University of Birmingham MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research – Written evidence (INQ0056)

 

The MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research (CMAR) welcomes the opportunity to provide written evidence to the inquiry into Ageing: Science, Technology and Healthy Living. The Centre is co-hosted by the University of Birmingham and the University of Nottingham and its members have generated an extensive portfolio of scientific research in the mechanisms driving musculoskeletal ageing and the application of nutrition/physical activity/ exercise studies across diverse populations of older adults presenting across the spectrum of musculoskeletal function, including progression into age related disease.

 

In response to Question1: How complete is the scientific understanding of the biological processes of ageing and their epidemiologies (including the relative roles of genetics, epigenetics, lifestyle, environment, etc.)?

The contribution of genetics, epigenetics, lifestyle, environment, and periods of ill health are recognized as contributors to biological ageing processes, however their relative contribution to ageing is unknown and difficult to untangle. This is a key issue. Nevertheless, the fact that some traits of biological ageing, e.g. sarcopenia, can be altered positively by lifestyle intervention suggests this is an issue that warrants greater investigation. Importantly, the fact that several features of ageing can be induced in young people simply by making them inactive, e.g. muscle atrophy, insulin resistance, and muscle strength and power loss, points to biological ageing being masked by modifiable lifestyle factors that are not truly age related. This also necessitates further consideration. Significantly, any investigation needs to be conducted in humans as a difference of opinion on which biological processes predominate exists in no small part due to the unchecked translation of data derived from animals, which are known to differ in metabolic stability compared to humans (particularly when immature animals are used) [Demetrius L. Of mice and men - When it comes to studying ageing and the means to slow it down, mice are not just small humans. Embo Reports 2005; 6:S39-S44], and the lack of appropriately detailed and longitudinal human based investigation.

 

In response to Question 2: How firm is the scientific basis for public health advice about healthy lifestyles as a way to increase health span, including physical health and mental health?

Several CMAR members contributed to the recent update of the 2011 UK Chief Medical Officers physical activity guidelines: The latest guidelines were launched on the 07 September 2019 (no doubt the guidelines will be brought to the Committee’s attention by other contributors). The evidence supporting the guidelines was submitted as a technical report compiled by a number of expert working groups. Two members (Greig, Stathi) of the MRC-Arthritis Research UK Centre for Musculoskeletal Research (CMAR), whose research was cited in the technical report, are members of the older adult working group who evaluated the current scientific evidence in a number of areas relevant to physical activity and the health of older people. The evidence was taken from pooled analyses, meta-analyses and systematic reviews, recent national evidence reviews and additional articles identified by the working group. The working group reported that there was strong evidence to support the benefits of physical activity for physical and mental health in older adults, in addition to reducing the risk of developing dementia. However a number of knowledge gaps in the scientific literature exist and these were highlighted in the final group working paper as research recommendations (http://www.bristol.ac.uk/media-library/sites/sps/documents/cmo/older-adults-technical-report.pdf; please refer to page 32 also page 18 of the sedentary behaviour working paper prepared by the sedentary behaviour working group http://www.bristol.ac.uk/media-library/sites/sps/documents/cmo/sedentary-behaviour-technical-report.pdf  which included CMAR member, Fenton). The following paragraphs highlight those recommendations which are foci of current research endeavour within our Centre. Continuing research is crucial in terms of not only  the enhancement of our scientific understanding of the benefits of physical activity/ exercise for older adults, but also to ensure that each iteration of the CMO physical activity guidelines which translate knowledge and understanding into advice informing policy and practice, are robust and up to date.

