Scientific basis

1

How complete is the scientific understanding of the biological processes of ageing and their epidemiologies?

As we age, some people age well, and others develop the clinical problems seen in adverse or unsuccessful ageing. These are the accumulation of many individual diseases – what we call multimorbidity, and a specific type of adverse ageing – frailty.

Multimorbidity is the co-existence of different health conditions, usually greater than two diagnosed diseases. Up to 1 in 2 people over 65 years will have more than 1 long term disease.

Older people with frailty represent a sub group of those with multimorbidity who are at especially high risk of experiencing adverse health outcomes. About 1 in 10 people over 65 years will have frailty, and this increases to 1 in 3 at over 85 years.

Advancing age is the most important risk factor for frailty and multimorbidity, and the fundamental biological processes driving ageing are now better understood. These include: increased DNA damage, genomic instability, reduced mitochondrial fitness, telomere shortening, reduced proteostasis and autophagy, all leading to the accumulation of senescent cells. Senescent cells are cells that have reached the end of their programmed function, but do not die. They remain, like the stand-by mode on a television, activated at a low level, and produce proteins and signals that lead to a low level of background inflammation.

However, the role these mechanisms play in causing unhealthy ageing (frailty and multimorbidity) has not been described. We believe this information is crucial for the design of clinical trials and development of novel therapeutics aimed at inhibiting ageing processes in order to reduce frailty and multimorbidity.

The University of Birmingham (UoB) and BHP are at the forefront of developing this work, through collaboration between geriatricians and discovery scientists at the (UoB) Institute of Inflammation and Ageing – we believe we are one of very few academic centres currently able to deliver this

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?

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

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

The evidence for public health advice is strong for physical activity.

The practical impediments to public health advice being acted upon include:

• lack of financial resources to pay for classes/equipment
• lack of infrastructure, for example fitness centres, or gyms that are age friendly
• the cultural view that older people are supposed to be less active – “we are meant to be sedentary when retire”
• social barriers such as solitary living and loneliness

We also note there are a lack of clinicians who work in ageing and influencers within Public Health England. This is a potential impediment in terms of not enough experts to give the practical advice about delivering interventions to the right people. This may be an area where the recently described precision public health approaches could be highly effective

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?

Treatments aimed at the underlying mechanisms of ageing may improve a range of ageing related diseases, rather than trying to treat individual diseases with different, potentially interacting, treatments. These would aim to increase health span – so to delay, or reverse, the onset of adverse ageing. Potential treatments include:

a)    Targeting senescence - Dasatinib, fisetin and quercertin (tyrosine-kinase inhibitors), or azithromycin and Roxithromycin (macrolide antibiotics that have senolytic effects, not seen in other macrolides such as erythromycin)

b)    Anti-inflammatory – Methotrexate, Ruxolitinib (JAK inhibitors), metformin (AMPkinase inhibitor)

This may involve repurposing drugs such as metformin (which increases the rate senescent and dead cells are cleared), or the development of new small molecule drugs to target specific cellular functions. Some repurposed drugs, such as dasatinib, are used as chemotherapy presently for cancer, so a key limitation is the high side effect profile – so considerations of drug safety and tolerability are important in the development of any novel compound.

Again, at UoB we are leading on trial design and submitting funding for the first clinical trials with these agents.

Comprehensive Geriatric Assessment (CGA) is a term which encompasses a multidisciplinary assessment (by geriatricians, physical and occupational therapists, pharmacists, etc.) of older people to identify treatable conditions, and reduce the risks associated with frailty (falls, fractures, delirium). We know CGA works; to reduce the time people spend in hospitals, and increase their chances of being alive, and living in their own home.

However, the broader application of CGA outside of hospital settings is not known, and this is hampered by the resource requirement to deliver it – we need more geriatricians, and more therapists trained to deliver CGA – however, once in place, it is a cheap intervention.

Given CGA is a limited resource, then using personalised approached may help to identify those who will benefit most.

A greater understanding of how interventions such as physical and cognitive exercise and social interactions prolong function could help focus interventions more accurately and suggest new therapeutic targets.

Through our collaborative BHP approach, we have developed a data solution using data collected routinely when a person is admitted to hospital. This is used to derive a ‘Frailty Index’ which predicts those at greatest risk of dying, or going into a care home. The next step is to test this in a trial that tests if directing CGA to those identified as high risk, improves the person’s outcomes.

Technologies

5

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

We believe the following technologies will facilitate effective monitoring:

a)    Tech enhanced adult incontinence products – able to evaluate level of hydration/metabolites in urine/faeces

b)    Robotics and robotic care assistants

c)     Smart devices that are adapted for digitally naïve older people

d)    Upgrade home environments with minimally intrusive forms of monitoring

e)    Mobility devices e.g. cars that can monitor and evaluate behaviours/health on the move.

f)      Video link support to care home staff and ambulance services to expert geriatric medicine practitioners, to manage risks associated with hospital admissions

These are all technologies currently being explored by BHP. The Birmingham and Solihull Sustainable Transformation Plan (STP) is currently leading on this community/hospital interface work with clinician leaders from BHP.

