AGEing and NuTrition Sensing (AGENT)
Lead Research Organisation:
Imperial College London
Department Name: Metabolism, Digestion and Reproduction
Abstract
While it is known that age has a profound effect on metabolism, there is no real understanding about why some people metabolically age at a faster rate than others. A number of hypotheses exist to explain how nutrition and ageing impacts metabolism to effect ageing. Studies in model organisms have shown that nutrition and the systems used to sense the nutritional environment play a role in ageing and several genes and pathways have been identified that are associated with greater lifespan. The proposed network will focus on nutrient sensing and the role it plays in the ageing process, we aim to address the priority area of "healthspan and quality of life in old age". To address the current gaps in knowledge and to develop deeper mechanistic and translational understanding in the area of nutrient sensing and ageing, we have brought together five university partners that are Imperial College London, Newcastle, Bristol, Manchester and Edinburgh, all of which have a track record in either nutrition, nutrient sensing and ageing. Although each University has a lead CoI, they bring with them many specialities and networks based in their institution, which are both established and new to the area of nutrition sensing and ageing. This has given us a highly multidisciplinary start to the network that spans fundamental cell biology through to policy making. The network will use hackathon methodology (a methodology which we have used successfully in other networks) to develop multidisciplinary research topics which the network will support to develop into full grant application and contribute to the scientific literature. The network will have an open-door policy to welcoming new members into the network. We will also develop an early career network to ensure capacity development. As a major aim of the network is to develop new ideas for research application we believe that this will give the network life far outside of the funding period.
Technical Summary
Lifestyle and particularly nutrition has profound effect on ageing. Although it is known that aging has an effect on metabolism, there is no real understanding about why some people metabolically age at a faster rate than others. A number of hypotheses exist to explain how nutrition and ageing impacts metabolism to effect ageing. However, there are still major gaps in our knowledge. For example, food insecurity and shortage, which is associated with accelerated deterioration in healthspan, is a situation in which nutrient sensing becomes aberrant, paradoxically, food insecure people are in fact more likely to be obese, which severely impacts health span. Our proposal directly addresses the challenge area of the call "health span and quality of life in old age" it does this by bringing together a multidisciplinary network of scientist that have not worked together previously to focus on nutrient sensing and ageing. The network will cut across a wide number of disciplines. From nutrition to cellular biology and human physiology to population health. To address the current gaps in knowledge and to develop deeper mechanistic and translational understanding in the area of nutrient sensing and ageing, we have brought together five university partners that are Imperial College London, Newcastle, Bristol, Manchester and Edinburgh, all of which have a track record in either nutrition, nutrient sensing and ageing. Although each University has a lead CoI, they bring with them many specialities and networks based in their institution, which are both established and new to the area of nutrition sensing as ageing. This has given us a highly multidisciplinary start to the network that goes form fundamental cell biology to policy making. The network will use hackathon methodology (we have used successfully in other networks) to develop multidisciplinary research topics which the network will support to develop into full grant applications and papers.
Organisations
- Imperial College London (Lead Research Organisation)
- Medical Research Council (Co-funder)
- PepsiCo (Collaboration)
- University College London (Collaboration)
- Quadram Institute Bioscience (Collaboration)
- UNIVERSITY OF NOTTINGHAM (Collaboration)
- UNIVERSITY OF READING (Collaboration)
- University of Surrey (Collaboration)
- Newcastle University (Collaboration)
- UNIVERSITY OF OXFORD (Collaboration)
- UNIVERSITY OF GLASGOW (Collaboration)
- University of Bristol (Collaboration)
- KING'S COLLEGE LONDON (Collaboration)
Description | The development of four projects that span the work of the network Project 1: Understanding and influencing the mechanisms of ageing through dietary interventions. Aims to bring a better understanding to the interplay between genetic polymorphisms in nutrient sensing genes and dietary intake. This will help identify potential strategies to improve the ageing trajectory and health span. The project will be conducted in two stages. A modified Delphi technique will first be utilised to gain an expert consensus on the best biomarkers for ageing (current and future). An expert panel will rank possible biomarkers until a consensus of agreement is obtained. The Delphi stage of the study will be funded by the network and will bring new insights into the biomarkers of ageing. The second stage will investigate the effect of food insecurity and time restricted eating on the biomarkers of ageing identified in stage 1. Food insecurity indicates limited or unreliable access to nutritious food and can result in variability between food quality and food intake. Time restricted eating is a dietary pattern that limits food consumption to a certain time period. Both dietary patterns are characterised by periods of fasting but it is hypothesised that these eating patterns will have opposing effects on the ageing trajectory. We hypothesis that experimentally induced food insecurity may accelerate the ageing process by compromising nutrient sensing/metabolic pathways while time restricted eating may reflect a decelerated model of ageing. The study will provide a better understanding of the social and dietary factors impacting the ageing process while unravelling aspects of the mechanism behind it. Funding for this project will be sought from another