List of questions
What are the possible routes, best ways to engage with doctors and particularly since we are talking about the UK, with the NHS? What are the possible routes to participate in aging focused clinical trials?
Biological aging is not recognised as a disease, with good reason, the tests are non-diagnostic, non-clinical and without involvement of physicians the outcome that can be provided is very limited. I call it zeronary care for end users that comes before primary or secondary care. What are the possible routes, best ways to engage with doctors and particularly since we are talking about the UK, with the NHS? What are the possible routes to participate in aging focused clinical trials?
Which mechanisms or 'hallmarks' of aging are the most under-appreciated for drug discovery? What is the 'low hanging fruit' for clinical translation?
These are the classic hallmarks, but it's not a complete list: https://www.cell.com/abstract/S0092-8674(13)00645-4 If you needed to develop a drug to slow down aging, what targets or mechanisms would you pursue? Extra bonus points for originality! This is not just a theoretical question -- if you have a really great idea, Apollo will fund your research / spinout.
Do you think that therapeutic interventions that target mechanisms of aging can be developed to reduce disability in aging outside treatment of specific disease, and if so what targets/mechanisms and what development pathways are most promising?
In the last decade, it has been shown in small animals that interventions to block or reverse some of the underlying biology of aging can have substantial effects on the disabilities of aging. Autophagy-inducers (or caloric-restriction mimetics) such as rapalogues, telomere extension agents, and senolytic drugs have been shown to reduce age-associated disabilities in a wide range of mouse models. This type of intervention can be applied in a traditional 'drug discovery' mode to develop treatments for specific diseases (e.g. development of UBX0101 for osteoarthritis). But such development presumes that you are treating a specific disease, not the wider disabilities of old age. Can they be developed for treatment of more general disabilities of aging, such as pre-dementia cognitive decline, sarcopenia, skin thinning and fragility, 'frailty'. If so a) what are the most promising targets, mechanisms or dysregulations that could be deployed in this way, and b) how can such products be approved in the absence of a classic ICD disease to treat?
What new, effective, large-scale government intervention can we suggest to support UK companies developing Healthy Ageing & Rejuvenation Biotechnology?
The healthy life expectancy goals set by the Government are the bare minimum to make the news, 5 years increase in healthy life expectancy still puts UK below several European countries.The current policy has little to do with intrinsic ageing; it just addresses extrinsic ageing (cut the carbs, exercise etc) and symptamotology. The UK was at the forefront of the biotechnology industry in the era of 'conventional' biotechnology drug discovery and development from 1980 - 2000. It is still a global leader in research, but almost none of this is being translated into development or deployment. We are at a cross-roads; we can continue to do world-class research in ageing and see the results commercialized and deployed in California or China, or we can take action. But what action is both valuable and do-able?
What is the impact of baseline immune status (‘inflammaging’) on the age effect of immune responses to vaccines and infections?
Aged-related chronic inflammation, defined as “inflammaging”, negatively affects the immune responses and is associated with health defects (Fulop et al, Sem Imm 2018). Inflammaging is a complex phenomenon which include soluble factors (e.g. IL-6, IL-1, C-reactive protein), activation of monocytes, and intracellular danger-sensing complexes such as inflammasomes (e.g. NLRP3, NLRC4) (Latz & Duewell, Sem Imm 2018). Inflammaging is associated with epigenetic changes and some of the epigenetic clocks that describe biological age comprise inflammation and interferon pathways. The root causes of inflammaging may be driven by changes in the microbiome, age-related co-morbidities, chronic infections, dietary regimens and/or by changes in BMI that occur with age. Acute and/or chronic stress can also affect immune system regulation. Finally, because of their first-line defense role, innate immune responses may be increased because they compensate for decreased adaptive immunity making increased baseline innate activation the result, rather than the cause, of decreased adaptive responses. Targeting inflammatory pathways by adjuvant/drug might be a way to overcome age-related-inflammaging. Hence, combining vaccination with a rapamycin analog targeting the mTOR pathway provided an early proof-of-concept (Mannick et al, S Transl Med 2014).
Is there an epigenetic basis for immune response differences that can explain discrepancies between biological and chronological age?
Immunosenescence is defined as the cumulative changes in the immune system that occur over time and that affect immune system responsiveness. The underlying mechanisms are multifaceted and are associated with functional changes in immune cells. These changes are at least in part epigenetically regulated. A key concept is that the biological age of the immune system is not linearly related to chronological age. Recent work has shown that epigenetic clocks described by CpG methylation data, is able to accurately estimate biological in comparison to chronological age (Horvath & Raj 2018). Many factors, including environmental, lifestyle and epigenetic factors can accelerate or decelerate immune system aging. A second more powerful DNAm-based estimators of biological age that incorporate physiological parameters reffered as DNAm PhenoAge was recently described by Morgan Levine and outperformed the first generation of DNAm age estimators for predicting mortality, heath span or cardiovascular disease and showed a strong relationship with various measure of multi-morbidity. Epigenetic clocks link developmental and maintenance processes to biological aging but their relationship to immunosenescence and impaired responses to vaccination has not been studied yet.