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?

The following Smart technologies may allow people to live independently for longer:

a)    Robotics and robotic care assistants

b)    ‘Smart homes’ that include technology to identify people at risk of illness,

8

What are the barriers to the development and implementation of these various technologies (considered in questions 5-7)?

a. What is needed to help overcome these barriers?

b. 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 withdrawal of ageing programmes by big pharma because they are perceived as too complex and high risk. A lack of accepted and robust end points to test interventions against.

Most importantly however is the lack of research capacity in terms of personnel and lack of specific funding opportunities in the ageing space. This is true for most of our responses.

A key knowledge gap is that we do not know socio-economic factors that affect access to, and acceptance of, scientific advice and use of technology by older people and those who care for them. This is the same with health innovations as well – this requires investment into dissemination, but also seeing greater patient and public involvement in research that addresses at risk groups of older people, where it currently involves mainly ‘well older adults’ who may have different needs – this is difficult however.

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 key opportunity and growth area is in senolytic drugs, defining the question we want to answer is key i.e. living longer and healthier.

We believe the UK excels in the following areas:

a)    Strengths in the pharmaceutical industry

b)    Strengths in public health, but poor connection to manufacturers of devices that might facilitate healthy interventions.

c)     Strengths in virtual environments/computing which might enhance cognitive training.

d)    Strengths in design to allow products to work better with intended target audience.

e)    Strengths in material sciences/manufacturing to develop smart wearable clothing that can help movement etc.

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?

We believe we need more clarity over pathway from product innovation to market, evergreen capital to facilitate company growth, better cross sector collaboration, clarity over evidence base needed for regulatory approval and adoption with NHS/Social care.

However there is a need for strategic clarity in terms of what Pharma is trying to do in the ageing space – targeting ageing mechanisms, as discussed above, is one such strategy, but Pharma may need to change structurally to be more effective when tackling complex multisystem problems.

Healthier Ageing

11

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

a. What strategies will be needed to achieve the Government’s aim?

b. What policies would be required, and what are their potential costs and benefits?

c. Which organisations need to be involved?

d. Who should lead the work?

The Government’s aim will need to be multidisciplinary and break down current siloed thinking. Multidisciplinary partners must work together to design and commission, with outcomes that are meaningful to the organisation and the population accessing the services.

There is a significant need to increase capacity across ageing research, but especially in the medical discipline. To provide five more years requires both 1) prevention strategies – which may need implementation across the life course, and 2) better diagnosis and treatment of age related conditions when they develop.

We believe the following strategies will help realise the aims: Active capacity building, development of multidisciplinary research centres, or multi-organisational consortiums would have a significant effect. The National Institute of Ageing in the ASU is a good exemplar.

High quality ageing research, by its nature, is cross specialty, but there has been a distinct lack of clinicians, and more specifically geriatrician involvement in policy development. The needs of older people need to be heavily involved, as well, through public involvement schemes.

There is a need for leaders who are comfortable working across universities industry and the NHS and PHE to deliver this.

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?

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

There is a key association between lower socio-economic status and frailty – so older people who live in these areas are more likely to age unsuccessfully. This is a major health inequality and barrier to delivering the Government’s Grand Challenge.

There are risks around healthy ageing strategies, especially lifestyle strategies, being time and money dependent – so paradoxically, those who may benefit the most from interventions will be less able to access them.

The Birmingham and Solihull STP, led with BHP clinicians, has recently done a piece of work to map what facilities and 3rd sector projects are available in different neighbourhoods across Birmingham – and importantly how that matches the needs of the population. This allows the social determinants of health to be addressed on a local population level – for example Harborne ward (affluent) and Weoley Castle ward (deprived) are very close geographically, but with very different needs.

13

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

• Economic impacts

• Time spent in work as opposed to in retirement

• Provision of activities and services for active older people

This is known as maximising the ageing dividend.

UoB has been involved in major work here with respect to adult social care (which we know is not in the remit of inquiry). However, these principles are important in all ageing health settings

Investment in improving the health of older people should be seen as a form of economic and social investment – as it will lead to savings in the NHS and in social security, as well as extra tax/NI revenue (e.g. if more people caring for family members were able to combine work and caring, then there would be a reduction in social security payments and more tax/NI income etc.).

The majority of evidence based healthcare interventions for frailty and multimorbidity -Comprehensive Geriatrics Assessment (CGA), and delirium prevention strategies, for example – have been shown to be cost effective once implemented by reducing hospital bed days, and reducing the need for longer term support in the community.