The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Sirt1 Extends Life Span and Delays Aging in Mice through the Regulation of Nk2 Homeobox 1 in the DMH and LH
Open accessAbstract
SUMMARY The mammalian Sir2 ortholog Sirt1 plays an important role in metabolic regulation. However, the role of Sirt1 in the regulation of aging and longevity is still controversial. Here we demonstrate that brain-specific Sirt1-overexpressing (BRASTO) transgenic mice show significant life span extension in both males and females, and aged BRASTO mice exhibit phenotypes consistent with a delay in aging. These phenotypes are mediated by enhanced neural activity specifically in the dorsomedial and lateral hypothalamic nuclei (DMH and LH, respectively), through increased orexin type 2 receptor (Ox2r) expression. We identified Nk2 homeobox 1 (Nkx2-1) as a novel partner of Sirt1 that upregulates Ox2r transcription and colocalizes with Sirt1 in the DMH and LH. DMH/LH-specific knockdown of Sirt1, Nkx2-1, or Ox2r and DMH-specific Sirt1 overexpression further support the role of Sirt1/Nkx2-1/Ox2r-mediated signaling for longevity-associated phenotypes. Our findings indicate the importance of DMH/LH-predominant Sirt1 activity in the regulation of aging and longevity in mammals.
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Cites
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Cited by
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NAD+ and sirtuins in aging and disease
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Self-citationFrom discoveries in ageing research to therapeutics for healthy ageing
Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019) · Nature · doi:10.1038/s41586-019-1365-2 · Cited by 1,389
NAD + in aging, metabolism, and neurodegeneration
Verdin, E. (2015) · Science · doi:10.1126/science.aac4854 · Cited by 1,319
Metadata
- Authors
- Satoh, A., Brace, C. S., Rensing, N., Cliften, P., Wozniak, D. F., Herzog, E. D., Yamada, K. A., & Imai, S.-I.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 18
- Issue
- 3
- Pages
- 416-430
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2061077538
- Cited by
- 732
- References
- 14
- FWCI
- 22.19
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Sirt1 Extends Life Span and Delays Aging in Mice through the Regulation of Nk2 Homeobox 1 in the DMH and LH. https://app.cochat.ai/papers/10.1016/j.cmet.2013.07.013
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- Satoh, A., Brace, C. S., Rensing, N., Cliften, P., Wozniak, D. F., Herzog, E. D., Yamada, K. A., & Imai, S.-I. (2013). Sirt1 Extends Life Span and Delays Aging in Mice through the Regulation of Nk2 Homeobox 1 in the DMH and LH. Cell Metabolism. https://doi.org/10.1016/j.cmet.2013.07.013
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