Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production
Open accessAbstract
Single-gene mutations that extend lifespan provide valuable tools for the exploration of the molecular basis for age-related changes in cell and tissue function and for the pathophysiology of age-dependent diseases. We show here that mice homozygous for loss-of-function mutations at the Pit1 (Snell dwarf) locus show a >40% increase in mean and maximal longevity on the relatively long-lived (C3H/HeJ × DW/J)F 1 background. Mutant dw J /dw animals show delays in age-dependent collagen cross-linking and in six age-sensitive indices of immune system status. These findings thus demonstrate that a single gene can control maximum lifespan and the timing of both cellular and extracellular senescence in a mammal. Pituitary transplantation into dwarf mice does not reverse the lifespan effect, suggesting that the effect is not due to lowered prolactin levels. In contrast, homozygosity for the Ghrhr lit mutation, which like the Pit1 dw mutation lowers plasma growth hormone levels, does lead to a significant increase in longevity. Male Snell dwarf mice, unlike calorically restricted mice, become obese and exhibit proportionately high leptin levels in old age, showing that their exceptional longevity is not simply due to alterations in adiposity per se . Further studies of the Pit1 dw mutant, and the closely related, long-lived Prop-1 df (Ames dwarf) mutant, should provide new insights into the hormonal regulation of senescence, longevity, and late life disease.
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In mice, reducing growth hormone signalling from the hypothalamic-pituitary axis extends lifespan.
“In mice, reducing the growth hormone signalling from the hypothalamic–pituitary axis extends lifespan (93).”
From Neural mechanisms of ageing and cognitive decline (2010) · cites this paper as [93]
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- Authors
- Flurkey, K., Papaconstantinou, J., Miller, R. A., & Harrison, D. E.
- Affiliations
- University of Michigan (US)
- ORCID
- Miller, Richard A.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-05-22
- Volume
- 98
- Issue
- 12
- Pages
- 6736-6741
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC34422
- OpenAlex
- W2159979637
- Cited by
- 826
- References
- 34
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 17 · 2023: 24 · 2022: 21 · 2021: 23 · 2020: 25 · 2019: 24 · 2018: 23 · 2017: 28 · 2016: 22 · 2015: 37 · 2014: 28 · 2013: 32 · 2012: 30
- FWCI
- 16.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- National Institutes of Health (5r01ag011643-05, 1f32ag005429-01)
- National Institute on Aging (P60AG008808, AG05429, AG-11643, AG 16622, AG-08808, R01AG016622, P30AG024832)
- National Cancer Institute (CA34190)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- lifespan extension, growth hormone deficiency, immunosenescence, collagen cross-linking, cellular senescence, pituitary transplantation, prolactin, leptin, obesity, longevity, single-gene mutations
- MeSH terms
- Aging, Animals, Body Weight, Collagen, DNA-Binding Proteins, Female, Insulin-Like Growth Factor I, Longevity, Male, Mice, Inbred C3H, Mice, Mutant Strains, Pituitary Gland, Growth Hormone, T-Lymphocytes, Transcription Factors, T-Lymphocyte Subsets, Leptin, Transcription Factor Pit-1, Mice
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 ›
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