source but will be strengthened by AGENTs funding and preliminary data collection Project 2: Gene polymorphisms and mechanistic understanding of impact of nutrition on healthy ageing. This aims to understand the impact of nutrition and genetic polymorphisms on healthy ageing. Nutrition is an important factor that is known to impact the ageing process and the risk of morbidity. However, the response to nutrition differs greatly between people. We hypothesize that this heterogeneity in response to dietary factors is due to polymorphisms in nutrient sensing genes. This project will have three stages. The first stage will include a short review of the area to identify candidate genes implicated in nutrient sensing pathways. The second stage will use access to big data sets (e.g., UK BioBank) to investigate the relationship between the polymorphisms in the candidate genes identified in stage 1 and ageing related factors available such as BMI, body composition, cognition and muscle strength/frailty. These two stages will be funded and supported by the network. These will bring new insights into the relationship between nutrient sensing, polymorphisms of these pathways and ageing parameters. The third stage of the study will involve mechanistic investigation of nutrient sensing pathways: cell and animal models, impact of polymorphisms on gastrointestinal and neuronal functions and potentially a human study looking into physiology. Funding for this project will be sought from another source but will be strengthened by AGENTS funding and preliminary data collection. Project 3: Understanding the Biological Mechanism and Societal Determinants of Anorexia of Ageing Many older people consume too little food due to anorexia of ageing and this contribute to the development of many age-related problems including sarcopenia. This project aims to focus on understanding the biological mechanism and societal determinants of anorexia of ageing. The project will aim to address the consensus on the definition of anorexia of ageing. Following this, the study will include two stages. The stage 1 will aim to collect preliminary data by using tissues from older adults and testing these on gut on a chip model. Stage 2 will include a review on the social aspects surrounding the anorexia of ageing such as food insecurity. Both stages will be supported by network funding and will bring new understanding regarding the mechanism as well as the social aspects impacting anorexia of ageing. Project 4: Exploring the impact of protein quality and fibre on gut barrier function, inflammation, and body composition A decline in gastrointestinal tract (GIT) barrier function is associated with inflammation and inflammation is a major driver that has a negative effect on muscle mass. Decline in GIT barrier function and low-grade inflammation are associated with ageing in animal models but robust data in humans is lacking. Dietary protein and dietary fibre have been demonstrated to have an impact on GIT integrity. The aims of this project are to explore the impact of protein quality and dietary fibre on gut barrier function, inflammation, body composition and muscle function. The project will have three stages. This project firstly aims to collaborate with industry partners to develop biomarkers of biological age and gut barrier function. Secondly, to engage with the public to develop an understanding of acceptability of changes to protein sources (e.g. legume vs. animal based protein), Thirdly to bring together preliminary data with public and stakeholder engagement to co-create a randomised control trial to test the effect of alternative sustainable protein sources and increased dietary fibre on age-related health outcomes. |
Exploitation Route | We are applying for futher funding |
Sectors | Agriculture Food and Drink |
Description | Yes we have formed two industrial partnership |
First Year Of Impact | 2022 |
Sector | Healthcare |
Impact Types | Societal |
Description | Enhanced tools to understand nutrient sensing across the life span |
Amount | £100,000 (GBP) |
Funding ID | BB/X017869/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2023 |
End | 10/2023 |
Description | Enhanced tools to understand nutrient sensing across the life span |
Amount | £100,000 (GBP) |
Organisation | Imperial College London |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2023 |
End | 01/2024 |
Title | Screen for Anorxia of Aging |
Description | This tool has been invented by Dr Holliway a CoI in AGENT. It is a laboritory assessment of appetite in older people. It assess the volunteers nutritiona intake at a meal given in excess |
Type Of Material | Biological samples |
Year Produced | 2024 |
Provided To Others? | Yes |
Impact | To early to say |
Description | Agents |
Organisation | King's College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I facilitate the partnership |
Collaborator Contribution | They have help to complete the work tasks in the paprtnership |
Impact | I is too early to list outputs |
Start Year | 2022 |
Description | Agents |
Organisation | Newcastle University |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I facilitate the partnership |
Collaborator Contribution | They have help to complete the work tasks in the paprtnership |
Impact | I is too early to list outputs |
Start Year | 2022 |
Description | Agents |
Organisation | University of Bristol |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I facilitate the partnership |
Collaborator Contribution | They have help to complete the work tasks in the paprtnership |
Impact | I is too early to list outputs |
Start Year | 2022 |
Description | Agents |
Organisation | University of Glasgow |
Department | NERC SUERC CIAF Cosmogenic Isotope Analysis Facility |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I facilitate the partnership |
Collaborator Contribution | They have help to complete the work tasks in the paprtnership |
Impact | I is too early to list outputs |
Start Year | 2022 |
Description | Blast |
Organisation | University of Oxford |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Expertise in nutrition |
Collaborator Contribution | Expertise in immunology |
Impact | We contribute to the aging network infrastructure. |
Start Year | 2023 |
Description | Carina |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We bring nutritional experise to the network |
