Vestergaard, Schou, M., Ezekowitz, J. A., Sharma, K., Patel, S., Chinnakondepalli, K. M., & Kosiborod, M. N. (2024). Efficacy of Semaglutide by Sex in Obesity-Related Heart Failure With Preserved Ejection Fraction. Journal of the American College of Cardiology. https://doi.org/10.1016/j.jacc.2024.06.001

[30] Rentzeperi, E., Pegiou, S., Koufakis, T., Grammatiki, M., & Kotsa, K. (2022). Sex Differences in Response to Treatment with Glucagon-like Peptide 1 Receptor Agonists: Opportunities for a Tailored Approach to Diabetes and Obesity Care. Journal of Personalized Medicine, 12(3), 454. https://doi.org/10.3390/jpm12030454

[31] Schünemann, J., Strulik, H., & Trimborn, T. (2020). The marriage gap: Optimal aging and death in partnerships. Review of Economic Dynamics, 36, 158–176. https://doi.org/10.1016/j.red.2019.09.004