How could we use machine learning to develop an intelligent gyroscope glove for 200M people globally with hand tremors (Parkinson’s disease, essential tremor)?
GyroGear is developing intelligent gloves to restore independence and quality of life for 200M people globally with hand tremors (Parkinson’s, Essential Tremor). The gloves currently feature a high-performance mechanical gyroscope coupled to the back of the user’s hand. We seek to develop: • Intelligent tremor and identification systems • Complementary machine learning capabilities for 1) control of the GyroGlove and 2) long-term physiotherapy and rehabilitation applications • Clinical partnerships for testing and R&D Future platforms: • Long-term tremor and movement disorder tracking in community (e.g. stroke, tremors, neuropathies, multiple sclerosis etc) • Rehabilitation, physiotherapy • Post-surgery rehabilitation (e.g. orthopaedics) Introduction to our project (BBC One Show) - https://vimeo.com/269487349/fc7ef6c621 Performance of Jan 2019 prototype - Severe bilateral hand tremor individual. Multiple, sequential activities (to fatigue user): https://vimeo.com/330355695/30e5070965 We would like to consult and partner experts in the following areas. Experts in other relevant areas are most welcome: • Machine learning, data science • Mechatronics • Gyroscopes • High performance electrical motors • Movement Disorders • Neurology, neurological engineering • Orthopaedics • Geriatrics • Physiotherapy, rehabilitation • Digital health
As a product that aims to have a positive impact at the beginning and middle of a given person’s journey with dementia, a degenerative condition, how can we best measure impact and success?
How Do I? links video content to objects in peoples’ homes and workplaces. Using our app, people affected by dementia and their carers can record personalised video content. Then, they can link that video to a bright and easily-identifiable contactless sticker. The video can be accessed from the touch of a mobile device on to the sticker. People can create step-by-step content related to daily routines like cooking. Or they can use the app like a video diary, recording snippets of their day to day activities and linking the content to a calendar at home. Our users have reported that they really enjoy seeing the content back, and that video helps remind them of where they’ve been, what they’d been doing and who they’d been with. We believe digital solutions are key in helping improve care and quality of life for people affected by dementia now and in the future. We hope that by implementing technology like ours at an earlier stage of someone’s dementia journey, we can help them live independently for longer, while feeling happier and more connected to their loved ones and community. We are currently working in partnership with the Alzheimer’s Society through their Innovation Accelerator. As a product that aims to have a positive impact at the beginning and middle of a given person’s journey with dementia, a degenerative condition, how can we best measure impact and success? With our technology, we are aiming extend the length of time a given individual is able to feel connected and confident through small, incremental experiences early in their journey with dementia. It is highly likely that over time, users will experience a decline in their capacity with or without our technology, and many factors will impact how this progresses for each person. As a small startup without the resource to undertake large scale academic testing, where do we begin?
Is there enough data obtained from wearable technology or similar self-monitoring devices to help people understand the physiology of ageing and to effectively advise individuals of how to make best use of this information?
Wearable technology offers a way of continuously and unobtrusively monitoring various physiological parameters and vital signs while individuals go about their normal daily lives. There is a fairly widespread belief that this is “somehow” very valuable and “we” (or rather “they” – the aging) should all be doing it. The technology is invariably connected to the “cloud” via the internet. The technology is also capable of collecting a large amount of data relating to individuals and populations.
What are the benefits of monitoring ADL (activities of daily living) during reablement and how could they be measured?
Kemuri has developed technology designed for accelerating discharge from hospital and continuously monitoring activities of daily living (ADL) during the reablement period. The objective is to ensure that the risk of re-admission is reduced and that people are provided with appropriate levels of care in their own homes. Reablement is free of charge to service users (Care Act 2014). Trials have successfully proven the technology in several locations. The issue is providing evidence of value from an academic quality review. A full-scale trial requires a joint project of a hospital trust and a local authority responsible for the reablement process. It would answer such questions as: - How many excess bed days can be saved in hospital before discharge? - What is the probability of avoiding readmissions? - What proportion of nursing and domiciliary care can be saved? - What is the projected return on investment? - What processes are recommended for assessment and responding to sensor readings and alerts? The purpose for attending the Academic Industry Meeting Day is to raise awareness of the technology and attract possible partners for a funding bid.
How could medication adherence be improved using tech and how could the data produced inform future protocols and/or design? What are the potential issues that arise regarding confidentiality?
