The Ercc1-/Δ mouse model of accelerated senescence and aging for identification and testing of novel senotherapeutic interventions

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4 Scopus citations

Abstract

Progeroid murine models represent an emerging tool to investigate mechanisms of aging in an expedient and efficient manner. One prominent mechanism of aging is the accumulation of DNA damage and subsequent increase in cellular senescence, leading to age related pathologies. Ercc1-/Δ hypomorphic mice, which have a reduced level of the ERCC1-XPF DNA repair endonuclease complex, accumulate spontaneously occurring endogenous DNA damage similar to naturally aged mice, but at a faster rate. The resulting genomic damage gives rise to a senescent cell burden that is comparable to that of a naturally aged mouse. In fact, the expression of senescence and senescence-associated secretory phenotype (SASP) markers in 4-5-month-old Ercc1-/Δ mice, along with other measurements of senescence, were equivalent and never exceeded the extent of that found in naturally aged mice. Furthermore, many features of both natural murine aging and human aging are present in Ercc1-/Δ mice. An emerging use of these mice is the ability to study age-related signaling pathways, including identifying different types of senescent cells and their key senescent cell anti-apoptotic pathways (SCAPs). Most importantly, this model represents a rapid, cost-effective mouse model for the evaluation in vivo of senolytic drugs and other gerotherapeutics.

Original languageEnglish (US)
Pages (from-to)24481-24483
Number of pages3
JournalAging
Volume12
Issue number24
DOIs
StatePublished - 2020

Bibliographical note

Funding Information:
This work was supported by NIH grants P01AG043376, P01AG062412, P01AG062413, U19AG056278, R56AG4059675, and R01AG063543 to PDR.

Publisher Copyright:
© 2020. Wong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. All Rights Reserved.

Keywords

  • DNA damage
  • DNA repair
  • aging
  • cellular senescence
  • senolytic

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