Professor Lynne Cox, University of Oxford – Written evidence (INQ0034)

 

Scientific basis

 

  1.              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.)?

 

  1.              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?

That depends on your definition of ‘healthy’ lifestyle. Whatever diet or exercise regime you favour, it does appear that caloric restriction and exercise remain the most robust extenders of healthy lifespan, at least in rodents and monkeys. Exercise needs to be both weight-bearing (for bones), aerobic (for cardiovascular system) and cognitively demanding (for neuroprotection). Older people who undertake very high levels of exercise appear to have decreased levels of chronic inflammation, a potential driver of multiple ARDs. Lack of sleep, exposure to pollution and chronic low-grade stress are also important factors in poor health yet public health messages about sleep, particularly, are non-existent. This is concerning given data on social media use by young people impacting on already low sleep levels. Dementia risk increases with lack of sleep, as do cancer and diabetes; potential biological mechanisms are being researched including ‘brain cleaning’ through the glymphatic system. The gig economy, job insecurity and an unhealthy work ethic promote seriously unhealthy behaviours around sleep. Pollution increases cell senescence (even in pregnancy, adversely affecting the unborn child) and premature onset of ARDs – poorer people are more exposed to pollutants and this has epigenetic as well as direct effects on them and even their unborn offspring, reinforcing polarization between rich and poor in terms of life expectancy and most importantly healthy life expectancy. Stress is associated with shorter telomeres (ends of chromosomes) which drives premature cell senescence and consequent higher levels of inflammation and ARDs. Job, housing and food insecurity all contribute, as does loneliness – stress and depression are major suppressors of the immune system, increasing disease susceptibility.

 

a. What are the practical impediments for this advice being acted on?

Junk food, alcohol and smoking are addictive, activating dopaminergic reward centres in the brain; we evolved to conserve energy and consume (rarely available) high fat-high sugar food; we are not evolutionarily adapted to an environment of instant-access food. Sedentary occupations are utterly inconsistent with our evolution. Worryingly, a raft of recent studies suggest sugar substitutes lead rapidly to metabolic syndrome and pre-diabetes, predisposing to diabetes – the sugar tax may have a wholly adverse and unexpected impact on long term health, even if it protects childhood dentition. Access to health care and health education is patchy, and educational poverty can lead to lifelong low earnings potential with poor diet and housing – junk food is somehow perceived as cheap, perhaps because of lack of cultural exposure to home-cooked nutritious meals. Meals cooked from scratch require time, knowledge, suitable equipment (including energy costs e.g. for ovens/hobs), skill and ingredients; this also usually requires forward planning and executive skills. An emphasis on embedding exercise as a natural part of life (not just regimented and off-putting PE) and basic cooking of nutritious meals may need to be a core valued part of school curricula from early years through to sixth form, as fewer young people have exposure and teaching at home. Exercise for adults may need subsidised/free to access community clubs for fun activities eg football, netball, badminton, dance, tai chi etc for all ages; fitness shouldn’t be just the domain of the rich, and it should be enjoyable and sociable.

 

b. Are there examples of good practice in the UK/devolved nations, or elsewhere?

Countries have been ranked by healthy lifespan. Japan, South Korea and Singapore are doing something right; that may in part be a consequence of more interventionist political system and different cultural norms around food etc. Switzerland and Norway have good stats on healthy longevity – they are also high wealth with a less marked social divide between rich and poor, and a greater emphasis on work-life balance rather than economic growth at all costs.

 

  1.              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:

 

Drug repositioning

Many drugs developed for cancer are back-catalogued by pharma at great cost (which is incorporated into the cost charged to the NHS of any successful therapy that makes it to the clinic). Re-testing of this wealth of resource is now being undertaken mainly by publicly-funded university labs and discovery institutes or with commercial partners, but UKRI research funding for screening programmes for drug repurposing is limited as such studies are not deemed ‘hypothesis driven’ hence do not meet stringent scientific criteria for grant award. Examples of success include:

 

Polypharmacy may be a major problem with adverse drug interactions causing a large number of age-related health problems, but polypharmacology (the ability of one drug to hit several different biological targets in additive or synergistic ways) may be incredibly useful in tackling multimorbidities – it is likely that mTOR inhibitors impact on targets in addition to mTOR, while metformin certainly has multiple cellular targets above its antidiabetic role. New drug screening programmes with phenotypic readouts rather than traditional target-based discovery strategies are needed.