Poor medication adherence by some older adults, is a well-recognised problem identified by both pharmacists and doctors. This is particularly a problem in cases where there are complex medication regimes and/or cognitive impairment. Blister packs are designed to counteract some of this issue but still rely on patients themselves adhering to the regimen, and provide no feedback to other stakeholders (families, doctors, pharmacists etc.) on whether medication is taken correctly. There are some ‘smart’ pill boxes on the market, however there is little evidence that these provide optimal feedback to relevant parties. The Link-ages system is designed to facilitate safe, easy and private communication between older people and their families (and in future, professional parties like care providers or medical professionals). Our aim is that, using carefully designed technology, we can improve the lives of older adults, regardless of their tech experience and skills. Questions arising: • What is the threshold for obtaining blister packs? • Could a blister pack, filled by a pharmacist, be integrated into a low-cost smart pill design that provides feedback on adherence? • If third parties (pharmacists, doctors or family members) are able to access information regarding adherence, what confidentiality problems would need to be addressed? • If this system was to be run using the Link-ages platform to involve both professionals and family members, what protections would need to be in place regarding data privacy etc.? • What potential barriers would there be to integrating this type of smart tech into health records?
How could tech be used during hospital stays and in residential care (and during transition) to help staff, reduce stress for patients and families, and improve outcomes? How is technology currently used in care (domestic and residential) settings? What would improve staff workload and patient outcomes?
Moving from independent living into hospital or care can be hugely stressful for patients and their families. Furthermore, geographical isolation from family and friends can reduce wellbeing, even while medical and other needs are being met. Our research with care homes has demonstrated that managers are keen to provide ways for residents to stay more connected with their families, and we are currently looking to build a care based addition to our platforms that would enable residents and carers to communicate with residents and family members easily and safely. We are keen that this system should also be beneficial to care providers, allowing them to carry out their roles more easily. Questions arising: • How could tech-based solutions help staff to carry out their roles more effectively? • If tech was used to connect residents and staff, what safeguards would need to be built in to ensure that residents were still physically checked regularly (i.e. tech was not used to reduce contact), but staff and residents could use digital communication for ‘routine’ messages etc.? • Could this type of technology help residents to share memories etc. with each other? What facilities would need to be available? How could we embed this system? • Could this system, that enables sharing of memories, help patients with cognitive impairment to share with staff and other residents, stimulating conversation and helping to alleviate loneliness and isolation? • Could machine learning be used to track engagement with this technology to help identify declining mood, function, etc.? • How could technology be used in such a way that independence is retained for longer, and how could it be used to improve the integration of domiciliary care? • Would a more tailored introduction of technology to older adults improve take up? For example, if the first introduction to tech is because it is ‘essential’ does this negatively impact the use of assistive technology?
What new tools and technologies hold the most promise for expanding our knowledge of celullar aging?
A finite number of ageing ‘hallmarks’ have been defined, but how these hallmarks interact over time to drive aging remains undefined. Moreover, the hallmarks might simply represent a partial understanding of ageing constrained by low throughput experimental methods. The advent of high throughput methods to interrogate cellular aging (CRISPR) and quantify cellular aging (aging clocks) provides a great opportunity to address both questions, but whether such methods can be implemented to generate useful data is subject to debate (which I gladly invite).
Which inpatients are most likely to receive clinical benefit by a drug that can prevent acute muscle weakness during hospitalization? What endpoints are most suitable and feasible for a new drug approval ?
Sarcopenia is associated with worse outcome such as fall, fracture and mobility disability, however the goal of treatment and the therapeutic intervention timing are yet to be debated. The European Working Group on Sarcopenia in Older People (EWGSOP2) have newly identified a subcategory of sarcopenia, acute sarcopenia, that has developed within 6 months. Evidence suggests that hospital admission due to acute injury/illness increases the incidence of sarcopenia as it is often associated with catabolic status such as bed rest, fasting and inflammation. Moreover, since sarcopenia itself is a risk factor for hospitalization, we believe that pharmacological intervention at hospital admission might be an optical point to achieve better outcome. Despite this, the prognosis and the outcome of acute sarcopenia is poorly understood. Further, they may vary among patients with different background diseases such as pneumonia, hip fracture and acute exacerbation of COPD. How could we know which patients be worth treating sarcopenia beyond treatment of specific background disease?
How can we use data from lifestyle type applications (such as Fitbit) to help the wellbeing of people suffering from chronic conditions?
In society we are creating more data than we have ever created before. Data analytics, machine learning and artificial intelligence are enabling us to analyse a big volume of data quickly and give us previously undetected scientific insight. For example this link shows how AI is being used to predict breast cancer up to 5 years in advance http://news.mit.edu/2019/using-ai-predict-breast-cancer-and-personalize-care-0507 A paper in Nature in 2018 estimated that there were over 300,000 health apps available addressing issues such as obesity, diabetes and mental health. More and more people are wanting to take control and be engage in their own health through technology. How can we use science and technology to do this in a way seamless way for the patient or consumer allowing them to leave healthier and happier lives for longer?