UK Research and Innovation (UKRI) – Written evidence (INQ0032)

 

 

Scientific basis

 

1.    Substantial progress has been made over the past three decades. We have some understanding of the health, lifestyle and life circumstances of an ageing population thanks to rich insights made possible via national resources such as the UK Biobank and the National Study of Health and Development (1946 cohort) - the longest continually running major birth cohort study in the world and one of the longest-running studies of human development. These have revealed a network of complex signaling pathways that are important for maintaining equilibrium in the human body in the face of external environmental changes.

2.    The 1946 birth cohort and other such epidemiological studies are now ripe for deeper mechanistic investigation, as are more younger birth cohorts, such as the Avon Longitudinal Study of Parents and Children (ALSPAC) – one of the few intergenerational cohorts in the world, which can shed light on socio-biomedical factors of the biology of ageing throughout the lifecourse.

3.    Areas where more research is required include the biology of the ageing process, from conception to old age, and spanning molecules and cells to systems, whole organisms and populations. Additionally, research is needed into the interdependencies of the underlying biological pathways, and their modulation by socio-economic, behavioural and lifestyle (nutrition, physical activity) and developmental factors. Further work is needed to establish the extent to which these impact on health in later life and crucially, biological “windows of opportunity” for early intervention as well as preventions of adverse effects of ageing, including multimorbidities – a condition where an individual or a population suffers from two or more long-term chronic disease, which may be both physical or mental.

4.    Priority areas for the bioscience underpinning ageing research include: the molecular and cellular basis of ageing, robust biomarkers of healthy ageing, genetic and epigenetic control, homeostasis, immune system effectiveness including immuno-senescence changes to gut microbiota, satiety and musculoskeletal health. Additionally, we are developing understanding of the decline of biological function with age such as mental and physical frailty as well as neuroscience and the development of cognitive and sensory (e.g. hearing, vision etc.) decline.

5.    We are beginning to understand the processes of ageing at a molecular level and how that increases the risk of multimorbidity. One of the major challenges is disentangling ‘normal’ aspects of ageing from changes related to common chronic diseases such as coronary heart disease, diabetes and arthritis. The understanding of degenerative chronic diseases is expanding and with it, the understanding of how individual behaviours and environment can slow or reverse some of these processes. However, we are in the early stages of this process and are only beginning to understand how external factors such as socioeconomic status relate to the biological processes of ageing[1].

6.    Studies of fundamental ageing processes at the population level are yet to demonstrate consistent results. For example, research on ‘biological clocks’ has found that many measures are poorly correlated[2],[3].

7.    The role of environment factors in the biological processes of ageing is a current topic of research. A recent pilot study[4] funded by the Natural Environment Research Council (NERC), part of UK Research and Innovation, concluded it is possible to take historical air pollution data through modelling and combine it with existing cohort studies in order to investigate the origins of dementia.

8.    The UK has a considerable infrastructure to enable analysis, including in particular a suite of world class longitudinal datasets such as Understanding Society, ELSA and SHARE. The combination of in-depth social information and biological data is important to enable scientific developments outlined above.

9.    The understanding of what constitutes a healthy lifestyle has a generally robust scientific foundation. However, further investigation into the effects of diet, physical activity, lifestyle, working pattern, stress and health during ageing, which includes anti-oxidant impact, change in appetite and the effect of ageing on response to dietary constituents, as well as longer-term dietary interventions, such as caloric restriction, is required.

