Award

Biological determinants of ageing and late life health, and their pharmacological manipulation.

Description: Age is the main risk factor for common, debilitating conditions including cancer, cardiovascular disease and neurodegeneration. Single gene mutations can extend healthy lifespan in laboratory animals. The mechanisms involved are evolutionarily conserved, with genetic and pharmacological inhibition of the nutrient-sensing insulin/insulin-like growth factor/TOR (IIT) signalling network extending healthy lifespan in yeast, nematode worms, fruit flies and mammals. Dietary restriction (DR) also exten ds healthy lifespan in these organisms, at least in part through altered IIT activity. Both reduced IIT activity and DR induce a broad-spectrum improvement in health and protection against pathology during ageing. Thus, amelioration of the ageing process can protect against diseases of ageing. This programme will have three key goals: 1. To discover how reduced activity IIT activity improves health during ageing, through experimental analysis of signalling and effector mechanisms in model orga nisms; 2 To recapitulate and extend improved health during ageing by pharmacological manipulation of key target molecules, both with existing drugs and new probe molecules; 3. To use results generated in 1 and 2, together with population genetic and drug response information from humans, to translate the discoveries into improvement in health of older people.
Amount: £4,847,000
Funding type: research
Funder scheme: Strategic Award - Science
Start date: 2013-04-03
End date: 2022-01-02
Investigator: Prof Linda Partridge
Institution: University College London
Funded outputs count: 122
Funder award ID: 098565/Z/12/Z
OpenAlex ID: G7115730731
2024 · Suchira Gallage, Elaine E. Irvine, et al. · Nature Aging · 31
2024 · Anissa A. Widjaja, Wei-Wen Lim, et al. · Nature · 238
2024 · Imanol Duran, Joaquim Pombo, et al. · Nature Communications · 85
2024 · Enric Ureña, Bowen Xu, et al. · Proceedings of the National Academy of Sciences · 17
2022 · Seok-Ting J. Ang, Elisa M. Crombie, et al. · Nature Communications · 29
2022 · Elisa M. Crombie, Seonyoung Kim, et al. · Journal of Cachexia Sarcopenia and Muscle · 32
2022 · David Gems · Ageing Research Reviews · 127
2021 · Brian L. H. Wong, Ines Siepmann, et al. · Frontiers in Public Health · 15
2021 · Suchira Gallage, Adnan Ali, et al. · Cellular and Molecular Gastroenterology and Hepatology · 20
2021 · Mihaly Varadi, Stephen Anyango, et al. · Nucleic Acids Research · 82
2021 · Carina C. Kern, StJohn Townsend, et al. · Nature Communications · 55
2021 · David Gems, Carina C. Kern, et al. · Frontiers in Cell and Developmental Biology · 43
2021 · Yahyah Aman, Tomas Schmauck-Medina, et al. · Nature Aging · 1,314
2021 · David Gems, João Pedro de Magalhães · Ageing Research Reviews · 134
2021 · Daniel K. Fabian, Matías Fuentealba, et al. · Immunity & Ageing · 73
2021 · Handan Melike Dönertaş, Daniel K. Fabian, et al. · Nature Aging · 349
2021 · Evgeniy R. Galimov, David Gems · Philosophical Transactions of the Royal Society B Biological Sciences · 27
2021 · Ekin Bolukbasi, Nathaniel S. Woodling, et al. · Proceedings of the National Academy of Sciences · 14
2021 · Daniel K Fabian, Handan Melike Dönertaş, et al. · Genome Biology and Evolution · 10
2021 · Valerie Kuan, Helen C. Fraser, et al. · Scientific Reports · 53
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