Babraham Institute – Written evidence (INQ0070)
The Babraham Institute is a BBSRC funded life sciences research institute located on the Babraham Research Campus on the outskirts of Cambridge. The Babraham Institute undertakes world-leading research into understanding how our bodies work, including what changes as we ages and during disease. Our research focusses upon cell signalling, epigenetics and immunology and in addition to making fundamental discoveries we aim to ensure translation of our findings for the benefit of society.
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.)?
The scientific understanding of the biological processes of ageing is far from complete. We still lack a basic understanding of why organisms age. There has however, been a notable and encouraging increase in solid molecular experiments. These have led to a greater understanding of the molecular basis of ageing, including the identification of genes and epigenetic factors with roles in ageing. There is, however, a lack of knowledge about why these molecular changes occur in such a reproducible manner in all individuals. We also do not understand yet, why the process of ageing is conserved across species including flies, worms and mice as well as humans. This coupled with the fact that the mechanistic impact of environmental factors is significantly less clear means we are still far from a detailed understanding of the complete underlying biology of ageing.
Although genes and polymorphisms associated with longevity and ageing health have been identified, in most cases we have little understanding of why particular genetic changes have particular outcomes. Definition of the epigenetic clock of ageing in both mouse and human systems is providing an insight but we need a more detailed understanding of its mechanism and how its changes are translated particularly into effects upon health span rather than longevity.
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?
The majority of advice is basic public health advice (eat well, don’t smoke, exercise) etc. These certainly act to reduce the risk of contracting various diseases for which ageing is a key risk factor (cardiovascular disease, diabetes, cancer). It is not at all clear that these lifestyle changes actually impact the underlying ageing process, despite increasing evidence that these can induce epigenetic change. The scientific basis for public health advice improving health is good, for improving healthy ageing it is shakier. The important point here is that improving health in youth and middle age does not necessarily result in less debilitating disease in later life – paradoxically by removing causes of earlier mortality, healthy lifestyle advice may actually increase the proportion of the population suffering extended debilitating conditions at the end of life. Nevertheless, there is evidence from mouse studies that the detrimental effects of an obesogenic diet in the young is poorly reversible in older animals, clearly pointing to the importance of addressing childhood obesity.
In addition to the existing unwillingness to respond to health-related messages in certain communities, this probably requires a massive epidemiological effort to correlate late-in-life health to widely varying aspects of lifestyle. In order for this to be the most effective it would need a multi-disciplinary approach. Preferably linked to molecular analysis of current and historical patient samples measuring eg: transcriptome, epigenetic clock, etc. This would be a vast undertaking.
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: • Treatments based on new approaches e.g. senolytics, epigenetic therapy • Drug repositioning • Treatment of co-morbidities and polypharmacy • Diagnostics, particularly early diagnostics for ageing-related diseases • Biomarkers for diagnostics and for monitoring effectiveness of treatments • Personalised medicine for ageing-related diseases and multi-morbidities
It is known that vaccination efficacy declines significantly with age, recent studies are elucidating the mechanisms underlying this. Included in this work has been the recognition that adjuvant variation can increase responses in older subjects this may lead to improved vaccination leading to improved health of the elderly.
Otherwise short-term effects upon healthspan are unlikely. Although each of these has potential, there are massive problems inherent in treating ageing as a druggable disorder. For example, how do you run a clinical trial on ageing? Clinical trials generally last 5 years and it is hard to imagine that a significant positive outcome would emerge in this timeframe. Polypharmacy against a single condition is practically challenging due to treatment regimens needing to be optimised, and in a situation where multiple drugs against multiple morbidities are being assessed in already frail patients the likelihood of positive outcome appears low. Early biomarkers will be useful if and when we have credible drugs or lifestyle interventions to treat age-related pathology. That said recent trials of senolytic drugs in patients with diabetes-related kidney disease have been promising, though until repeated with a larger sample size the data must be treated with caution. Similarly epigenetic therapy has shown effects in mice but such approaches remain untested in humans.
4. How complete is the understanding of behavioural determinants and social determinants of health in old age, and of demographic differences?
Demographic data from government agencies clearly points to a disparity in healthspan between the wealthier and poorer regions. Much of this tends to be a bit superficial and doesn’t properly investigate lifestyle factors.
5. What technologies will be needed to facilitate treatments for ageing and ageing-related diseases, and what is their current state of readiness? For example: • Drug delivery devices, for existing or future treatments • Technologies for monitoring conditions and providing personalised medical advice • Technologies for monitoring healthy living e.g. fitness, diet, etc.
Advanced techniques to measure the epigenome such as single cell multiomics will allow simultaneous measurement of genome, epigenome and transcriptome in individual cells. This in turn will allow identification of cellular heterogeneity; some of our cells may have genetic, epigenetic or trancriptomic signatures that mean they are more likely to age and senesce earlier than others; some may have signatures that mean they are more likely to progress to disorders such as cancer. Consequently, this information can be used to personalise health advice or treatment. It may also identify those who will age well and those who will not and those who may benefit from dietary interventions to prolong healthspan.
8. What are the barriers to the development and implementation of these various technologies (considered in questions 5-7)?
It is clear the capacity to conduct experiments with much higher throughput will be necessary to answer some of the key questions around understanding and improving health as people age. Additionally, the cost of doing such work will need to be reduced in order for these types of experiments to be feasible. Such work will need to take into account multiple dimensions and disciplines, including, but not limited to, the genome, epigenome and proteome. This multi-disciplinary approach needs also to take into consideration time as a factor, these studies need to take place over a much longer time scale.
It is clear that these experimental approaches will generate large amounts of data. Therefore it is also crucial that significant investment is made in the computation and data storage required to effectively deal with this big data.
9. 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 excels in basic biomedical research which will increase understanding of healthspan, in particular in immunology and epigenetics. Understanding of senescence is also an area of considerable expertise in the UK. There are unexploited opportunities for industry to link with academia to exploit these developments.
10. 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?
Partnership working will be critical to identify and develop potential drug targets. However it will also be necessary to develop a strategy in collaboration with industry for developing a clinical trial framework that is suitable for ageing, otherwise drug pipelines will not be developed. A practical (though different) example of this is the efforts being made to develop new reward strategies to make the development of new antibiotics more attractive without them being over-priced or over-used.
11. How feasible is the Government’s aim to provide five more years of health and independence in old age by 2035?
The integration of research findings, commercial exploitation and healthcare benefits will require policy and practice changes to bring together the relevant policy makers from BEIS and DH. As mentioned above, a multi-disciplinary approach that brings together expertise in all relevant areas from basic science up to patient care will be needed to achieve the Government’s aim.
20 September 2019