10.                        The evidence is strong for certain aspects of public health advice, notably physical activity[5] and reduced sedentary behaviour (self-management of diabetes, undernutrition and smoking), whereas other lifestyle aspects including sleep, social engagement and appropriate help-seeking is less compelling as much of the evidence base is based on self-reported measures, which may not be robust, reliable or reproducible. Better and more robust biomarkers of ageing are needed to build a reliable scientific understanding of the processes that exacerbate or ameliorate the ageing process. For example, whilst there is good evidence on the benefits of physical activity in general, there is very little understanding of benefits of physical activity at a mechanistic level in humans, specifically the effect of physical activity on immunosenescence (the deterioration of the immune system due to natural ageing). A $160M programme, Molecular Transducers of Physical Activity Consortium (MoTrPAC)[6] will discover and perform preliminary characterisation of the range of molecular transducers (the "molecular map") that underlie the effects of physical activity in humans. The programme's goal is to study the molecular changes that occur during and after exercise and ultimately to advance the understanding of how physical activity improves and preserves health. The six-year programme is the largest targeted National Institute of Health investment of funds into the mechanisms of how physical activity improves health and prevents disease.

11.                        Evidence on mental health is more limited than physical health. Whilst longitudinal population studies are increasingly generating evidence of healthy lifestyles and cognition, most evidence comes from observational rather than intervention studies.

12.                        Randomised trials on the impact of lifestyle changes on long-term health at older ages are difficult to carry out due to cost, duration, and crucially, the limitations of the current clinical trial designs that exclude the ageing or elderly participants due to the complexities of multimorbidities and polypharmacy. This in turn leads to further rise in polypharmacy as most trials, and the resultant therapeutic drugs, are targeted at single diseases, whereas majority of the ageing population suffers from more than one chronic condition. This is one of the biggest healthcare burdens on society and the NHS[7] and there is an urgent need to develop “real world” clinical trials methodology. MRC Clinical Trials Unit at the UCL is at the forefront of clinical trials methodology research and the UK in general is world-leading in this field but more research to address the gaps in traditional and real-world trials is now needed.

13.                        Some of the newer non-clinical trial methodologies for establishing causality (for example, Mendelian Randomisation[8]) are important in this domain and can be applied to longitudinal cohort studies such as the English Longitudinal Study of Ageing (ELSA), the Economic and Social Research Council (ESRC) National Child Development Study (1958 cohort) and the Medical Research Council (MRC) National Survey of Health and Development[9].

14.                        In terms of practical impediments to research use, more clarity is needed on how to formulate, deliver and monitor interventional advice to ensure the maximum impact in health outcomes. Evidence is being sought by the £55m UK Prevention Research Partnership (UKPRP), part funded by UK Research and Innovation, to determine if modification in common environmental, social, and policy influences could be more effective than individually focused health promotion initiatives in reducing the incidence of non-communicable diseases. In terms of biological interventions, approaches including advanced data collection and analysis will be required to follow up the extensive epidemiological evidence generated over the last century.

15.                        Another issue is implementing ways to establish and sustain behaviour change. For example, although there have been great strides in combining pharmacological and behavioural methods of stopping smoking, continuous abstinence rates following interventions are still less than 25%. Similarly, the long-term impact of unsupervised exercise interventions among older people is limited, and techniques for modifying diets and reducing stress long term are poorly developed.

16.                        Access to nature has strong associations with health and wellbeing throughout life, as stated in the Government’s 25 Year Environment Plan. However, work continues to determine how this can be translated into policy. A recent NERC-funded study on Green Infrastructure to Promote Health and Wellbeing in an Ageing Population[10] developed robust protocols to evaluate the impact of improvements in urban green space on older adults’ physical activity and wellbeing.

17.                        An example of good practice in implementing sustained behaviour change is The Football Fans in Training (FFIT) programme, pioneered by researchers from the MRC / CSO Social and Public Health Sciences Unit in Glasgow. This is a healthy living and weight loss programme that is focused on physical activity and diet in overweight and obese men aged 35-65. It was developed and evaluated in a major research project led by the University of Glasgow and many Scottish Professional Football League clubs continue to offer the programme today[11]. Furthermore, this programme has been adapted and implemented worldwide, for example in Canada based on the success of the FFIT. It is now timely to build on this success and explore whether similar to the idea of precision prevention, policy implementation may also need careful stratification to the target approaches in most impactful manner. More public health and behavioural research would be needed to test and trial interventions in real world settings.

