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Approved research

Unravelling the determinants of successful ageing by examining longevity

Principal Investigator: Dr Karen Mather
Approved Research ID: 53850
Approval date: February 17th 2020

Lay summary

Exceptionally long-lived individuals often delay or escape common age-related diseases and can be seen as models of successful ageing. Exceptional longevity is moderately heritable suggesting genetic factors plays a role in determining survival. Therefore, these individuals can be used to study the influence of genetics on successful ageing. Examining the genetic overlap between exceptional longevity and different traits (e.g. Alzheimer's disease, protein levels) may reveal novel phenotypes and common pathways linked to successful ageing. This project aims to identify the different genetic factors and pathways associated with longevity/successful ageing. In the UKB, longevity data is not available for the majority of participants so parental longevity will be used as a proxy. Other longevity-related traits will also be investigated, including healthy longevity, which will be defined as parental longevity plus the absence of common diseases. The duration of the project will be three years. The results of this project will increase our knowledge of the factors associated with exceptional longevity and successful ageing and may facilitate innovative strategies to promote health in our ageing population.

Scope extension:

From our current project:

Our broad research question is to identify novel factors associated with human exceptional longevity, a model of successful ageing.

Our specific aims are:

  1. To identify the genetic determinants of exceptional longevity-related phenotypes
  2. Parental longevity
  3. Healthy longevity- absence of disease plus parental longevity
  4. Physical function longevity - healthy physical function plus parental longevity
  5. Cognitive function longevity - healthy cognitive performance plus parental longevity
  6. To identify interactions between genetics and the environment (e.g. smoking, physical activity, cognitive activity) for exceptional longevity-related phenotypes (described above)

New scope - In addition to above:

  1. To identify the genetic determinants of health-related phenotypes, including metabolic syndrome, and protein and metabolic biomarker levels.  This knowledge will then be used to examine the relationships between genetic risk for these phenotypes (e.g. by using polygenic risk scores) and longevity.
  2. Telomere length can be seen as a biomarker of ageing; the relationship between longevity-related phenotypes and telomere length will be assessed.