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LifeSpan Network

Scientific excellence

Generating, corroborating and refuting scientific dogmas of ageing

Before LifeSpan, combining observational studies in humans with experimentation in animal models had only been marginally explored. What's more, it was never attemped in one collaborative effort. By doing just that, and by integrating research in development and ageing, LifeSpan managed to generate, corroborate and refute scientific dogmas of ageing.

Could we find the genetic pathways crucial for ageing? Would we be able to identify environmental influences affecting ageing and longevity? Could we possibly understand why ageing is so plastic, why lifespans vary so much and how this is regulated? Could we find out why ageing, health and disease are so much subject to change? LifeSpan set out to answer these and other questions. We strived to find connections between development and disease later in life. And we worked hard to establish mathematical and statistical models describing lifespans, life histories and biological processes affecting age.

Scientific output - Publications

  • In total more than 250 publications in scientific journals
  • Average Impact Factor (IF) of 6.7
  • Over 13% of the publications occurred in high impact journals (IF >10)

LifeSpan has generated new insights on the life course processes affecting ageing and health in old age.
  1. By taking the step from animal models to humans, LifeSpan showed that there is indeed evidence that genes regulating development in various species, primarily involved in insulin signaliing, are associated with late-life effects. Results apply to cohorts enriched for familial longevity as well as cohorts of very old people.
     
  2. LifeSpan has contributed to identifying pathways that are crucial for ageing (e.g. mTOR). Genome-wide association studies have been performed in several cohorts inside and outside Europe, generating multiple good candidate genes for longevity. Partners are now collaborating on meta-analyses and replication of positive findings.
     
  3. Several studies in LifeSpan have contributed to down playing the importance of specific signalling and metabolic pathways (e.g. sirtuins and free radicals) in the ageing process.
     
  4. The study of epigenetics in unique human cohorts and rat models has provided a convincing link between early-life events and late-life health. This effect can be mediated by modifications to the DNA earlier in life. LifeSpan has also shown that several loci in the human genome are affected by changes in the pre-natal environment (e.g. starvation) and associated with ill health in old age.
     
  5. A pioneering and successful initiative of LifeSpan was to create mathematical models to study physiological and genetic processes that are important for ageing and life trajectories. These models generate new hypotheses that can be tested in animal models and human cohorts.
     
  6. The immune system is very often involved in the diseases of old age. LifeSpan research has shown that infections in early-life (e.g. Cytomegalovirus, malaria) can have long standing effects on the immune function and late-life health in affluent and adverse environmental conditions.
     
  7. LifeSpan has contributed to a better understanding of ageing as part of individual life histories by performing state of the art genomic analyses and hormonal manipulations in organisms ranging from ants and butterflies to fish. These studies also provided new insights on the 'sex and death' relationship, where late-life trajectories are considered in the context of mating and fecundity.
     
  8. By using twin cohorts, LifeSpan research determined the impact of an early adverse environment on the late-life health trajectory. Studies in identical twin pairs have shown that differences in birth characteristics can predict old age disease patterns.