Summary
It is widely accepted that aging is accompanied by remodelling of the immune system including thymic atrophy and increased frequency of senescent T cells, leading to immune compromise. ...However, physical activity, which influences immunity but declines dramatically with age, is not considered in this literature. We assessed immune profiles in 125 adults (55–79 years) who had maintained a high level of physical activity (cycling) for much of their adult lives, 75 age‐matched older adults and 55 young adults not involved in regular exercise. The frequency of naïve T cells and recent thymic emigrants (RTE) were both higher in cyclists compared with inactive elders, and RTE frequency in cyclists was no different to young adults. Compared with their less active counterparts, the cyclists had significantly higher serum levels of the thymoprotective cytokine IL‐7 and lower IL‐6, which promotes thymic atrophy. Cyclists also showed additional evidence of reduced immunesenescence, namely lower Th17 polarization and higher B regulatory cell frequency than inactive elders. Physical activity did not protect against all aspects of immunesenescence: CD28−veCD57+ve senescent CD8 T‐cell frequency did not differ between cyclists and inactive elders. We conclude that many features of immunesenescence may be driven by reduced physical activity with age.
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.
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.
Specific force (SF) has been shown to be reduced in some but not all studies of human aging using chemically skinned single muscle fibers. This may be due, in part, not only to the health ...status/physical activity levels of different older cohorts, but also from methodological differences in studying skinned fibers. The aim of the present study was to compare SF in fibers from older hip fracture patients (HFP), healthy master cyclists (MC), and healthy nontrained young adults (YA) using two different activating solutions. Quadriceps muscle samples and 316 fibers were obtained from HFPs (74.6 ± 4 years,
= 5), MCs (74.8 ± 1,
= 5), and YA (25.5 ± 2,
= 6). Fibers were activated (pCa 4.5, 15°C) in solutions containing either 60 mM N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid pH buffer (TES) or 20 mM imidazole. SF was determined by normalizing force to fiber cross-sectional area (CSA) assuming either an elliptical or circular shape and to fiber myosin heavy chain content. Activation in TES resulted in significantly higher MHC-I SF in all groups and YA MHC-IIA fibers, irrespective of normalization method. Although there were no differences in SF between the participant groups, the ratio of SF between the TES and imidazole solutions was lower in HFPs compared with YAs (MHC-I
< 0.05; MHC-IIA
= 0.055). Activating solution composition, as opposed to donor characteristics, had a more notable effect on single fiber SF. However, this two-solution approach revealed an age-related difference in sensitivity in HFPs, which was not shown in MCs. This suggests further novel approaches may be required to probe age/activity-related differences in muscle contractile quality.
Whether specific force (SF) decreases with advancing age in human single skeletal muscle fibers is uncertain. Equivocal published findings may be due to the different physical activity levels of the elderly cohorts studied and/or different chemical solutions used to measure force. We compared single fiber SF between young adults, elderly cyclists, and hip fracture patients (HFP) using two solutions. The solution used significantly affected force and revealed a difference in sensitivity of HFP muscle fibers.
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.
Arguably the best available depictions of the global physiological changes produced by age are the profiles of world record performance times in swimming, athletics, and cycling, depicting the ...trajectory of decline in maximal integrated physiological performance capability. The curves suggest that the aging process produces a synchronized, controlled decrease in physiological performance over the human lifespan. The shape of the performance profile by age is essentially independent of discipline, distance, or phenotype. Importantly, the specific times of performance are not the driving force in the production of the shape of the declining performance profile. We suggest that in these highly trained individuals the shape of the curve is generated by the aging process operating on a physiology optimized for any given age. We hypothesize that with adequate training this same profile and trajectory, but with lower performance times, would be generated by all individuals who engage in sufficient physical activity/exercise. Unlike performance, data obtained from examining individual physiological systems or tissues do not give information on the unceasing and changing global integrating functions of the aging process. However, these data do give valuable information about the integrity of physiological systems at a particular age and allow a direct comparison to be made between the effects of inactivity and physical activity/exercise. Being physically active has been shown to have global protective effects on physiological systems and thus facilitates the aging process by maintaining physiological integrity. There is emerging evidence which suggests that physiological regulation of aging may be multi-compartmentalized. We do not advocate exercise as a panacea, but all the evidence indicates that being physically active and exercising is far superior to any other alternative for achieving optimal aging.
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.
As the inherent ageing process affects every facet of biology, physiology could be considered as the study of the healthy human ageing process. Where biological health is affected by lifestyle, the ...continual and continuing interaction of this process with physical activity and other lifestyle choices determine whether the ageing trajectory is toward health or disease. The presentation of both these states is further modified in individuals by the interaction of inherent physiological heterogeneity and the heterogeneity associated with responses and adaptions to exercise. The range of heterogeneity in healthy physiology is circumscribed by the necessity to conform to that of the human species. Our hypothesis is that, when sufficient exercise is present, these multiple interactions appear to produce an ageing profile that, while functional ability is in decline, remains synchronous, coherent, and integrated throughout most of life. In the absence of sufficient physical activity, physiology over time is gradually deteriorating toward the production of a lifestyle disease. Here, the ageing process, interacting with individual physiological heterogeneity, probably determines the age of presentation of a disease as well as the order of presentation of subsequent diseases. In this article, we discuss this hypothesis and related concepts in the context of the trajectory of healthy and non-healthy human ageing.
Summary
In this study, results are reported from the analyses of vastus lateralis muscle biopsy samples obtained from a subset (n = 90) of 125 previously phenotyped, highly active male and female ...cyclists aged 55–79 years in regard to age. We then subsequently attempted to uncover associations between the findings in muscle and in vivo physiological functions. Muscle fibre type and composition (ATPase histochemistry), size (morphometry), capillary density (immunohistochemistry) and mitochondrial protein content (Western blot) in relation to age were determined in the biopsy specimens. Aside from an age‐related change in capillary density in males (r = −.299; p = .02), no other parameter measured in the muscle samples showed an association with age. However, in males type I fibres and capillarity (p < .05) were significantly associated with training volume, maximal oxygen uptake, oxygen uptake kinetics and ventilatory threshold. In females, the only association observed was between capillarity and training volume (p < .05). In males, both type II fibre proportion and area (p < .05) were associated with peak power during sprint cycling and with maximal rate of torque development during a maximal voluntary isometric contraction. Mitochondrial protein content was not associated with any cardiorespiratory parameter in either males or females (p > .05). We conclude in this highly active cohort, selected to mitigate most of the effects of inactivity, that there is little evidence of age‐related changes in the properties of VL muscle across the age range studied. By contrast, some of these muscle characteristics were correlated with in vivo physiological indices.
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.
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