Associations between body composition and gait-speed decline: results from the Health, Aging, and Body Composition study

Beavers, Kristen M.; Beavers, Daniel P.; Houston, Denise K.; Harris, Tamara B.; Hue, Trisha F.; Koster, Annemarie; Newman, Anne B.; Simonsick, Eleanor M.; Studenski, Stephanie A.; Nicklas, Barbara J.; Kritchevsky, Stephen B.

doi:10.3945/ajcn.112.047860

Cited by 217 publications

(186 citation statements)

References 34 publications

(41 reference statements)

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“…In addition, IMAT has been shown to be a significant predictor of impaired mobility in older adults 40, 41. The suggested synergistic implications of changes in muscle mass and adiposity on mobility in the frail elderly42 point to possible opportunities for drugs that act on both muscle and fat tissues.…”

Section: Discussionmentioning

confidence: 99%

Effect of bimagrumab on thigh muscle volume and composition in men with casting‐induced atrophy

Rooks¹,

Laurent

Præstgaard³

et al. 2017

J cachexia sarcopenia muscle

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BackgroundPatients experiencing disuse atrophy report acute loss of skeletal muscle mass which subsequently leads to loss of strength and physical capacity. In such patients, especially the elderly, complete recovery remains a challenge even with improved nutrition and resistance exercise. This study aimed to explore the clinical potential of bimagrumab, a human monoclonal antibody targeting the activin type II receptor, for the recovery of skeletal muscle volume from disuse atrophy using an experimental model of lower extremity immobilization.MethodsIn this double‐blind, placebo‐controlled trial, healthy young men (n = 24; mean age, 24.1 years) were placed in a full‐length cast of one of the lower extremities for 2 weeks to induce disuse atrophy. After cast removal, subjects were randomized to receive a single intravenous (i.v.) dose of either bimagrumab 30 mg/kg (n = 15) or placebo (n = 9) and were followed for 12 weeks. Changes in thigh muscle volume (TMV) and inter‐muscular adipose tissue (IMAT) and subcutaneous adipose tissue (SCAT) of the thigh, maximum voluntary knee extension strength, and safety were assessed throughout the 12 week study.ResultsCasting resulted in an average TMV loss of −4.8% and comparable increases in IMAT and SCAT volumes. Bimagrumab 30 mg/kg i.v. resulted in a rapid increase in TMV at 2 weeks following cast removal and a +5.1% increase above pre‐cast levels at 12 weeks. In comparison, TMV returned to pre‐cast level at 12 weeks (−0.1%) in the placebo group. The increased adiposity of the casted leg was sustained in the placebo group and decreased substantially in the bimagrumab group at Week 12 (IMAT: −6.6%, SCAT: −3.5%). Knee extension strength decreased by ~25% in the casted leg for all subjects and returned to pre‐cast levels within 6 weeks after cast removal in both treatment arms. Bimagrumab was well tolerated with no serious or severe adverse events reported during the study.ConclusionsA single dose of bimagrumab 30 mg/kg i.v. safely accelerated the recovery of TMV and reversal of accumulated IMAT following 2 weeks in a joint‐immobilizing cast.

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Section: Discussionmentioning

confidence: 99%

Effect of bimagrumab on thigh muscle volume and composition in men with casting‐induced atrophy

Rooks¹,

Laurent

Præstgaard³

et al. 2017

J cachexia sarcopenia muscle

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“…Reversal of type II fiber atrophy as a result of vitamin D supplementation is thought to account for approximately 20 % lower risk of falling [68]. Vitamin D deficiency apart from the atrophy of type II fibers in these individuals enables fat infiltration and consequently fibrosis (fibrosis is observed in different tissues including the muscle due to excess fat accumulation) which are important factors underpinning muscle quality and also may be a predictor of muscle function in older adult [69]. In closing, based on the available literature, we propose that vitamin D is beneficial for individuals since it increases muscle protein synthesis, adenosine triphosphate (ATP) concentration, strength, jump height, jumping and sprinting velocity and power, and aerobic and anaerobic exercise capacity.…”