 

18.                        Integrative approaches to understanding of the biological mechanisms of ageing and ageing-related diseases, such as the ageing immune system, the role of inflammation in age-related dementia, chronobiology, senolytics such as rapamycin and the epigenetic clock, are increasing but translation of this knowledge into the clinic is yet to be achieved. The identification of biomarkers that predict healthy ageing and disease risk will represent a huge stride forward in the efforts to combat age-related disease and dysfunction.

19.                        Initiatives to address key early translational knowledge gaps such as the £42m UK Regenerative Medicine Platform can provide a strong platform from which to develop novel interventions. These impact areas include induced pluripotent stem cells, cellular reprogramming, autologous cell-based therapies for skeletal muscle regeneration, and stimulation of endogenous repair are emerging.

20.                        Current priority areas of biological and medical research (in general, not specifically related to ageing) include maintenance of function, the slowing of functional decline, prevention and early diagnosis of age-related diseases. Combined with advances in personalised medicine, the potential for targeted biological intervention for patients with genetic predispositions for certain conditions could be realised. Acceleration of the impact of research into age-related conditions such as inflammation, chronic disease, and multimorbidity is most likely to be achieved by implementing similar models to the UK Dementia Research Institute (UK DRI) and the National Innovation Centre for Ageing (NICA) which bring together scientists, industry, the NHS, the charitable and public sectors to bring products to market that optimise health and wellbeing as people age.

 

21.                        There has been considerable research into the behavioural and social determinants of health in later life[12]. This has led to the recognition of the cumulative impact of behaviour over time on long-term health conditions, and that the cumulative experience of unequal social, economic and environmental circumstances throughout life contributes to health inequalities in older age. Some aspects of behavioural and social determinants of health in old age are well understood, including:

 

22.                        In other areas there remains a need for more specific or in-depth analyses, including:

 

23.                        There is an important role for policy initiatives, beyond those directly related to health, to promote ageing well, whether this is in tackling the fear of crime, subsidising transport or providing better information to tackle the 'information poverty' of old age. We can do more to use behavioural science to design policies across a range of policy areas that can influence behaviours in ways that result in better long-term health and wellbeing. This also means designing traditional policy tools (such as incentives, information campaigns, treatments) with an appreciation of the way they may shape behaviour and outcomes as well as the way people's behaviour changes through the life cycle.

 

Technologies

 

24.                        It is worth stressing that ageing is a biological process, not a disease. However, with ageing, susceptibility to non-communicable diseases increases. Technologies will be key to prolonging healthy ageing and to facilitate treatment of diseases which increase in prevalence in older age cohorts.

25.                        Biological technologies and resources required include:

26.                        Biological tools required include:

27.                        The biological tools, technologies and resources outlined above are generally available for research purposes, but are often not developed specifically for ageing, and would require further development and translation for use in this area. They can largely be divided into two groups – potential treatments and prerequisites. Further translation is required to move from a lab bench to clinic for the majority of treatment options, and further integration into regulatory and legal frameworks is needed for the prerequisites.

28.                        Technologies that can facilitate detection and treatment of disease include the following:

 

29.                        "Through-life" design is key, rather than trying to redesign products and services specifically for the elderly; research into modular products, services and architecture, which can be adapted to the needs of people as they age, needs support, with a view to fast-track commercialisation.

30.                        To help ensure older people can benefit as much as possible from new technologies, the following needs to take place:

 

31.                        Technology can play a vital role in alleviating loneliness in older people, although it is not a substitute of social interactions. Population ageing studies have shown a growing trend in greater use of email, Twitter and Facebook among older people. However, a significant number of older people are not confident in using technology. There is therefore a need to ensure technology does not have negative consequences such as increasing inequalities of access or heightening sense of loneliness (see Q8). There is an aspect here of defining community beyond physical ones and considering the importance of virtual communities[19] in the future.