  1. ‘There is a relative paucity of (sedentary behaviour) research in older adults, and in particular frail older adults’. Interventions in older adults to reduce sedentariness rather than increasing moderate to vigorous activity are a current hot topic in physical activity/ inactivity research. Increasing light physical activity through reducing sitting time may be more easily tolerated by frailer older adults with mobility limitation. Recent (unpublished) research from our group has shown that acute periods of sitting time induce significant increases in blood pressure in older adults. In addition, our group has published the first study to examine the implications of sedentary behaviour for endothelial function in rheumatoid arthritis, reporting significant cross-sectional associations between self-reported sitting time (min/week), and microvascular endothelium-dependent function [Fenton SAM et al., Sitting time is negatively related to microvascular endothelium-dependent function in rheumatoid arthritis. Microvasc Res. 2018 May;117:57-60]. A recent systematic review by our group [Aunger J et al., Interventions targeting sedentary behavior in non-working older adults: a systematic review. Maturitas. 2018 Oct;116:89-99], has highlighted the paucity of intervention studies to reduce sitting time in older adults; this represents a burgeoning area of research interest. Currently we do not know the threshold of activity required to ameliorate the adverse effects of sedentary time which limits the advice we can give to older adults and those who care for them.
  2. ‘Determine the effects of HIIT on hard clinical end points in older adults’. High intensity interval training (HIIT) has received much media attention. Our Centre has a research interest in high intensity interval training (HIIT) in older adults since short burst of high intensity exercise may be more readily adopted compared with longer bouts of moderate exercise. We have shown that HIIT can modify cardio-metabolic risk factors in adults at risk of developing diabetes [Phillips BE et al., A practical and time-efficient high-intensity interval training programme modifies cardio-metabolic risk-factors in adults at risk for developing Type II diabetes. Front Endocrinol. 2017;8:229]. In addition, we have shown that ten weeks of high intensity interval walk training is associated with improved fitness and reduced disease activity and improved innate immune function in older adults with rheumatoid arthritis [Bartlett D et al., Ten weeks of high intensity interval walk training is associated with reduced disease activity and improved innate immune function in older adults with rheumatoid arthritis: a pilot study. Arthr Res Ther 20: article 127].
  3. ‘Understand to what extent overall and HRQoL (health-related quality of life), social, isolation, wellbeing and psychological outcomes derived from physical activity participation are dose- or mode dependent’. We have systematically reviewed the evidence that physical activity helps to reduce social isolation and/or loneliness and found it to be limited [Shvedko A et al., Physical Activity Intervention for Loneliness (PAIL) in community-dwelling older adults: protocol for a feasibility study. Pilot Feasibility Stud. 2018 Dec 19;4:187].

‘Explore the impact of PA (physical activity) and SB (sedentary behaviour) on severe mental health illness’. In terms of the effects of exercise on mental health, we have published a systematic review and meta-analysis showing that when exercise is compared to non-exercise comparators and participants are adults with a depression diagnosis recruited via mental health services, the antidepressant effect of exercise is large (0.70) with low heterogeneity and no publication bias [Morres ID et al., Aerobic exercise for adult patients with major depressive disorder in mental health services: A systematic review and meta-analysis. Depress Anxiety. 2019 Jan;36(1):39-53]. This review has already been cited by many media/ organisations.

 

In summary, although the scientific basis underpinning the physical activity advice we may give to older adults is evolving/ improving, we need to heed the future research recommendations highlighted in the technical report. This will ensure the continuing relevance of the physical activity guidelines in terms of being a scientifically informed, public facing, practical interpretation of the evidence.

 

In response to Question 3: Which developments in biomedical science are anticipated in the coming years, in time to contribute to the Government’s aim of five more years of healthy and independent life by 2035?

Research areas may include:

 

Modern medicine and improved public welfare have done an excellent job at extending lifespan. The issue is that increasing healthspan in tandem has not occurred. Drug based approaches aimed at increasing healthspan have also not emerged to date, e.g. anabolic drug intervention to increasing muscle mass in older people have failed for several reasons, including lack of functional gains. Perhaps more importantly, modifications in lifestyle seem more likely to extend healthspan than pharmacological intervention given the evidence presented from energy restriction and exercise intervention studies in humans. In that respect, developments in omics technologies and MR imaging are likely to give greatest insight into the effectiveness of lifestyle intervention and biomarkers of effective intervention. Again, it is of utmost importance that these investigations are performed in people, in longitudinal study designs using rigorous protocols and gold-standard end point measurements.  This latter point has limited insight to date, but is likely to be the best mechanism to achieve a personalized medicine approach, i.e. the effectiveness of personalized medicine will be very much dependent on the extent to which any individual can be phenotyped.  

 

In response to question 11: How feasible is the Government’s aim to provide five more years of health and independence in old age by 2035?

Based on Office of National Statistics data (Office of National Statistics, ‘Past and projected data from the period and cohort life tables, 2016-based, UK: 1981 to 2066’), to achieve this Government objective the average healthy life expectancy will have to increase by nearly six months every year, which is ambitious. The response should involve a co-ordinated effort – please see The Physiological Society Report Growing Older, Better: Ensuring a physiology-based response to the Government’s Ageing Society Grand Challenge that summarises evidence and discussions with over 60 experts in lifelong health and Government policy across research, policy and funding.

 

Contributors to this response:

Dr Carolyn Greig

Prof Paul Greenhaff

 

20 September 2019