Intermuscular adipose tissue in healthy human aging—effects of exercise training and implications to metabolic health

Q: What does this research mean for the field?

Intermuscular adipose tissue accumulates in healthy older adults and is associated with reduced insulin sensitivity, but exercise training reduces IMAT in young adults without reducing it in older adults. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Andrew M. Alexander; Lucy M. Fitzgibbons; Hawley Kunz; Zinnarky K Ortiz Correa; K. Sreekumaran Nair; John D. Port; Ian R. Lanza

doi:10.1152/japplphysiol.00719.2025

October 20, 2025Journal of Applied PhysiologyOpen Access

Intermuscular adipose tissue in healthy human aging—effects of exercise training and implications to metabolic health

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Why the study?

Does 12 weeks of exercise training reduce lower leg intermuscular adipose tissue (IMAT) and improve insulin sensitivity in healthy young and older adults?

Key Points

To examine intermuscular adipose tissue (IMAT) accumulation during healthy human aging, evaluate its link to metabolic phenotypes, and determine if exercise training reverses IMAT accumulation.
Analyzed body composition via DEXA, lower leg tissue compartments via MRI segmentation, muscle oxidative capacity (ATPmax) via 31P-MRS, and insulin sensitivity via hyperinsulinemic-euglycemic clamp in young and older adults.
Evaluated a subset of 37 participants before and after completing a 12-week exercise training program.
Older adults exhibited significantly lower leg skeletal muscle volume (P=0.02, approximately 15% lower) and higher IMAT content (P<0.001) than young adults, while leg subcutaneous adipose tissue was similar.
IMAT was negatively associated with skeletal muscle oxidative capacity in the combined cohort and negatively associated with glucose infusion rate during hyperinsulinemic clamp in older adults.
Following 12 weeks of exercise training, lower leg IMAT decreased in young adults but not in older adults, while peripheral insulin sensitivity significantly increased in both cohorts.

Structured PICO

Does 12 weeks of exercise training reduce lower leg intermuscular adipose tissue (IMAT) and improve insulin sensitivity in healthy young and older adults?

P

Population

51 healthy adults, comprising 29 young adults (mean age 25 ± 4 years, 12 female, 17 male) and 22 older adults (mean age 76 ± 5 years, 14 female, 8 male). Participants were generally healthy; excluded for diagnosed diabetes, cardiovascular or pulmonary disease, uncontrolled hypothyroidism, chronic inflammatory disease, cancer, or highly physically active status (>30 mins twice/week).

I

Intervention

12 weeks of supervised exercise training, consisting of either high-intensity aerobic interval training (HIIT; 4 bouts of 4 min intervals at >90% V̇O2peak, 5 times/week) or resistance training (RT; large muscle groups, 4 days/week). Completed by a subset of 37 participants (21 young, 16 older).

C

Comparator

Baseline (pre-exercise) measurements, and comparison between young and older adult cohorts.

O

Outcome

Lower leg intermuscular adipose tissue (IMAT) volume measured by MRI, and peripheral insulin sensitivity measured by steady-state glucose infusion rate (GIR) during a 2-stage hyperinsulinemic-euglycemic clamp.surrogate

Lower leg intermuscular adipose tissue accumulates with healthy aging and correlates with reduced insulin sensitivity, but while exercise reduces IMAT in young adults, older adults appear refractory to this specific IMAT reduction despite overall metabolic benefits.

Limitations

Lower leg measurements may not accurately represent other anatomical locations such as thigh musculature
Limited sample size of exercise training cohorts unable to independently assess effects of HIIT versus resistance training or age-by-sex interactions
Observational nature limits mechanistic insights into relationships between IMAT and key phenotypes
Difficult to discriminate IMAT from perimuscular adipose tissue (PMAT) using the segmentation technique

Implication

IMAT may contribute to insulin resistance in older muscle; leaves open whether exercise fully restores metabolic function.

Abstract

Intermuscular adipose tissue (IMAT) accumulates in the lower leg musculature of healthy older adults. IMAT was negatively associated with the rate of glucose infusion during a hyperinsulinemic-euglycemic clamp and muscle oxidative capacity. Exercise training decreased IMAT to a greater extent in young compared with older adults. Together these data support the implication that IMAT accumulation is linked with metabolic derangements in older adults but the restorative potential of exercise in older adults needs further evaluation.

Discussion

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Cite This Study

Alexander et al. (2025) studied this question.

synapsesocial.com/papers/6a70771efebe604dd7094165 https://doi.org/10.1152/japplphysiol.00719.2025

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Intermuscular adipose tissue in healthy human aging—effects of exercise training and implications to metabolic health

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

Intermuscular adipose tissue in healthy human aging—effects of exercise training and implications to metabolic health

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

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