Remodelling of the immune system with age - immunosenescence - is a substantial contributor to poor health in older adults, with increasing risk of infections, cancer and chronic inflammatory disease ...contributing to age-related multi-morbidity. What is seldom considered when examining the immune response of an aged individual is that the immune system is profoundly influenced by physical activity. Habitual physical activity levels decline with age, with significant consequences for muscle mass and function. Skeletal muscle is a major immune regulatory organ and generates a range of proteins, termed myokines, which have anti-inflammatory and immunoprotective effects. Several studies indicate that maintaining physical activity has immune benefits in older adults, for example, it reduces the systemic inflammation associated with chronic age-related diseases. Here, we discuss how physical activity can prevent or ameliorate age-related multi-morbidity by boosting immune function, and we consider whether physical activity could improve immunotherapy outcomes in age-related conditions such as cancer.
Human evolution suggests that the default position for health is to be physically active. Inactivity, by contrast, has serious negative effects on health across the lifespan. Therefore, only in ...physically active people can the inherent aging process proceed unaffected by disuse complications. In such individuals, although the relationship between age and physiological function remains complex, function is generally superior with health, well being, and the aging process optimized.
Acute skeletal muscle wasting in critical illness Puthucheary, Zudin A; Rawal, Jaikitry; McPhail, Mark ...
JAMA : the journal of the American Medical Association,
10/2013, Letnik:
310, Številka:
15
Journal Article
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Survivors of critical illness demonstrate skeletal muscle wasting with associated functional impairment.
To perform a comprehensive prospective characterization of skeletal muscle wasting, defining ...the pathogenic roles of altered protein synthesis and breakdown.
Sixty-three critically ill patients (59% male; mean age: 54.7 years 95% CI, 50.0-59.6 years) with an Acute Physiology and Chronic Health Evaluation II score of 23.5 (95% CI, 21.9-25.2) were prospectively recruited within 24 hours following intensive care unit (ICU) admission from August 2009 to April 2011 at a university teaching and a community hospital in England. Patients were recruited if older than 18 years and were anticipated to be intubated for longer than 48 hours, to spend more than 7 days in critical care, and to survive ICU stay.
Muscle loss was determined through serial ultrasound measurement of the rectus femoris cross-sectional area (CSA) on days 1, 3, 7, and 10. In a subset of patients, the fiber CSA area was quantified along with the ratio of protein to DNA on days 1 and 7. Histopathological analysis was performed. In addition, muscle protein synthesis, breakdown rates, and respective signaling pathways were characterized.
There were significant reductions in the rectus femoris CSA observed at day 10 (−17.7% 95% CI, −25.9% to 8.1%; P < .001). In the 28 patients assessed by all 3 measurement methods on days 1 and 7, the rectus femoris CSA decreased by 10.3% (95% CI, 6.1% to 14.5%), the fiber CSA by 17.5% (95% CI, 5.8% to 29.3%), and the ratio of protein to DNA by 29.5% (95% CI, 13.4% to 45.6%). Decrease in the rectus femoris CSA was greater in patients who experienced multiorgan failure by day 7 (−15.7%; 95% CI, −27.7% to 11.4%) compared with single organ failure (−3.0%; 95% CI, −5.3% to 2.1%) (P < .001), even by day 3 (−8.7% 95% CI, −59.3% to 50.6% vs −1.8% 95% CI, −12.3% to 10.5%, respectively; P = .03). Myofiber necrosis occurred in 20 of 37 patients (54.1%). Protein synthesis measured by the muscle protein fractional synthetic rate was depressed in patients on day 1 (0.035%/hour; 95% CI, 0.023% to 0.047%/hour) compared with rates observed in fasted healthy controls (0.039%/hour; 95% CI, 0.029% to 0.048%/hour) (P = .57) and increased by day 7 (0.076% 95% CI, 0.032%-0.120%/hour; P = .03) to rates associated with fed controls (0.065%/hour 95% CI, 0.049% to 0.080%/hour; P = .30), independent of nutritional load. Leg protein breakdown remained elevated throughout the study (8.5 95% CI, 4.7 to 12.3 to 10.6 95% CI, 6.8 to 14.4 μmol of phenylalanine/min/ideal body weight × 100; P = .40). The pattern of intracellular signaling supported increased breakdown (n = 9, r = −0.83, P = .005) and decreased synthesis (n = 9, r = −0.69, P = .04).
