Pathway link GHIGF1-LONGEVITY
Growth hormone / IGF-1 axis Longevity
Growth hormone / IGF-1 axis inhibits Longevity.
Less growth-hormone signalling, longer life in mice.
The conditions it holds under
Mouse only. A lifelong GH-receptor-antagonist transgenic (LIST2026; an earlier study of the same line did not detect extension) and a tamoxifen-inducible whole-body Ghr knockout started at 12 months (DUR2026). mTOR signalling was not measured in either, so the route through PI3K-Akt-mTOR is inferred, not shown here.
- Time it takes
- long exposure (days to weeks)
- Step
- indirect (through steps not drawn here)
- Measured in
- mouse
- Reaches people?
- plausible in people, not shown directly
- How settled
- settled in the literature
Studies behind it
| Year | Evidence | Study |
|---|---|---|
| 2026 | A | Growth Hormone Receptor Antagonism Extends LifespanLIST2026 Transgenic expression of a growth hormone receptor antagonist — the G119K mutant chemistry behind the FDA-approved drug Pegvisomant — significantly extended both median and maximal lifespan in male (p = 0.044; p = 0.0037) and female mice, with maximal lifespan extended by 186 and 265 days respectively. Two-year-old antagonist mice were less frail and had greater grip strength despite increased adiposity. This is the first demonstration that antagonising GH action (as opposed to congenital GH deficiency, as in Ames/Snell dwarfs) extends mammalian lifespan — the GH/IGF-1 axis sits upstream of PI3K-Akt-mTOR, which is why it belongs in this corpus. |
| 2026 | A | Midlife Growth Hormone Receptor Ablation Extends Healthy Lifespan and Induces Sex-Specific Hepatic Transcriptional Changes at Single-Cell ResolutionDUR2026 Deleting the growth hormone receptor in mice at 12 months of age, in middle age and long after development is complete, still significantly extended lifespan in both sexes without major effects on body growth. Males showed improved insulin sensitivity and were protected against age-related decline in neuromuscular performance and bone microarchitecture despite increased adiposity. Liver snRNA-seq revealed sex-dimorphic remodelling, including a shift toward feminised gene expression in male hepatocytes consistent with loss of pulsatile GH-STAT5 signalling. Important because most GH/IGF-1 longevity models are congenital: this shows a midlife start is still sufficient, which matters for translating growth-signalling (and by extension mTOR-adjacent) interventions to adults. |
Points the other way
No study in the Atlas contradicts this link. That means none in this curated set, not none in the literature.
Who has checked this
- Checked by
- No researcher outside the project has checked this link yet.
- Curator sign-off
- Not signed off yet. This link was drafted with AI help and has not been reviewed link by link; treat it as a proposal until it is.
- Curated by
- Oliver Barton, with AI help for drafting; see how links are checked.
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