32.                        Additionally, more specific types of electronic technologies such as mental health and mindfulness apps are being developed. There is a lot of scope here for applications of immersive technology. While the focus at present is on immersive entertainment, the potential for both mental healthcare, increased social connectivity and physical activity is enormous; narrative designers from immersive technology and gaming could be hugely valuable, but interdisciplinary networks need careful and targeted brokering.

33.                        Increasing use of ‘mainstream’ technologies, such as voice-activated devices, in care settings can improve wellbeing outcomes by reducing social isolation. The devices are increasingly accessible and affordable; and some small-scale pilots have been undertaken at local authority level.

34.                        There is growing interest in ‘social robots’ globally, for example in Japan. However, these are less developed and diffused in the UK where the evidence base is under-developed and studies have tended to focus on pilots and prototypes. Policymakers and investors are still calling for robust evidence of application, implementation, uptake, long-term mechanisms and processes[20].

 

35.                        The digital switchover in 2025 has implications for technologies in current use as analogue devices will no longer function optimally. Most ‘telecare’ and technology used in care contexts is analogue.

36.                        There are known barriers to using digital technologies;

37.                        Some of the issues above will decrease as the oldest (least engaged) cohorts are replaced by those who are more familiar with new technology. However, even when this happens there are issues that relate to ageing that can inhibit technology use, for example visual impairments.

38.                        Barriers faced in bringing innovation into the market are:

39.                        Further research is required to develop appropriate tools, technologies and resources to study healthy ageing e.g. biomarkers and models. Overcoming these barriers to using technology and bringing innovation to market will require educating our innovators, making them aware of the problems and barriers and advising them how to overcome them. This requires a continued support to ensure effective collaboration between innovations and academic experts, as well as ensuring innovators can access suitable and diverse populations of older people for market research and product testing.

40.                        The Innovation and Knowledge Centre in Medical Technologies at the University of Leeds is a good model for transferring technologies from research to market more quickly[23]. Similarly, UKRI funded centers such as the National Innovation Centre for Ageing in Newcastle, the Manchester Institute for Collaborative Research on Ageing and the Helen Hamlyn Centre for Design at the Royal College of Art all have a specific focus on translation related to aspects of ageing.

 

Industrial strategy

41.                        Regenerative biology provides significant opportunities to increase health span. The shorter-term potential lies in targeting specific aspects of ill health common to ageing, such as hip replacements, and providing treatments which promote and prolong the healthy state, rather than requiring medical intervention.

42.                        Industry can assist in the translation process, by refining the broad range of potential treatments currently under investigation to a smaller number of procedures and interventions more likely to be practical. The UK has a substantial reputation in regenerative biology, with high levels of academic expertise. The NHS is a particular advantage for this area, being a centralised healthcare system, which can be a key stakeholder.

43.                        The greatest early gains in improving the health span are likely to stem from technologies for enabling ‘healthy ageing’. This encompasses a broad range of issues and incorporates aspects such as healthy lifestyles, financial wellbeing, social connectedness and environmental factors. There is no single recognised sector; rather healthy ageing markets offer opportunities for industries ranging from Fast-Moving Consumer Goods (FMCG), assistive technologies and MedTech, fit-tech through to service sectors such as architecture, marketing, financial services, utilities, artificial intelligence and sports and leisure.

44.                        There are opportunities for innovations in the prevention and early detection of disease, improved treatments, improved care pathways enabled by technology as well as improving the understanding of the role of cell senescence in the failure of organs and tissue that would allow better targeting of medicines and of the role of nutrition in managing ageing processes. Specifically, technology that facilitates real-time capture of clinically relevant health and lifestyle data, as well as novel methods for improving adherence and messaging to patients, could significantly advance the fundamental study of factors that influence a healthy lifespan.

45.                        The UK has the potential to be attractive in global markets in offering a platform for the design, development and market testing of healthy ageing innovations based on its integrated public health and care system, global-leading academic base in design and engineering and a strong policy legacy of supporting independent living.