Among these critically ill patients, muscle wasting occurred early and rapidly during the first week of critical illness and was more severe among those with multiorgan failure compared with single organ failure. These findings may provide insights into skeletal muscle wasting in critical illness.
Analysis of world record performances by master athletes suggests an essentially linear decline with age until around the eighth decade after which performance decline accelerates. Because these ...records are obtained from highly trained individuals they can be viewed as being reflective of the diminution of integrative physiological prowess that occurs solely as a result of ageing, unaffected by the confounding effects of inactivity. It can also be argued that these performance profiles mirror and provide an insight into the trajectory of the physiology of the human ageing process. Here we propose a set point theory that hypothesises that a given threshold of physical activity is needed to age optimally and to maximise the ‘healthspan’. Exercising at levels below the set point will result in ageing being contaminated by the unpredictable and pathological effects of inactivity. Exercise above this threshold stimulates adaptations towards maximising athletic performance, but is unlikely to have further beneficial effects on health. Thus the decades‐long, controlled diminution in athletic performance, should not be seen as a disease process. The ageing process is separate from, and independent of, exercise‐mediated processes that maintain or adapt physiological function. Whether an understanding of these mechanisms will also help uncover mechanisms underpinning the ageing process itself is open to question. However, any model which does not take into account the effects of activity will not adequately describe the inherent ageing process.
Red: charts the uncertain health outcomes when activity is insufficent to counter the effects of inactivity. Green: Activity is sufficient to counter the effects of inactivity. Health and ageing are optimised. Gold: No further increases in health benefits or ageing trajectory. Further adaptations possible for improved athletic performance.
This brief review focuses on the relationships and interactions between human ageing, exercise and physiological function. It explores the importance of the selection of participants for ageing ...research, the strengths and deficiencies of both cross‐sectional and longitudinal studies, and the complexities involved in understanding time‐dependent, lifelong physiological processes. As being physically active is crucial to fostering healthy ageing, it is essential that participants in health and ageing research are defined in terms of their physical activity/exercise status as well as other lifestyle factors. Comparisons of exercisers with non‐exercisers has suggested that there is a mosaic of regulation of ageing both within and across physiological systems. We suggest that four broad categories exist which encompass this regulation. These are (i) systems and indices that are age dependent, but activity independent; (ii) systems that are age dependent, but also malleable by exercise; (iii) systems that are not age affected but are altered by exercise; and (iv) systems that are neither age nor activity dependent. We briefly explore the concept of a mosaic of regulation in a selection of physiological systems. These include skeletal muscle, the immune and endocrine systems, gastrointestinal as well as cognitive function. We go onto examine how these categories might fit within the broad framework of understanding the physiology of human ageing.
Schematic depiction of how healthy or diseased ageing phenotypes are the product of the interaction and regulation of physiological systems that can broadly be grouped into four categories on the basis of their malleability or otherwise to exercise and to the ageing process.
Changes in myonuclear architecture and positioning are associated with exercise adaptations and ageing. However, data on the positioning and number of myonuclei following exercise are inconsistent. ...Additionally, whether myonuclear domains (MNDs; i.e., the theoretical volume of cytoplasm within which a myonucleus is responsible for transcribing DNA) and myonuclear positioning are altered with age remains unclear. The aim of this investigation was to investigate relationships between age and activity status and myonuclear domains and positioning. Vastus lateralis muscle biopsies from younger endurance‐trained (YT) and older endurance‐trained (OT) individuals were compared with age‐matched untrained counterparts (YU and OU; OU samples were acquired during surgical operation). Serial, optical z‐slices were acquired throughout isolated muscle fibres and analysed to give three‐dimensional coordinates for myonuclei and muscle fibre dimensions. The mean cross‐sectional area (CSA) of muscle fibres from OU individuals was 33%–53% smaller compared with the other groups. The number of nuclei relative to fibre CSA was 90% greater in OU compared with YU muscle fibres. Additionally, scaling of MND volume with fibre size was altered in older untrained individuals. The myonuclear arrangement, in contrast, was similar across groups. Fibre CSA and most myonuclear parameters were significantly associated with age in untrained individuals, but not in trained individuals. These data indicate that regular endurance exercise throughout the lifespan might better preserve the size of muscle fibres in older age and maintain the relationship between fibre size and MND volumes. Inactivity, however, might result in reduced muscle fibre size and altered myonuclear parameters.
