Metformin promotes healthspan by attenuating frailty and preserving musculoskeletal function–structure in middle-aged mice

Apr 9, 2026Biogerontology

Metformin may improve healthy aging by reducing frailty and protecting muscle and bone in middle-aged mice

AI simplified

Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

Metformin treatment in middle-aged mice resulted in significantly attenuated frailty scores and preserved musculoskeletal health.

Midlife metformin treatment began at 30 weeks and continued until 53 weeks of age.
Treated mice maintained body weight comparable to young adult controls, preventing excessive age-related weight gain.
Frailty scores based on clinical and performance evaluations were significantly improved in metformin-treated mice.
Muscle strength, endurance, and mass were preserved, with increased muscle fiber size and enhanced capillary density.
Bone integrity was maintained, indicated by preserved trabecular architecture and osteoblast abundance.
Metformin supported locomotor function by preserving gait parameters and knee joint structure.

AI simplified

As global life expectancy rises, age-related musculoskeletal decline poses a growing public health challenge-impairing mobility, increasing frailty, and diminishing quality of life for billions worldwide. Functional deterioration often begins in midlife, yet effective early interventions remain limited. Metformin, a widely prescribed antidiabetic drug, has shown geroprotective potential. However, its capacity to preserve musculoskeletal health during early aging remains poorly defined. Addressing this gap is critical to developing scalable, cost-effective strategies to extend healthspan. Here, we investigated the effects of midlife metformin treatment in male C57BL/6 J mice by comparing young, untreated middle-aged, and metformin-treated middle-aged groups. Metformin treatment was initiated at 30 weeks of age and continued through 53 weeks. Frailty was evaluated using composite clinical and functional indices, while musculoskeletal health was assessed through motor tests and detailed histological analyses of muscle, bone, and joint tissues. Metformin-treated middle-aged mice maintained body weight comparable to that of young adult controls, preventing excessive age-associated weight gain. Both clinical and performance-based frailty scores were significantly attenuated. Muscle strength, endurance, and mass were preserved, alongside increased muscle fiber size, enhanced capillary density, and reduced fibrotic remodeling. Bone integrity was similarly maintained, evidenced by preserved trabecular architecture, osteoblast abundance, and collagen organization. Additionally, metformin supported locomotor function by preserving gait parameters and knee joint structure, including articular cartilage thickness and chondrocyte integrity. Collectively, these findings demonstrate that metformin administration supports healthspan by attenuating frailty and preserving musculoskeletal integrity in middle-aged mice, reinforcing its potential as a scalable geroprotective intervention targeting early aging.

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text (HTML) ↗

Metformin promotes healthspan by attenuating frailty and preserving musculoskeletal function–structure in middle-aged mice

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief