4.4 Article

In vivo cyclic induction of the FOXM1 transcription factor delays natural and progeroid aging phenotypes and extends healthspan

期刊

NATURE AGING
卷 2, 期 5, 页码 397-+

出版社

SPRINGERNATURE
DOI: 10.1038/s43587-022-00209-9

关键词

-

资金

  1. GenomePT project [POCI-01-0145-FEDER-022184]
  2. Portuguese Platform of Bioimaging [PPBI-POCI-01-0145-FEDER-022122]
  3. FundacAo para a Ciencia e a Tecnologia (FCT) [PTDC/MED-OUT/2747/2020]
  4. Progeria Research Foundation [PRF 2020-78]
  5. FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the COMPETE 2020-Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020
  6. Portuguese funds through FCT, I. P. [POCI-01-0145-FEDER-031120 (PTDC/BIA-CEL/31120/2017)]
  7. COMPETE 2020/PORTUGAL 2020 through FEDER [POCI-01-0145-FEDER-007274 i3S]
  8. National Institutes of Health
  9. FCT fellowship [PD/BD/128000/2016]
  10. [IF/00916/2014]
  11. [CEECIND/00654/2020]

向作者/读者索取更多资源

The FOXM1 gene plays a crucial role in maintaining cellular homeostasis and has the potential to delay cellular and organismal aging, thereby mitigating aging-related pathologies.
The FOXM1 transcription factor exhibits pleiotropic C-terminal transcriptional and N-terminal non-transcriptional functions in various biological processes critical for cellular homeostasis. We previously found that FOXM1 repression during cellular aging underlies the senescence phenotypes, which were vastly restored by overexpressing transcriptionally active FOXM1. Yet, it remains unknown whether increased expression of FOXM1 can delay organismal aging. Here, we show that in vivo cyclic induction of an N-terminal truncated FOXM1 transgene on progeroid and naturally aged mice offsets aging-associated repression of full-length endogenous Foxm1, reinstating both transcriptional and non-transcriptional functions. This translated into mitigation of several cellular aging hallmarks, as well as molecular and histopathological progeroid features of the short-lived Hutchison-Gilford progeria mouse model, significantly extending its lifespan. FOXM1 transgene induction also reinstated endogenous Foxm1 levels in naturally aged mice, delaying aging phenotypes while extending their lifespan. Thus, we disclose that FOXM1 genetic rewiring can delay senescence-associated progeroid and natural aging pathologies.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据