The DOI matches its Crossref record; 49 of the 50 references it cites were found in a registry or an index.
The HIF-1 Hypoxia-Inducible Factor Modulates Lifespan in C. elegans
Open accessAbstract
During normal development or during disease, animal cells experience hypoxic (low oxygen) conditions, and the hypoxia-inducible factor (HIF) transcription factors implement most of the critical changes in gene expression that enable animals to adapt to this stress. Here, we examine the roles of HIF-1 in post-mitotic aging. We examined the effects of HIF-1 over-expression and of hif-1 loss-of-function mutations on longevity in C. elegans, a powerful genetic system in which adult somatic cells are post-mitotic. We constructed transgenic lines that expressed varying levels of HIF-1 protein and discovered a positive correlation between HIF-1 expression levels and lifespan. The data further showed that HIF-1 acted in parallel to the SKN-1/NRF and DAF-16/FOXO transcription factors to promote longevity. HIF-1 over-expression also conferred increased resistance to heat and oxidative stress. We isolated and characterized additional hif-1 mutations, and we found that each of 3 loss-of-function mutations conferred increased longevity in normal lab culture conditions, but, unlike HIF-1 over-expression, a hif-1 deletion mutation did not extend the lifespan of daf-16 or skn-1 mutants. We conclude that HIF-1 over-expression and hif-1 loss-of-function mutations promote longevity by different pathways. These data establish HIF-1 as one of the key stress-responsive transcription factors that modulate longevity in C. elegans and advance our understanding of the regulatory networks that link oxygen homeostasis and aging.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Numerous reports have indicated that the HIF pathway has a role in life span of C. elegans (Chen et al., 2009; Zhang et al., 2009).”
From SirT3 suppresses hypoxia inducible factor 1α and tumor growth by inhibiting mitochondrial ROS production (2011) · cites this paper as Zhang et al., 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A C. elegans mutant that lives twice as long as wild type
Kenyon, C., Chang, J., Gensch, E., Rudner, A., & Tabtiang, R. (1993) · Nature · doi:10.1038/366461a0 · Cited by 3,387
Epstein, A. C. R., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00507-4 · Cited by 3,333
Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.
Kaelin, W. G., & Ratcliffe, P. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.04.009 · Cited by 3,251 · cited 1×
“HIF stability and activity are influenced by reactive oxygen species, citric acid cycle intermediates, Fe(II) availability, and intracellular signaling events [1,3].”
BackgroundKimura, K. D., Tissenbaum, H. A., Liu, Y., & Ruvkun, G. (1997) · Science · doi:10.1126/science.277.5328.942 · Cited by 2,250
Ogg, S., Paradis, S., Gottlieb, S., Patterson, G. I., Lee, L., Tissenbaum, H. A., & Ruvkun, G. (1997) · Nature · doi:10.1038/40194 · Cited by 1,935
Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
Tissenbaum, H. A., & Guarente, L. (2001) · Nature · doi:10.1038/35065638 · Cited by 1,603
Regulation of aging and age-related disease by DAF-16 and heat-shock factor
Hsu, A.-L., Murphy, C. T., & Kenyon, C. (2003) · Science · doi:10.1126/science.1083701 · Cited by 1,513
Hypoxia-inducible factor 1: master regulator of O2 homeostasis
Semenza, G. L. (1998) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(98)80016-6 · Cited by 1,092
Lin, K., Hsin, H., Libina, N., & Kenyon, C. J. (2001) · Nature Genetics · doi:10.1038/88850 · Cited by 1,027
Henderson, S. T., & Johnson, T. E. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00594-2 · Cited by 949
Flagged first, then by citations
1 of the 50 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 201–211 of 211
The role of Banf1 in mechanisms of cellular ageing and cancer prognosis
Plowman, J. (2024) · Queensland University of Technology · doi:10.5204/thesis.eprints.247163
Götz, M. S., Hayman, D. J., Adams, G., Obata, F., & Simons, M. J. P. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2518812123 · Cited by 1
The hypoxic response extends lifespan through a bioaminergic and peptidergic neural circuitPreprint
Kitto, E. S., Huang, S., Bhandari, M., Tian, C., Cox, R. L., Beydoun, S., Wang, E. Q., Shave, D., Miller, H. A., Easow, S. A., et al. (2025) · eLife · doi:10.7554/elife.107651.1
Rewarding touch limits lifespan through neural to intestinal signaling
Kitto, E. S., Beydoun, S., & Leiser, S. F. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2423780122
Li, J., Wang, M., Lo, C., Yen, L., Yu, C., Lyu, Y.-J., & Chen, P. (2026) · Nucleic Acids Research · doi:10.1093/nar/gkag070
Raamsdonk, J. M. V. (2026) · Frontiers in Aging · doi:10.3389/fragi.2026.1808540 · Cited by 1
Mechanisms and function of mitophagy in adaptation to heat stress during development of C. elegans
Chen, Y. (2019) · theses.fr (ABES) · doi:10.70675/c8145e7bz8153z43acz8532z3ea5954dd01c
Li, M., Guo, Z., Jiang, Y., Zhao, L., Zhang, Y., Meng, L., Ni, C., Chen, Z., & Zhang, L. (2026) · Advanced Biology · doi:10.1002/adbi.70146
Self-citationThe hypoxic response extends lifespan through a bioaminergic and peptidergic neural circuitPreprint
Kitto, E. S., Huang, S., Bhandari, M., Tian, C., Cox, R. L., Beydoun, S., Wang, E., Shave, D., Miller, H. A., Easow, S. A., et al. (2026) · eLife · doi:10.7554/elife.107651.2
Metadata
- Authors
- Zhang, Y., Shao, Z., Zhai, Z., Shen, C., & Powell-Coffman, J. A.
- Affiliations
- Iowa State University (US)
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-07-27
- Volume
- 4
- Issue
- 7
- Pages
- e6348
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2711329
- OpenAlex
- W2076724288
- Cited by
- 211
- References
- 50
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 11 · 2023: 5 · 2022: 10 · 2021: 8 · 2020: 10 · 2019: 14 · 2018: 12 · 2017: 7 · 2016: 16 · 2015: 22 · 2014: 18 · 2013: 9 · 2012: 11
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Iowa State University Digital Repository (Iowa State University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Iowa State University
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM078424)
- National Center for Research Resources
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- HIF-1, hypoxia-inducible factor, lifespan, longevity, Caenorhabditis elegans, DAF-16/FOXO, transcription factors, oxidative stress resistance, heat stress resistance, oxygen homeostasis, stress response, loss-of-function mutations
- MeSH terms
- Animals, Longevity, Mutation, Transcription Factors, Caenorhabditis elegans, Reverse Transcriptase Polymerase Chain Reaction, Caenorhabditis elegans Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
