Molecular pathology of rare progeroid diseases

Trends Mol Med. 2021 Sep;27(9):907-922. doi: 10.1016/j.molmed.2021.06.011. Epub 2021 Jul 13.


Progeroid syndromes (PSs) are characterized by the premature onset of age-related pathologies. The genetic mutations underlying PSs are functionally linked to genome maintenance and repair, supporting the causative role of DNA damage accumulation in aging. Recent advances from studies in animal models of PSs have provided new insight into the role of DNA repair mechanisms in human disease and the physiological adaptations to accumulating DNA damage during aging. The molecular pathology of PSs is reminiscent of the natural aging process, highlighting the relevance for a wide range of age-related diseases. Recent progress has led to the development of novel therapeutic strategies against age-related diseases that are relevant to rare diseases as well as the general aging population.

Keywords: DNA damage response; DNA repair; age-related diseases; aging; progeroid syndromes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aged
  • Aging / genetics
  • Aging, Premature*
  • Animals
  • DNA Damage
  • DNA Repair / genetics
  • Humans
  • Pathology, Molecular*
  • Rare Diseases