Associations of muscle lipid content with physical function and resistance training outcomes in older adults: altered responses with metformin

Abstract

Preserving muscle mass and strength is critical for long-term health and longevity. Age-related muscle lipid accumulation has been shown to be detrimental to muscle health. In healthy older individuals, we sought to determine whether muscle lipid content, determined from computed tomography, is associated with selfreported physical function, laboratory-measured performance, and the response to progressive resistance training (PRT), and how metformin may alter these responses (N = 46 placebo, 48 metformin). Using multiple linear regression models adjusted for confounders in a large cohort, we show that intermuscular adipose tissue (IMAT) was not associated with baseline function or response to PRT, contrary to previous reports. On the other hand, thigh muscle density (TMD), as an indicator of intra-and extramyocellular lipid (IMCL and EMCL),

Key concepts in muscle regeneration: muscle “cellular ecology” integrates a gestalt of cellular cross-talk, motility, and activity to remodel structure and restore function

“…The timing by which inflammation is resolved has a major impact on functional recovery, as is the timing of vascular regeneration to ensure blood supply for debris removal and support regenerating tissue. Adiposity within muscle fascicles and the level of physical activity prior to an injury also play into the timing and extent of recovery, along with stresses of metabolic disease, transient systemic conditions, and/or the secondary impact of genetic, biochemical, developmental or epigenetic modifications to cells or molecules that mediate the outcome of regeneration, as reviewed elsewhere (Urso 2013 ; Mok et al 2017 ; Robinson and Dilworth 2018 ; Mitchell et al 2019 ; Long et al 2021 ; Machado et al 2021 ; Vechetti et al 2021 ; Wen et al 2021 ).…”

Potential Benefits of Combined Statin and Metformin Therapy on Resistance Training Response in Older Individuals

“…Other work has shown that metformin use can impact insulin growth factor levels (IGF-1) following a single bout of resistance exercise ( Moreno-Cabañas et al, 2022 ). In our subsequent follow-up analyses, we showed that metformin administration primarily affected those with unhealthy muscle lipid profiles prior to beginning their resistance exercise program ( Long et al, 2021 ). Therefore, our work shows that as a monotherapy co-prescribed with exercise, metformin blunts desired PRT responses in healthy older adults.…”

“…Complete details, methods, and subject demographics of those completing the MASTERS trial have been reported elsewhere ( Long et al, 2017 ; Walton RG. et al, 2019 ; Long et al, 2021 ).…”

Potential nutritional strategies to prevent and reverse sarcopenia in aging process: Role of fish oil-derived ω-3 polyunsaturated fatty acids, wheat oligopeptide and their combined intervention

“…For example, increased ectopic lipid is a consequence of aging. It results in lipid-rich muscle with reduced muscle density and profound negative consequences by increased lipid infiltration within muscle fibers and adipocytes between muscle fibers [49] . The changes in adipose tissue function and distribution with aging affect the secretion of adipose tissue derived hormones and adipokines, and then contribute to a chronic state of low-grade systemic inflammation [50] .…”