Xeroderma Pigmentosum: A Model for Human Premature Aging

J Invest Dermatol. 2021 Apr;141(4S):976-984. doi: 10.1016/j.jid.2020.11.012. Epub 2021 Jan 9.


Aging results from intrinsic changes (chronologic) and damage from external exposures (extrinsic) on the human body. The skin is ideal to visually differentiate their unique features. Inherited diseases of DNA repair, such as xeroderma pigmentosum (XP), provide an excellent model for human aging due to the accelerated accumulation of DNA damage. Poikiloderma, atypical lentigines, and skin cancers, the primary cutaneous features of XP, occur in the general population but at a much older age. Patients with XP also exhibit ocular changes secondary to premature photoaging, including ocular surface tumors and pterygium. Internal manifestations of premature aging, including peripheral neuropathy, progressive sensorineural hearing loss, and neurodegeneration, are reported in 25% of patients with XP. Internal malignancies, such as lung cancer, CNS tumors, and leukemia and/or lymphoma, occur at a younger age in patients with XP, as do thyroid nodules. Premature ovarian failure is overrepresented among females with XP, occurring 20 years earlier than in the general population. Taken together, these clinical findings highlight the importance of DNA repair in maintaining genomic integrity. XP is a unique model of human premature aging, which is revealing new insights into aging mechanisms.

Publication types

  • Review

MeSH terms

  • Aging / genetics*
  • Aging, Premature / genetics*
  • Aging, Premature / pathology
  • DNA Damage
  • DNA Repair*
  • Humans
  • Mucous Membrane / pathology
  • Skin / pathology*
  • Xeroderma Pigmentosum / genetics*
  • Xeroderma Pigmentosum / pathology