 

46.                        A key gap in current markets is in the development of services offering comprehensive ‘solutions’ based on new technologies. Hampshire County Council’s telecare service is a good example where a service-based business model has achieved significant benefits using mature technologies.

47.                        There is a need for a stronger evidence base to understand factors affecting adoption and decision making by individuals and organisations. This is something that planned UKRI-led research under the Industrial Strategy Healthy Ageing challenge aims to address.

48.                        Additional work is needed on the integration of manufacturing and administration of cell-, gene- and tissue-based therapies in a clinical setting where pharmacy services and clinicians effectively become part of the supply chain for these delicate products. These are also reliant on further investment in the development of prognostic indicators of likelihood of treatment success for advanced therapies when being considered for individual patients.

49.                        Centers for Doctoral Training and Knowledge Transfer Partnerships are proven mechanisms to enable technology transferred from prototype to manufacturing. By increasing funding to these mechanisms we can create more and better connections, platforms, and exchanges between universities and business.

50.                        Better understanding is needed of creative Intellectual Property law and rights; more cross-pollination of design and STEM research; frameworks for the equivalent of "Technology Readiness Level" for creative and artistic/design output and innovation; retention of design expertise in public-funded R&D.

 

Healthier ageing

 

51.                        Ageing encompasses a complex landscape in which a broad range of themes come together to enable healthier, active and independent lives. Research needs to understand the complex interdependencies involved coupled with continued investment in research, innovation in services, technologies and infrastructure.

52.                        A focus on the 2035 target means that the most significant changes are likely to stem from supporting societal changes. Such changes will be dependent on:

53.                        With new challenges to longevity arising continually, it is important to monitor trends and continue to develop prevention strategies and treatments to enable increased health span. This will mean continued support for existing UKRI investments, such as:

 

 

54.                        Affordability universally influences the effectiveness of healthcare interventions and its effect on healthy ageing is one of a range of factors that require consideration with respect to health inequalities (discussed elsewhere, e.g. Q2 and 8) that determine quality of life in older age.

55.                        There is a body of evidence, notably from the longitudinal cohort data mentioned earlier, that shows that deprivation leads to shorter lifespans and longer periods lived in poor health. Socioeconomic factors contribute to inequalities in many health problems of older age including coronary heart disease, dementia, diabetes and frailty. Raising the health and wellbeing of less affluent sectors would help to achieve the Government’s aims without any other changes. Inequalities affect the uptake of technology; for example less healthy, older, female groups are more likely suffer digital exclusion[24]. There is a role for public service commissioners to address this access to services by provision through statutory services and through support for impact investment and social entrepreneurship.

56.                        UKRI research under the Industrial Strategy Healthy Ageing Challenge and ESRC’s Delivery Plan focus on ‘Changing Populations’, will explicitly include a focus on understanding inequalities and ensuring interventions to achieve healthy ageing ambitions are beneficial across social groups. A focus on enabling businesses to deliver the solutions through private investment could be expected to initially focus on sections of society able to pay, with some hope that as volumes grow, price will reduce and solutions become more affordable.

 

57.                        The impacts of a paradigm shift are extensive and complex, and living healthier and longer lives is not necessarily cost neutral. Issues that will arise include the extension of paid employment into older age, the rise in the dependency ratio, controlling health and social care costs and supporting the very old who may not be unhealthy but are frail.

58.                        There are social, economic and medical implications. Maintaining a population research infrastructure, particularly including longitudinal data, would be important to enable this modelling.

59.                        Research by the Institute of Fiscal Studies[25] and others to support the extension of the state pension age is relevant to understanding the economic benefits of longer working lives. Fulfilling employment is a key driver of healthy ageing – for financial wellbeing and in offering a sense of purpose and social connectivity.