What is the central question of the study?
How do endurance exercise and the ageing process affect the positioning and number of myonuclei within muscle fibres?
What are the main findings and their importance?
There was reduced muscle fibre size, with smaller myonuclear domains and altered myonuclear domain scaling in older, untrained individuals. However, older trained individuals maintained similar muscle and myonuclear characteristics to younger trained individuals. This suggests that inactivity, rather than ageing, influences muscle fibre and myonuclear characteristics. These observations suggest that consistent endurance exercise over one's lifetime might help to preserve muscle fibre size and quality and myonuclear arrangement into old age.
Summary
The myogenic behaviour of primary human muscle precursor cells (MPCs) obtained from young (aged 20–25 years) and elderly people (aged 67–82 years) was studied in culture. Cells were compared ...in terms of proliferation, DNA damage, time course and extent of myogenic marker expression during differentiation, fusion, size of the formed myotubes, secretion of the myogenic regulatory cytokine TGF‐β1 and sensitivity to TGF‐β1 treatment. No differences were observed between cells obtained from the young and elderly people. The cell populations were expanded in culture until replicative senescence. Cultures that maintained their initial proportion of myogenic cells (desmin positive) with passaging (n = 5) were studied and compared with cells from the same individuals in the non‐senescent state. The senescent cells exhibited a greater number of cells with DNA damage (γ‐H2AX positive), showed impaired expression of markers of differentiation, fused less well, formed smaller myotubes and secreted more TGF‐β. The data strongly suggest that MPCs from young and elderly people have similar myogenic behaviour.
Loss of skeletal muscle mass and muscle weakness are common in a variety of clinical conditions with both wasting and weakness associated with an impairment of physical function. ...β-Hydroxy-β-methylbutyrate (HMB) is a nutrition supplement that has been shown to favorably influence muscle protein turnover and thus potentially plays a role in ameliorating skeletal muscle wasting and weakness.
The aim of this study was to investigate the efficacy of HMB alone, or supplements containing HMB, on skeletal muscle mass and physical function in a variety of clinical conditions characterized by loss of skeletal muscle mass and weakness.
A systematic review and meta-analysis of randomized controlled trials reporting outcomes of muscle mass, strength, and physical function was performed. Two reviewers independently performed screening, data extraction, and risk-of-bias assessment. Outcome data were synthesized through meta-analysis with the use of a random-effects model and data presented as standardized mean differences (SMDs).
Fifteen randomized controlled trials were included, involving 2137 patients. Meta-analysis revealed some evidence to support the effect of HMB alone, or supplements containing HMB, on increasing skeletal muscle mass (SMD = 0.25; 95% CI: –0.00, 0.50; z = 1.93; P = 0.05; I2 = 58%) and strong evidence to support improving muscle strength (SMD = 0.31; 95% CI: 0.12, 0.50; z = 3.25; P = 0.001; I2 = 0%). Effect sizes were small. No effect on bodyweight (SMD = 0.16; 95% CI: –0.08, 0.41; z = 1.34; P = 0.18; I2 = 67%) or any other outcome was found. No study was considered to have low risk of bias in all categories.
HMB, and supplements containing HMB, increased muscle mass and strength in a variety of clinical conditions, although the effect size was small. Given the bias associated with many of the included studies, further high-quality studies should be undertaken to enable interpretation and translation into clinical practice. The trial was registered on PROSPERO as CRD42017058517.
SJMSS paper of the year 2023 Harridge, Stephen D. R.
Scandinavian journal of medicine & science in sports,
February 2024, 2024-Feb, 2024-02-00, 20240201, Letnik:
34, Številka:
2
Journal Article
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