A new study suggests that regular planned exercise, not just being generally active, protects against certain aspects of muscle aging [1].
Are trained muscles younger?
With age, skeletal muscles lose strength, metabolic flexibility, and mitochondrial capacity. While regular exercise slows many aspects of functional aging [2], just how deeply training affects the molecular state of old human muscle is less known. Specifically, scientists have been trying to understand whether trained older muscles retain a more youthful molecular profile and whether physical fitness changes the way that older muscles respond to exercise.
These questions are difficult to answer since old people are generally less active than young people. Therefore, a molecular difference attributed to aging might actually reflect discrepancies in physical activity. The authors of a new study from Amsterdam UMC and Maastricht University, published in Nature Aging, tried to separate the two by comparing young adults with equally active older adults. To understand whether types of activity matter, they also included a group of highly trained older people.
The cohort contained 47 people overall: 11 young adults (average age 23), 16 trained older adults (average age 68), 15 normally active older adults, and 5 physically impaired older adults. “Trained” meant having at least three planned one-hour exercise sessions per week for more than a year. Physical impairment was defined as failing to pass the Short Physical Performance Battery (SPPB), a clinical test of balance, walking speed, and chair-standing ability.
Training seems to partially protect against muscle aging
The team examined muscles both at rest and immediately after exercise (one hour of cycling), reasoning that an acute physical challenge might expose differences that are not visible at baseline. Thigh-muscle biopsies were taken before and immediately after exercise. The researchers measured gene expression, metabolites, and lipid content.
The young group took almost the same number of daily steps (10,200) as the normally active older group (9,600). Time spent on higher-intensity activity was also broadly similar. Nevertheless, the groups were clearly separated at all three molecular levels.
Older muscles showed a particularly strong reduction in the expression of genes involved in mitochondrial respiration and energy production. Metabolomics pointed in the same direction: several metabolites in the NAD+ pathway were reduced, and NAD+ is a coenzyme needed for energy metabolism and many cellular stress-response and repair reactions. The comparison suggested that mitochondrial and energy programs decline with age even for people who remain reasonably active in daily life.
Sustained, structured training, however, appears to protect against these changes. More than half of the age-related changes in gene expression – in 56% of the upregulated and 57% of the downregulated genes – were absent in trained old adults. This effect was most prominent in mitochondrial and energy-metabolism genes, whose downregulation emerged as the clearest features of muscle aging. Some of the differentially regulated genes unaffected by training were related to synaptic or cell-signaling processes, tissue maintenance, and regeneration. The paper interprets the first group of changes as “preventable” by structured training and the second as “unavoidable.”
Reaction to acute exercise
The transcriptional response to an acute bout of exercise differed in young and older adults. However, the gap was the smallest in trained older adults; their response most closely resembled that of young people, while the impaired group was the most divergent.
The authors then examined genes that rose or fell following exercise in both young and normally active older adults. These shared exercise-induced changes included upregulation of several inflammation- and cellular stress-related genes, such as IL6, IL1B, and TNF. This acute reaction to exercise is well known from previous research [3], but here, it was most pronounced in trained adults.
The authors interpret this as a sign that healthier older muscles may be better able to activate an advantageous temporary stress and repair program when challenged. However, the research does not show a causative effect, only a correlation.
An important caveat is that exercise intensity was relative – 50% of the personal maximum – meaning that it might have been objectively higher in trained older adults than even in the young cohort, and the authors acknowledge this as a possible confounder. Regular strenuous exercise could have conditioned the trained participants’ muscles to mount a stronger acute response, rather than that response being what makes them healthier.
This study might be the most detailed analysis to date of the molecular features of muscle aging and how they correlate with structured training and physical activity. While not offering proof of causality, overall, it suggests that training muscles is as important in preventing certain aspects of aging as clocking in daily steps. On the other hand, it is not a miracle cure, and geroscience should be focused on solving the part of muscle aging that appears to be “exercise-proof.”
Literature
[1] Janssens, G. E., Trętowicz, M. M., Grevendonk, L., Kotte, M., Scantlebery, A., Schomakers, B. V., … & Houtkooper, R. H. (2026). Delayed molecular aging, preservation of energy metabolism and enhanced exercise response in exercise-trained human muscle Nature Aging, 1-19.
[2] Valenzuela, P. L., Saco-Ledo, G., Morales, J. S., Gallardo-Gómez, D., Morales-Palomo, F., López-Ortiz, S., … & Lucia, A. (2023). Effects of physical exercise on physical function in older adults in residential care: a systematic review and network meta-analysis of randomised controlled trials. The lancet Healthy longevity, 4(6), e247-e256.
[3] Petersen, A. M. W., & Pedersen, B. K. (2005). The anti-inflammatory effect of exercise. Journal of applied physiology, 98(4), 1154-1162.
View the article at lifespan.io