60.                        The economic opportunity is also central to the development of the ISCF Healthy Ageing Challenge. The over- 50s held 68.3% of all UK household wealth and 77.3% of financial wealth in 2014. However, the Centre for Ageing Better, among others suggest that older markets are underserved: consumer marketing typically focuses on younger demographics; technology is typically developed by younger people with little input from those with ‘lived experience’ of ageing.

 

19 September 2019

 


[1] See e.g. McCrory C, et al. (2019) How does socio-economic position (SEP) get biologically embedded? A comparison of allostatic load and the epigenetic clock(s). Psychoneuroendocrinology 104:64-73.

[2] Marioni RE, et al. (2019) Tracking the epigenetic clock across the human life course: a meta-analysis of longitudinal cohort data. J Gerontol. Series A, Biol Sci Med Sci 74(1):57-61.

[3] Wang Q, Zhan Y, Pedersen NL, Fang F, & Hagg S (2018) Telomere length and all-cause mortality: a meta-analysis. Ageing research reviews 48:11-20.

[4] Modelling historical air pollution and dementia/cognitive decline - towards a life course approach, University of Edinburgh

[5] Diet, nutrition and the prevention of chronic diseases. WHO Technical Report Series, No. 916 (TRS 916)

[6] https://www.motrpac.org

[7] Multimorbidity – the biggest clinical challenge facing the NHS?

[8] Sheehan NA, Didelez V, Burton PR, Tobin MD (2008) Mendelian Randomisation and Causal Inference in Observational Epidemiology. PLoS Med 5(8): e177.

[9] Vanderweele TJ, Mathur MB, & Chen Y (2018) Outcome-wide longitudinal designs for causal inference: a new template for empirical studies.

[10] Green infrastructure and the Health and wellbeing Influences on an Ageing population (GHIA), University of Manchester

[11] https://dev.ffit.org.uk/

[12] 2015 BMA briefing paper on ‘Older people and the social determinants of health’ by Jessica Allen and Sorcha Daly, UCL Institute of Health Equity, available on the BMA website. The chapter by Michael Marmot and Richard Wilkinson is available to download here. https://www.oxfordscholarship.com/view/10.1093/acprof:oso/9780198565895.001.0001/acprof-9780198565895-chapter-13

[13] STFC Hartree project: Predicting care pathways following hospital discharge in collaboration with the Liverpool CCG

[14] STFC Hartree project: Analysis of Advice on Prescription targeting deprived areas in Liverpool

[15] University of Oxford: Machine Learning for Patient-Specific Predictive Healthcare Technologies via Intelligent Electronic Health Records (EPSRC grant EP/N020774/1).

[16] Using artificial intelligence to share control of a powered-wheelchair between a wheelchair user and an intelligent sensor system (EPSRC Grant EP/S005927/1)

[17] https://www.irc-sphere.ac.uk/

[18] ASPIRE: Automated Sensing & Predictive Inference for Respiratory Exacerbation, University of Oxford

[19] AHRC 2019 Delivery Plan, P28.

[20] Consilium Research & Consultancy for Skills for Care. (2018). Scoping study on the emerging use of Artificial Intelligence (AI) and robotics in social care, London: Skills for Care.

[21] https://www.ofcom.org.uk/

[22] Original citation: Damant, Jacqueline and Knapp, Martin (2015) What are the likely changes in society and technology which will impact upon the ability of older adults to maintain social (extra-familial) networks of support now, in 2025 and in 2040? Future of ageing: evidence review, Government Office for Science, UK, London, UK

[23] Medical Technologies, Innovation and Knowledge Centre, University of Leeds

[24] Digital inclusion in later life: cohort changes in internet use over a ten-year period in England”, Matthews et al, 2018 See https://www.cambridge.org/core/journals/ageing-and-society/article/digital-inclusion-in-later-life-cohort-changes-in-internet-use-over-a-tenyear-period-in-england/777293953F7631DA9CE4AC5D943DDF69

[25] Retiring at 65 no more? The increase in the state pension age to 66 for men and women, Cribb J & Emmerson C , 2019, See https://www.ifs.org.uk/publications/13949