An investigation into the relationship between age and physiological function in highly active older adults

摘要

Despite extensive research, the relationship between age and physiological function remains poorly characterised and there are currently no reliable markers of human ageing. This is probably due to a number of confounding factors, particularly in studies of a cross-sectional nature. These include inter-subject genetic variation, as well as inter-generational differences in nutrition, healthcare and insufficient levels of physical activity as well as other environmental factors. We have studied a cohort of highly and homogeneously active older male (n = 84) and female (n = 41) cyclists aged 55–79 years who it is proposed represent a model for the study of human ageing free from the majority of confounding factors, especially inactivity. The aim of the study was to identify physiological markers of ageing by assessing the relationship between function and age across a wide range of indices. Each participant underwent a detailed physiological profiling which included measures of cardiovascular, respiratory, neuromuscular, metabolic, endocrine and cognitive functions, bone strength, and health and well-being. Significant associations between age and function were observed for many functions. The maximal rate of oxygen consumption ( showed the closest association with age (r = −0.443 to −0.664; P < 0.001), but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The results of this cross-sectional study suggest that even when many confounding variables are removed the relationship between function and healthy ageing is complex and likely to be highly individualistic and that physical activity levels must be taken into account in ageing studies.Key Points class="unordered" style="list-style-type:disc"> The relationship between age and physiological function remains poorly defined and there are no physiological markers that can be used to reliably predict the age of an individual. This could be due to a variety of confounding genetic and lifestyle factors, and in particular to ill-defined and low levels of physical activity. This study assessed the relationship between age and a diverse range of physiological functions in a cohort of highly active older individuals (cyclists) aged 55–79 years in whom the effects of lifestyle factors would be ameliorated. Significant associations between age and function were observed for many functions. was most closely associated with age, but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The data suggest that the relationship between human ageing and physiological function is highly individualistic and modified by inactivity. class="head no_bottom_margin" id="__sec2title">IntroductionOver the past two centuries human life expectancy has more than doubled in the developed world (Oeppen & Vaupel, ), resulting in a dramatic increase in the number of older individuals. Advancing age is associated with declines in function which ultimately lead to a loss of independence accompanied by increased prevalence of age-associated diseases and frailty (Doherty, ). In many biological models of ageing, longevity is used as the primary outcome measure (Bartke et al. ; Tatar, ), but in humans this is arguably of less importance than the consequences of a deterioration in physiological function. In this regard healthy life expectancy, termed ‘the healthspan’, is not keeping pace with average life expectancy (House of Lords Science and Technology Committee, ), such that the years spent with poor health and disabilities in old age are increasing. Thus there is a drive to find strategies by which healthspan can be increased, optimal physiological function maintained and the trajectory towards frailty lowered (Kirkland & Peterson, ; Tatar, ). However, our understanding of the relationship between healthy ageing and physiological function is limited and no markers exist which can be used to estimate the age of an individual.A host of factors that are intrinsic to research on human ageing, particularly in studies with a cross-sectional design, confound our interpretation of the age–function relationship. These factors include genetic variation between participants, inter-generational lifestyle, socio-economic, nutritional, healthcare and other environmental differences, as well as variations in the criteria used for the selection of participants (Metter et al. ; Lazarus & Harridge, ). In particular, a lack of adequate physical activity is known to have serious negative effects on physiological function (Blair, ) and in cases of enforced inactivity (e.g. bed rest and micro gravity) this initiates a so-called ‘accelerated ageing’ process (Saltin et al. ; McGuire et al. ). Because the majority of the older population fail to meet the recommended guidelines for physical activity and are largely sedentary (Blair, ) the tendency is to assume that inactivity is the inevitable condition for humans (Booth & Lees, ). However, given that our genetic inheritance stems from a period when high levels of physical activity were likely to be the norm (Booth et al. ), it has been argued that being physically active should be considered the default position for maintaining health and physiological function throughout the life span (Booth & Lees, ; Lazarus & Harridge, href="#b49" rid="b49" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_426438851">2010). In this light, an age-related deterioration in function (or inferred deterioration in the case of cross-sectional studies) measured in populations of sedentary people does not reflect the biological ageing process, but should be described as being the product of the ageing process superimposed on a background of disuse.Consequently, the experimental design for the study reported here, which aimed to investigate the relationship between age and physiological function, was mandated by the following considerations. First, having decided that exercise was the default condition for optimal physiological status, all participants had to be highly physically active. Secondly, with a longer life span and closer proximity to thresholds of functional independence, particularly as a result of a lower muscle mass (Skelton et al. href="#b89" rid="b89" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_426438949">2002), the inclusion of females as well males was essential. Finally, although the indices to be measured would focus heavily on the systems critical for maintaining physical function and health in later life, particularly the cardiovascular and musculoskeletal systems, a wide range of other indices were also measured that would be indicative of good health. Therefore, a deep phenotyping of each individual was undertaken.The aim of the study was thus to determine the relationship between age and function in non-elite male and female exercisers aged 55–79 years using a wide range of physiological indices and then to determine if any given function(s) could serve as a marker(s) of ageing as defined by its ability to predict the age of a healthy individual. The overarching hypothesis of our study was that only in the physically active would the relationship between age and physiological function be reflective of the ageing process.