Collaborator Contribution | Carina brings immunology expertise to the AGENTS network |
Impact | Too early at the present time |
Start Year | 2023 |
Description | Food for Years |
Organisation | University of Reading |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have collaberated in the field of food, nutrition and aging |
Collaborator Contribution | The partners bring expertise in eating behaviour in older people |
Impact | We have agreed to collaberate on the joint funded project |
Start Year | 2023 |
Description | Food, Microbiome and Health Partnershipn |
Organisation | Quadram Institute Bioscience |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We bring interventional human research to the partnership |
Collaborator Contribution | They bring scientific experises |
Impact | Too early in the partnership for outocmes |
Start Year | 2023 |
Description | Food, Microbiome and Health Partnershipn |
Organisation | University of Nottingham |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We bring interventional human research to the partnership |
Collaborator Contribution | They bring scientific experises |
Impact | Too early in the partnership for outocmes |
Start Year | 2023 |
Description | Food, Microbiome and Health Partnershipn |
Organisation | University of Oxford |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We bring interventional human research to the partnership |
Collaborator Contribution | They bring scientific experises |
Impact | Too early in the partnership for outocmes |
Start Year | 2023 |
Description | Ripen Management Committee |
Organisation | PepsiCo |
Department | PepsiCo, UK |
Country | United Kingdom |
Sector | Private |
PI Contribution | Imperial College Host the hub so provide all organisational input |
Collaborator Contribution | They contribute expertise and advice |
Impact | We have run the priority setting for the hub. We have awarded two rounds of funding |
Start Year | 2023 |
Description | Ripen Management Committee |
Organisation | University of Surrey |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Imperial College Host the hub so provide all organisational input |
Collaborator Contribution | They contribute expertise and advice |
Impact | We have run the priority setting for the hub. We have awarded two rounds of funding |
Start Year | 2023 |
Description | Stable Isotope and Short Chain Fatty Acid Partnership |
Organisation | University of Glasgow |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This is an academic partnership with Dr Douglas Morrison. He has developed methods using stable isotopes to monitor the metabolic effects on diet. He is also a partner in the SCFA programme |
Collaborator Contribution | He leads the stable isopote analysis |
Impact | There are a number of grants and papers that have come from the partnership |
Start Year | 2010 |
Description | Agents Hackathon |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | 20 people tool part in the agents workshop aimed at developing review papers and grants |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.imperial.ac.uk/metabolism-digestion-reproduction/research/digestive-diseases/nutrition-r... |
Description | Agents Hackathon number 2 |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | 35 scientists collaberates in a workshop aimed at developing review papers and new grands |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.imperial.ac.uk/metabolism-digestion-reproduction/research/digestive-diseases/nutrition-r... |
Description | Agents Workshops |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | We ran 2 workshops to develop the programme for Agents |
Year(s) Of Engagement Activity | 2022,2023 |
URL | https://www.imperial.ac.uk/metabolism-digestion-reproduction/research/digestive-diseases/nutrition-r... |
Description | Conferance on biulding international relations in nutrient sensing |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | over 100 people attended a series of workships aimed at biulding research collaberations |
Year(s) Of Engagement Activity | 2023 |
Description | Dr Bernadette Caroll tavel from Bristol Univesity to Imperial College London |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | To learn new skills with organoids |
Year(s) Of Engagement Activity | 2024 |
Description | Dr Tetsushi Kataura and Gailing Ma from University of Newcastle travel to Bristol Univesity for lab experiance |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | THe laboritory experiance to learn new skills |
Year(s) Of Engagement Activity | 2023,2024 |
Description | Great Exibition Road Festival |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | We demonstrated how food is digested as the role of the microbiota. This sparked a lot of questions |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.imperial.ac.uk/events/160698/great-exhibition-road-festival-2023/ |
Description | Imperial Murdoch Collaberation |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | This was a two week research scoping exercise |
Year(s) Of Engagement Activity | 2023 |
Description | Konstantinos Prokopidis Loughbough Univesity vist to Bristol Univesity |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | To increase lab skills |
Year(s) Of Engagement Activity | 2023,2024 |
Description | Nutrition Society Winter Meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | We had a stand at the conference to engage people in the network |
Year(s) Of Engagement Activity | 2023 |
Description | Nutrition and the Biology of Ageing |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Present the Agents network which got lots of interested and increase the numbers joining the network |
Year(s) Of Engagement Activity | 2022 |
Description | Oliver Shannon Newcastle visited Cardiff Univesity |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Developed skill through lab experiance. |
Year(s) Of Engagement Activity | 2018 |
Description | Visit to Colombia Univesity |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The aim was for the candidate to develop lab skills |
Year(s) Of Engagement Activity | 2023 |
Description | Visit to Univestiy of Glasgow by Konstantinos Prokopidis from Liverpool University |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | For tyhe candidate to pick up new lab skills |
Year(s) Of Engagement Activity | 2024 |