 

One important omission in the questions asked in this document is the role of the microbiome in ageing and health. Large scale studies are starting to reveal a very complex interplay between gut bacteria and health, with implications for a range of ARDs including diabetes and dementia. Indeed, it may turn out that multimorbidity clustering may be associated with microbiome composition. Looking solely at human cells is far to anthropocentric when our bodies contain at least as many microbial as human cells. E.g. gum disease bacteria may be important in dementia – Cortexyme are developing gingipain inhibitors that are showing promise in early clinical studies.

 

 

  1.              How complete is the understanding of behavioural determinants and social determinants of health in old age, and of demographic differences?

This is outside my area of knowledge/expertise.

 

Technologies

 

5. What technologies will be needed to facilitate treatments for ageing and ageing- related diseases, and what is their current state of readiness?

Smartphone apps are now the norm for young people for monitoring health, diet and exercise; baby boomers are generally happy with technology though with privacy concerns. In the current older generation, uptake of tech is likely to be more challenging: it will need to be virtually independent of end-user input, though could be integrated with care packages, provided carers are not themselves frail elderly (and technophobic); this is unlikely to be the case.

However, the premise of using technology for monitoring lacks aspiration by accepting the status quo – that older people will get sick and that monitoring provides early intervention; while it may extend independence for a short while, it won’t prevent transition into high dependency states. We should not be content to put up with how ageing currently is in terms of biological deficit in the last few years of life – the personal and economic costs of the greying population with current ARD risk porfiles cannot be supported by the economy. We don’t need more gadgets to monitor people’s health deteriorating, we need drugs to stop that deterioration if we are really going to make a significant difference – the recently announced ‘Healthy ageing grand challenge’ has fallen directly into this trap, possibly driven by a tech-engaged DoH, and excluding biomedical research entirely from its remit – yet it aims to improve health. Treatments needed may also include advanced therapies such as gene therapy and stem cells, and drugs that target whole cells (e.g. senolytics) rather than traditional medicines that target single proteins. Small molecules can rarely achieve the ‘gain of function’ necessary for restoring deficit – synthetic compounds are usually limited to inhibiting an enzyme or stimulating/blocking a cell surface receptor. Lessons from biology, particularly premature ageing syndromes, highlight that DNA metabolism is central to health hence another critical but under-served area for drug discovery is enhancing DNA repair.

 

6. What technologies will be needed to help people to live independently for longer, with better health and wellbeing? What is the current state of readiness of these technologies, and what should be done to help older people to engage with them?

Old people struggle to adapt to new technologies, automation/autonomy is required. We reiterate: allowing people to retain their health in later life by supporting their immune systems, DNA repair pathways and other metabolic processes of cells and tissues will allow them to stay independent and avoid dependency transitions far more effectively than monitoring them as their health deteriorates. Healthy people are economically active, both as producers and consumers.

 

7. How can technology be used to improve mental health and reduce loneliness for older people?

That’s the wrong question: technology can only do so much. A face time call is good but a real person calling is even better. Societies need restructuring with much better support of community volunteer groups, with spaces and utilities provided from the public purse.

 

8. What are the barriers to the development and implementation of these various technologies and how do we overcome them?

Again, the emphasis on technology is misplaced (though driven by energetic and vocal advocates). Barriers to uptake of effective interventions and ways of overcoming them are covered to some extent in the answers above. However, I have identified key aspects which I term ‘the 4 As’:

(i) Awareness: Very few people – even in the medical profession - are even aware that new medicines exist that can positively and significantly affect health outcomes on ageing. Training of medical professionals on the scope for new medicines for ageing processes needs to start at preclinical level; ageing therapies should be in the GCSE biology curriculum, as are monoclonal antibodies and stem cells (our young people often know more than their parents and even professionals deciding their futures).

(ii) Acceptance: ageing is perceived as ‘normal’ and hence interfering in the ageing process is seen as abhorrent. However, public audiences are highly receptive to a conceptual reworking when senescent cells are equated with cancer cells – the body’s own cells going rogue, with therapies to treat/prevent that. A trusted public figurehead (as in David Attenborough on climate change and plastics) would help to educate and reassure the public and can drive political change. Media engagement is vital.

(iii) Affordability: most new drugs cost too much, but some promising senolytics are repurposed anti-cancer drugs (e.g. dasitinib, mTOR inhibitors) or natural products (e.g. fisetin, quercetin), while some immune-supportive drugs e.g. statins are already widely used and cheap within the NHS. Stem cells and gene therapies will be expensive but shared risk/cost with public-private partnerships; public-based manufacturing facilities (eg national blood transfusion service) should also help cut costs.

