Key Takeaways
- A study of 682 adults aged 65 and older found that greater physical activity was generally associated with better muscle mass and physical function.
- Among women with the ACTN3 XX genotype, however, physical activity and chair-stand performance showed an unexpected U-shaped relationship.
- Researchers identified an exploratory turning point of about 441 MET-minutes per week. Above that point, greater self-reported activity was associated with slower chair-stand performance.
- The study was cross-sectional and cannot show that exercise caused poorer performance.
- The 441 MET-minute figure is not a recommended exercise limit.
- The findings do not support exercising less or using ACTN3 genetic testing to prescribe exercise.
Researchers are studying whether ACTN3 variants influence the relationship between physical activity and muscle function in older women.
Exercise helps preserve strength, mobility, and independence with age. But people do not respond identically to physical activity, and genetics may contribute to some of those differences.
A 2026 study published in Scientific Reports examined whether a common variant of the ACTN3 gene influences the relationship between physical activity and muscle function in older adults (Hsu et al., 2026).
Most participants showed the expected pattern: greater activity was associated with better muscle-related outcomes. But among women with two copies of the ACTN3 577X variant—the XX genotype—researchers found a more complicated relationship between activity and chair-stand performance.
The finding is intriguing, but it does not show that women with this genotype should exercise less.
What Is ACTN3?
ACTN3 provides instructions for producing alpha-actinin-3, a protein expressed in fast-twitch, or type II, skeletal muscle fibers. These fibers are important for rapid, forceful movements and muscle power.
The common ACTN3 R577X variant can prevent the production of functional alpha-actinin-3. People with the RR or RX genotype produce the protein, while people with the XX genotype do not.
Alpha-actinin-3 deficiency is not a muscle disease. In the new study, 16.9% of participants had the XX genotype (Hsu et al., 2026).
ACTN3 has been extensively studied in athletic performance, but its importance for physical activity and muscle function during aging remains uncertain.
What Did the Study Examine?
Hsu and colleagues studied 682 community-dwelling adults aged 65 and older who attended annual health examinations between March 2021 and October 2024.
Participants had an average age of about 73 years, 41.8% were men, and 17.8% met the criteria for sarcopenia.
Researchers assessed:
- Appendicular skeletal muscle mass using dual-energy X-ray absorptiometry
- Grip strength
- Usual walking speed
- Five-repetition chair-stand time
- Physical activity
- ACTN3 R577X genotype
Physical activity was estimated using the Chinese version of the International Physical Activity Questionnaire, which asked participants about activity during the previous seven days.
Researchers converted the reported activity into metabolic equivalent minutes per week, or MET-minutes. Vigorous activity was assigned eight METs, moderate activity four METs, and walking 3.3 METs.
MET-minutes combine estimated activity intensity and duration. For example, 150 minutes of activity assigned four METs equals 600 MET-minutes.
Physical Activity Was Generally Linked to Better Muscle Function
Across the study population, greater physical activity was associated with greater skeletal muscle mass and better physical function.
In men, higher activity was associated with:
- A lower likelihood of sarcopenia
- Greater skeletal muscle mass
- Faster walking speed
- Faster chair-stand performance
In women, higher activity was associated with greater skeletal muscle mass, stronger grip, faster walking speed, and faster chair-stand performance.
The pattern changed when researchers considered ACTN3 genotype.
Among men and women carrying the RR or RX genotype, each additional 500 MET-minutes of weekly activity was associated with faster walking and chair-stand performance.
Those associations were not observed in participants with the XX genotype.
In women, the interaction between ACTN3 genotype and physical activity was statistically significant for both walking speed and chair-stand performance. When researchers tested for nonlinear relationships, however, only chair-stand performance showed a statistically significant U-shaped pattern.
The 441 MET-Minute Finding
Among women with the ACTN3 XX genotype, researchers identified an inflection point at approximately 441 MET-minutes per week.
Above that point, every additional 500 MET-minutes of weekly activity was associated with a 4.19-second longer time to complete five chair stands. The 95% confidence interval ranged from about 0.98 to 7.40 seconds (Hsu et al., 2026).
Because a longer chair-stand time indicates poorer performance, greater activity above this point was associated with worse chair-stand performance in this subgroup.
No statistically significant association was found below 441 MET-minutes.
Walking speed showed a similar U-shaped trend in women with the XX genotype, but that nonlinear relationship was not statistically significant.
Importantly, ACTN3 genotype itself was not significantly associated with muscle mass, grip strength, walking speed, chair-stand time, or sarcopenia after adjustment for age and body mass index.
