Genetics of extreme human longevity to guide drug discovery for healthy ageing

Zhengdong D. Zhang, Sofiya Milman, Jhih Rong Lin, Shayne Wierbowski, Haiyuan Yu, Nir Barzilai, Vera Gorbunova, Warren C. Ladiges, Laura J. Niedernhofer, Yousin Suh, Paul D. Robbins, Jan Vijg

Research output: Contribution to journalReview articlepeer-review

30 Scopus citations


Ageing is the greatest risk factor for most common chronic human diseases, and it therefore is a logical target for developing interventions to prevent, mitigate or reverse multiple age-related morbidities. Over the past two decades, genetic and pharmacologic interventions targeting conserved pathways of growth and metabolism have consistently led to substantial extension of the lifespan and healthspan in model organisms as diverse as nematodes, flies and mice. Recent genetic analysis of long-lived individuals is revealing common and rare variants enriched in these same conserved pathways that significantly correlate with longevity. In this Perspective, we summarize recent insights into the genetics of extreme human longevity and propose the use of this rare phenotype to identify genetic variants as molecular targets for gaining insight into the physiology of healthy ageing and the development of new therapies to extend the human healthspan.

Original languageEnglish (US)
Pages (from-to)663-672
Number of pages10
JournalNature Metabolism
Issue number8
StatePublished - Aug 1 2020

ASJC Scopus subject areas

  • Physiology (medical)
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cell Biology


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