(iv) Application: getting drugs to the clinic needs a streamlining of clinical trials including basket and umbrella trials within the NHS (these spread risk and cost and increase hit rates). Application of other strategies across all socioeconomic sectors needs a huge shift in political will away from capitalism at all costs (i.e. form a philosophy to a process), to factor in population wellbeing and health maintenance as core economic and social goals.

 

9. To what extent do socio-economic factors affect access to, and acceptance of, scientific advice and use of technology by older people and those who care for them?

The poverty trap is covered above, including epigenetic issues that reinforce poor health. Modern culture neglects the elderly (especially sick elderly) and their isolation. “Retirement communities” may help, but fully integrated multi-generational communities make even more sense. Better education, housing and employment, with improved community structure and age-friendly infrastructure are needed – especially in deprived areas – studies in Bradford shows that user engagement can work.

 

Industrial strategy

 

  1.              What opportunities are there for industry in the development of new technologies to help increase health span? In which areas of medical research and technology development does the UK excel?

The UK is particularly strong in primary biomedical research and drug discovery – see also Bell report.

 

  1.         What more is required for the UK to benefit from commercialisation of its discoveries and inventions relating to healthy ageing, as envisioned by the Government’s Industrial Strategy?

Provide non-dilutive grants to biotech start-ups targeting fundamental mechanisms of aging and find a way to streamline tech transfer from universities, and clinical trials via NHS. Provide tax breaks for investors/pharma and clinical trials. Integrate all under a National Institute on Aging (cf US model).

Drugs don’t have to be expensive: statins improve pneumonia outcomes in acutely sick elderly people yet cost very little. Repurposed drugs and ‘me-toos’ should be developed in a public-pharma risk/cost sharing basis (eg ‘first refusal’ models of drug discovery/manufacture should be employed where primary discoveries are made in publicly funded labs but subsequently taken up by pharma), with trials hosted within the NHS; GP surgeries could serving as recruiting and sampling spokes for a clinical trial hub. Educating heath care practitioners on the reality of maintaining or even improving their patients’ health and providing financial incentives for health maintenance as well as illness treatment should minimize cost to the public purse while maximizing benefits.

 

Healthier ageing

 

11. How feasible is the Government’s aim to provide five more years of health and independence in old age by 2035? Which organisations need to be involved and who should lead?

Feasible if it is evidence-led and relies on biomedical science to improve health rather than tech to watch health deteriorate. See above for answers to strategies and policies (esp answer to Q8)

Universities, SMEs, pharma, BMA/BMC, the NHS, UKRI and Innovate UK should all be part, with financial partners including eg large pension companies as well as foresighted VCs.

The people who should lead this should be up to date on major recent advances, not dogmatic or blinkered in view and able to understand all the background at biomedical, societal and health economic levels, given a sufficient time-scale and budget in which to operate and absence of other pressures to really get on top of the brief – so probably not politicians, or individual business sectors. Including experienced senior civil servants who have broad overview of the issues would be helpful.

 

12. To what extent are inequalities in healthy ageing, as well as differences in acceptance of technologies, a barrier to achieving the aims of the Government’s Ageing Society Grand Challenge?

Very significant – it may be the same old story that the rich get more well and the poor have diminished health. Some problems are established eg at the epigenetic level prior to birth and may be passed down over several generations – the vicious cycle of deprivation is outlined above. Dealing with housing and pollution, crime, and low-wage stress, as well as poverty of aspirational and societal disillusionment will initially give bigger health dividends to the lowest socioeconomic quartiles.

 

a. To what extent could achieving the Government’s aim of five more years of healthy and independent life exacerbate, or reduce, these inequalities?

Better health reduces poverty and eventually may contribute to breaking the vicious cycle of poverty –tackling the causes of stress and inequality may be the first and most important way to improve health in lower socioeconomic groups.

 

13. What would be the implications of a paradigm shift to people leading healthier lives for longer, and spending less time suffering ill health?

Major shifts in public attitudes of the continuous lifecourse (‘The 100 year life’) that encourages healthy lifestyles but (without penalising the ill or frail), what constitutes a working life and acceptable retirement age, expectation and working patterns by employers to ensure intergenerational fairness and adapted workstyles for older people. Design adaptable full lifecourse housing suitable for a lifetime of living in the same home, encourage shared living (eg council tax breaks).

 

19 September 2019

 

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