The unusual result therefore involved the relationship between activity and one physical-performance measure in a specific subgroup—not evidence that the XX genotype generally causes poor muscle function (Hsu et al., 2026).
Why 441 MET-Minutes Is Not an Exercise Limit
The 441 MET-minute figure came from statistical modeling of one observational dataset. The researchers described it as exploratory and said it requires external validation.
The study was also cross-sectional. Physical activity and muscle function were assessed during the same general period, so researchers cannot determine whether greater activity led to poorer chair-stand performance.
The reverse is also possible: differences in health or physical function could influence how much activity people perform or report.
Physical activity was self-reported rather than continuously measured with wearable devices, creating additional uncertainty from recall and reporting errors.
The questionnaire also did not distinguish between aerobic and resistance exercise. Walking, physically demanding work, endurance exercise, and progressive strength training can have different physiological effects despite generating similar estimated MET totals.
For these reasons, 441 MET-minutes should not be treated as a safety threshold or exercise ceiling.
Previous ACTN3 Studies Have Produced Mixed Results
Earlier research does not show a consistent disadvantage for older women with the XX genotype.
A 2013 study examined 139 older Caucasian women before and after 12 weeks of high-speed power training. The program used upper- and lower-body exercises at intensities progressing from 40% to 75% of one-repetition maximum.
ACTN3 genotype interacted significantly with training for 10-meter walking-speed performance, with RR and RX carriers showing a more favorable response than women with the XX genotype. ACTN3 genotype did not significantly influence the get-up-and-go mobility test (Pereira et al., 2013).
Unlike the new observational study, this research used a defined training program and measured changes over time.
A 2020 study of 300 physically active Spanish women older than 60 produced a different result. Participants took part in a two-year supervised program combining endurance, resistance, balance, mobility, and coordination exercises.
Women with the XX genotype recorded better chair-stand results after the program than the other genotype groups, while X-allele carriers also showed improvements in selected measures of arm strength (Romero-Blanco et al., 2020).
The study lacked a non-exercising control group, however, so it cannot establish that exercise caused all the observed changes.
Together, these studies show why ACTN3 cannot yet reliably predict how an individual older woman will respond to exercise.
Age and Sex May Also Matter
A separate study of 1,463 Chinese adults aged 70 to 87 found age- and sex-specific associations between ACTN3 and physical function.
Among men aged 70 to 79, the 577X allele was associated with slower walking, weaker grip strength, and slower timed up-and-go performance.
Among women aged 70 to 79, it was associated with a laboratory-based frailty index.
These associations were not detected among participants aged 80 to 87 (Ma et al., 2018).
The findings add to evidence that any effect of ACTN3 on physical function is likely influenced by age, sex, population characteristics, and other factors rather than genotype alone.
What Could Explain the Finding?
One possible explanation involves fast-twitch muscle fibers.
Alpha-actinin-3 is expressed in type II muscle fibers, which contribute to strength and power. These fibers are also particularly affected by aging. Because people with the XX genotype do not produce alpha-actinin-3, their muscles may respond differently to some types or amounts of physical activity.
The study authors also discussed possible effects of sex-related biology, including changes associated with reduced estrogen after menopause.
But these mechanisms were not directly tested.
The researchers did not measure muscle-fiber characteristics with biopsies, objectively track training loads or recovery, distinguish resistance exercise from aerobic exercise, or randomly assign participants to exercise programs.
The observed relationship could therefore reflect a genuine gene-activity interaction, unmeasured differences between participants, statistical uncertainty, or a combination of factors.
Why the Subgroup Result Needs Confirmation
Although the full study included 682 people, only 16.9% had the XX genotype. Dividing that group further by sex reduces the number of participants supporting the key finding.
Results from relatively small subgroups can be less stable and require replication before they should influence clinical recommendations.
Larger prospective studies could use wearable activity monitors, distinguish specific types of exercise, and follow participants over time.
Randomized trials would provide stronger evidence by comparing defined aerobic, resistance, and combined exercise programs among people with different ACTN3 genotypes.
Should Older Women Change How They Exercise?
Not based on this study.
The World Health Organization recommends that adults aged 65 and older perform 150 to 300 minutes of moderate-intensity aerobic activity per week, 75 to 150 minutes of vigorous activity, or an equivalent combination (World Health Organization, 2020).
Older adults should also perform muscle-strengthening activities involving the major muscle groups on at least two days per week. Multicomponent physical activity emphasizing functional balance and strength is recommended on at least three days per week to help maintain function and prevent falls (World Health Organization, 2020).
The new ACTN3 study does not overturn those recommendations.
