What is the cause of the ageing atrophy?

BackgroundAs muscle capillarization is related to the oxidative capacity of the muscle and the size of muscle fibres, capillary rarefaction may contribute to sarcopenia and functional impairment in older adults. Therefore, it is important to assess how ageing affects muscle capillarization and the interrelationship between fibre capillary supply with the oxidative capacity and size of the fibres.MethodsMuscle biopsies from healthy recreationally active young (22 years; 14 men and 5 women) and older (74 years; 22 men and 6 women) people were assessed for muscle capillarization and the distribution of capillaries with the method of capillary domains. Oxidative capacity of muscle fibres was assessed with quantitative histochemistry for succinate dehydrogenase (SDH) activity.ResultsThere was no significant age‐related reduction in muscle fibre oxidative capacity. Despite 18% type II fibre atrophy (P = 0.019) and 23% fewer capillaries per fibre (P < 0.002) in the old people, there was no significant difference in capillary distribution between young and old people, irrespective of sex. The capillary supply to a fibre was primarily determined by fibre size and only to a small extent by oxidative capacity, irrespective of age and sex. Based on SDH, the maximal oxygen consumption supported by a capillary did not differ significantly between young and old people.ConclusionsThe similar quantitative and qualitative distribution of capillaries within muscle from healthy recreationally active older people and young adults indicates that the age‐related capillary rarefaction, which does occur, nevertheless maintains the coupling between skeletal muscle fibre size and capillarization during healthy ageing.

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 69%

Coupling between skeletal muscle fiber size and capillarization is maintained during healthy aging

Barnouin

McPhee

Butler-Browne

et al. 2017

“…In addition, a continuous worsening of muscularity and visceral adiposity is generally seen with the ageing process. This change in body compositions has been shown to become pronounced around 50 years old, with faster progression noted after 60 years old 29, 30. In the present study, all body compositions (SMI, IMAC, and VSR) in younger donors (<50 years) were significantly better than those in older donors (≥50 years) in both men ( P < 0.001 each) and women ( P < 0.001 each).…”

Section: Discussionmentioning

confidence: 95%

Proposal for new selection criteria considering pre‐transplant muscularity and visceral adiposity in living donor liver transplantation

Hamaguchi

Kaido

Okumura

et al. 2018

BackgroundThe significance of pre‐operative body composition has recently attracted much attention in various diseases. However, cut‐off values for these parameters remain undetermined, and these factors are not currently included in selection criteria for recipients of living donor liver transplantation (LDLT).MethodsUsing computed tomography of 657 donors for LDLT, skeletal muscle mass, muscle quality, and visceral adiposity were evaluated by using skeletal muscle mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral‐to‐subcutaneous adipose tissue area ratio (VSR). Sex‐specific cut‐offs for SMI, IMAC, and VSR were determined, and correlations with outcomes after LDLT in 277 recipients were examined with the aim of establishing new selection criteria for LDLT.ResultsOn the basis of younger donor data, we determined sex‐specific cut‐off values for low SMI, high IMAC, and high VSR (mean ± 2 standard deviations). Patients with all three factors showed the lowest survival rate after LDLT (1 year survival rate, 41.2%; P < 0.001). On multivariate analysis, low SMI (P = 0.002), high IMAC (P = 0.002), and high VSR (P = 0.001) were identified as independent risk factors for mortality after LDLT. Based on these findings, we have excluded patients showing all three factors (low SMI, high IMAC, and high VSR) as candidates for LDLT since October 2016.ConclusionsUsing cut‐off values determined from healthy donors, we have established new selection criteria for LDLT including body composition, which should improve post‐transplant outcomes.

“…These include, but are not limited to, loss of muscle fibres37 and reduced myofibre CSA21, 38, 39 associated with degeneration and structural alterations of the NMJ,40, 41, 42 a decline in functional innervation (partial denervation)41, 43, 44 and loss of motor units 3, 44, 45. Although it is not justified to extrapolate results from transgenic animal models to human muscles (i.e.…”

Section: Introductionmentioning

confidence: 99%

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Sakellariou

Lightfoot

Earl

et al. 2017

Skeletal muscle is a major site of metabolic activity and is the most abundant tissue in the human body. Age‐related muscle atrophy (sarcopenia) and weakness, characterized by progressive loss of lean muscle mass and function, is a major contributor to morbidity and has a profound effect on the quality of life of older people. With a continuously growing older population (estimated 2 billion of people aged >60 by 2050), demand for medical and social care due to functional deficits, associated with neuromuscular ageing, will inevitably increase. Despite the importance of this ‘epidemic’ problem, the primary biochemical and molecular mechanisms underlying age‐related deficits in neuromuscular integrity and function have not been fully determined. Skeletal muscle generates reactive oxygen and nitrogen species (RONS) from a variety of subcellular sources, and age‐associated oxidative damage has been suggested to be a major factor contributing to the initiation and progression of muscle atrophy inherent with ageing. RONS can modulate a variety of intracellular signal transduction processes, and disruption of these events over time due to altered redox control has been proposed as an underlying mechanism of ageing. The role of oxidants in ageing has been extensively examined in different model organisms that have undergone genetic manipulations with inconsistent findings. Transgenic and knockout rodent studies have provided insight into the function of RONS regulatory systems in neuromuscular ageing. This review summarizes almost 30 years of research in the field of redox homeostasis and muscle ageing, providing a detailed discussion of the experimental approaches that have been undertaken in murine models to examine the role of redox regulation in age‐related muscle atrophy and weakness.