Section: Implications Of These Data On Physical Activity and Exercisementioning

confidence: 99%

Vitamin D and Physical Activity

Koundourakis¹,

Margioris²

2017

A Critical Evaluation of Vitamin D - Basic Overview

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Vitamin D is synthesized in the skin following exposure to ultraviolet radiation, producing cholecalciferol, while only a small percentage of the circulating vitamin D is of exogenous origin deriving from food. Following two sequential hydroxylations, in the liver and in the kidneys, vitamin D is fully activated. Although its role in bone physiology and calcium homeostasis is well documented, there is emerging evidence that vitamin D exerts a plethora of additional effects on most tissues regulating the musculoskeletal, cardiovascular, and immune systems as well as energy homeostasis. Its deficiency/insufficiency poses a major public health problem observed in all age groups and regardless of latitude and insolation. In muscles, vitamin D deficiency is associated with a decline in neuromuscular function including muscular strength, walking speed, balance, jumping and sprinting performance, and aerobic capacity, although the evidence is still weak regarding its effects in the young and the athletes. Supplementation counteracts the negative effects of vitamin D deficiency on performance although in individuals with adequate levels of vitamin D, additional supplementation does not appear to enhance further physical capabilities. The aim of this chapter is to review our current understanding of diverse effects of vitamin D in physical performance in athletic and nonathletic populations.

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“…Intramuscular adipose tissue—here defined as clusters of adipocytes interspersed between skeletal muscle fibres—is generally associated with systemic insulin resistance,18, 19 decreased muscle strength20 and, in older adults, impaired mobility 21, 22, 2324.…”

Section: Introductionmentioning

confidence: 99%

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

Gorski

Mathes

Krützfeldt

2018

J cachexia sarcopenia muscle

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BackgroundIntramuscular fatty infiltration is generally associated with the accumulation of white adipocytes in skeletal muscle and unfavourable metabolic outcomes. It is, however, still unclear whether intramuscular adipocytes could also acquire a brown‐like phenotype. Here, we detected intramuscular expression of brown adipocyte markers during fatty infiltration in an obesity‐resistant mouse strain and extensively compared the potential of two different stem cell populations residing in skeletal muscle to differentiate into brown‐like adipocytes.MethodsFatty infiltration was induced using intramuscular glycerol or cardiotoxin injection in the tibialis anterior muscles of young or aged 129S6/SvEvTac (Sv/129) mice or interleukin‐6 (IL‐6) knockout mice, and the expression of general and brown adipocyte markers was assessed after 4 weeks. Fibro/adipogenic progenitors (FAPs) and myogenic progenitors were prospectively isolated using fluorescence‐activated cell sorting from skeletal muscle of male and female C57Bl6/6J and Sv/129 mice, and monoclonal and polyclonal cultures were treated with brown adipogenic medium. Additionally, FAPs were differentiated with medium supplemented or not with triiodothyronine.ResultsAlthough skeletal muscle expression of uncoupling protein 1 (Ucp1) was barely detectable in uninjected tibialis anterior muscle, it was drastically induced following intramuscular adipogenesis in Sv/129 mice and further increased in response to beta 3‐adrenergic stimulation. Intramuscular Ucp1 expression did not depend on IL‐6 and was preserved in aged skeletal muscle. Myogenic progenitors did not form adipocytes neither in polyclonal nor monoclonal cultures. Fibro/adipogenic progenitors, on the other hand, readily differentiated into brown‐like, UCP1+ adipocytes. Uncoupling protein 1 expression in differentiated FAPs was regulated by genetic background, sex, and triiodothyronine treatment independently of adipogenic differentiation levels.ConclusionsIntramuscular adipogenesis is associated with increased Ucp1 expression in skeletal muscle from obesity‐resistant mice. Fibro/adipogenic progenitors provide a likely source for intramuscular adipocytes expressing UCP1 under control of both genetic and hormonal factors. Therefore, FAPs constitute a possible target for therapies aiming at the browning of intramuscular adipose tissue and the metabolic improvement of skeletal muscle affected by fatty infiltration.

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Associations between body composition and gait-speed decline: results from the Health, Aging, and Body Composition study

Abstract: High and increasing thigh intermuscular fat are important predictors of gait-speed decline, implying that fat infiltration into muscle contributes to a loss of mobility with age. Conversely, a decreasing thigh muscle area is also predictive of a decline in gait speed.

Cited by 217 publications

References 34 publications

Effect of bimagrumab on thigh muscle volume and composition in men with casting‐induced atrophy

Effect of bimagrumab on thigh muscle volume and composition in men with casting‐induced atrophy

Vitamin D and Physical Activity

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

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