Instead, it raises a question for future research: whether factors such as sex, genetics, exercise type, intensity, and recovery could eventually help researchers better understand individual responses to exercise.
Older adults experiencing worsening strength, unusual fatigue, pain, falls, or declining mobility should discuss those changes with a healthcare professional rather than reducing physical activity based on an ACTN3 result.
Should You Get an ACTN3 Genetic Test?
There is currently no evidence from this study that routine ACTN3 testing improves exercise safety or determines an ideal exercise program.
Physical performance depends on many genetic and non-genetic factors, including age, health, training history, nutrition, medications, sleep, injuries, exercise type, and recovery.
Commercial genetic tests sometimes describe ACTN3 as a “sports gene” or “power gene,” but those labels can make its influence sound more deterministic than the evidence supports.
The new study did not test whether knowing a person’s ACTN3 genotype improves exercise outcomes or prevents injury.
For now, direct measures such as strength, walking speed, balance, chair-stand performance, symptoms, recovery, and changes over time provide more actionable information for tailoring exercise.
Frequently Asked Questions
Does the ACTN3 XX genotype cause muscle weakness?
No. Alpha-actinin-3 deficiency is common and is not considered a muscle disease.
ACTN3 variants have been associated with differences in some measures of strength, power, mobility, and frailty, but findings vary across studies and populations.
Does This Study Show That Too Much Exercise Is Harmful for Some Women?
No.
It found an association between greater self-reported physical activity and slower chair-stand performance above an exploratory statistical turning point in older women with the XX genotype.
Because the study was cross-sectional, it cannot show that greater activity caused poorer performance.
Should Women With the XX Genotype Stay Below 441 MET-Minutes per Week?
No.
The researchers described 441 MET-minutes as an exploratory finding requiring further validation. It is not a clinical exercise limit.
Is 441 MET-Minutes the Same as 441 Minutes of Exercise?
No.
MET-minutes combine estimated intensity and duration. For example, 100 minutes of activity assigned four METs equals 400 MET-minutes.
Can Genetic Testing Identify the ACTN3 XX Genotype?
Yes. Genetic testing can identify ACTN3 R577X status. However, current evidence does not show that routine ACTN3 testing can reliably determine the best exercise program for an individual.
Final Thoughts
A 2026 study found that older women with the ACTN3 XX genotype showed an unusual U-shaped relationship between self-reported physical activity and chair-stand performance.
The estimated turning point—441 MET-minutes per week—is an exploratory statistical finding, not an exercise limit.
Previous ACTN3 studies have produced mixed results, and the new study cannot establish cause and effect. More rigorous research is needed before ACTN3 genotype can be used to personalize exercise recommendations.
For now, the broader evidence continues to support regular aerobic, strength, and balance activity for older adults, adjusted to individual health, ability, symptoms, and recovery.
References
Hsu, H.-C., Fang, W.-H., Lee, M.-C., Chen, W.-T., Chen, Y.-H., Lin, H.-T., Wang, C.-C., Lin, S.-B., Chen, C.-J., Chen, M.-J., & Su, S.-L. (2026). Sex-specific physical activity thresholds influencing muscle function in older adults with XX genotype of ACTN3 R577X. Scientific Reports, 16, 27560. https://doi.org/10.1038/s41598-026-57340-5
Ma, T., Lu, D., Zhu, Y.-S., Chu, X.-F., Wang, Y., Shi, G.-P., Wang, Z.-D., Yu, L., Jiang, X.-Y., & Wang, X.-F. (2018). ACTN3 genotype and physical function and frailty in an elderly Chinese population: The Rugao Longevity and Ageing Study. Age and Ageing, 47(3), 416–422. https://doi.org/10.1093/ageing/afy007
Pereira, A., Costa, A. M., Leitão, J. C., Monteiro, A. M., Izquierdo, M., Silva, A. J., Bastos, E., & Marques, M. C. (2013). The influence of ACE I/D and ACTN3 R577X polymorphisms on lower-extremity function in older women in response to high-speed power training. BMC Geriatrics, 13, 131. https://doi.org/10.1186/1471-2318-13-131
Romero-Blanco, C., Artiga-González, M. J., Gómez-Cabello, A., Vila-Maldonado, S., Casajús, J. A., Ara, I., & Aznar, S. (2020). Strength and endurance training in older women in relation to ACTN3 R577X and ACE I/D polymorphisms. International Journal of Environmental Research and Public Health, 17(4), 1236. https://doi.org/10.3390/ijerph17041236
World Health Organization. (2020). WHO guidelines on physical activity and sedentary behaviour. https://www.who.int/publications/i/item/9789240015128
