Midlife Growth Hormone Receptor Ablation Extends Healthy Lifespan and Induces Sex-Specific Hepatic Transcriptional Changes at Single-Cell Resolution

Duran-Ortiz S, List EO, Young JA, Ikeno Y, Zhu S, McHugh T, O'Connor PM, Kim M, Benayoun BA, Benencia F, Basu R, …, Kopchick JJ · 2026 · Aging cell · Atlas ID DUR2026

What this study shows

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.

Abstract

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Suppression of growth hormone (GH) signaling is known to be effective to extend lifespan in mammals, yet most models rely on congenital disruption of the GH/insulin-like growth factor-1 (IGF-1) axis. Whether modulation of this pathway later in life can still influence aging and the underlying cellular mechanisms remains incompletely understood. To address this, we ablated the growth hormone receptor (Ghr) at 12-months of age in mice (12mGHRKO), using a tamoxifen-inducible model.

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At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Tamoxifen-inducible whole-body Ghr knockout mice induced at 12 months of age (12mGHRKO), both sexes; liver single-nucleus RNA-seq); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Tamoxifen-inducible whole-body Ghr knockout mice induced at 12 months of age (12mGHRKO), both sexes; liver single-nucleus RNA-seq
Journal	Aging cell
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1111/acel.70695 · PMID 42698366 · Free full text (PMC13545643)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Tamoxifen-inducible whole-body Ghr knockout initiated at 12 months of age
Target	Growth hormone receptor (GHR) / GH-IGF-1 axis; hepatic GH-STAT5 signalling
Model	Mouse (12mGHRKO, both sexes)
Effect	Extended lifespan in both sexes from a midlife start; improved insulin sensitivity, neuromuscular and bone ageing in males; feminised male hepatic transcriptome

In the Atlas

Links in the pathway map

Supports Growth hormone / IGF-1 axis inhibits Longevity

Cite this paper

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Duran-Ortiz, S., List, E. O., Young, J. A., Ikeno, Y., Zhu, S., McHugh, T., O'Connor, P. M., Kim, M., Benayoun, B. A., Benencia, F., Basu, R., Gotte, E. A., Berryman, D. E., & Kopchick, J. J. (2026). Midlife Growth Hormone Receptor Ablation Extends Healthy Lifespan and Induces Sex-Specific Hepatic Transcriptional Changes at Single-Cell Resolution. Aging cell. https://doi.org/10.1111/acel.70695

@article{DUR2026,
  author       = {Duran-Ortiz, S. and List, E. O. and Young, J. A. and Ikeno, Y. and Zhu, S. and McHugh, T. and O'Connor, P. M. and Kim, M. and Benayoun, B. A. and Benencia, F. and Basu, R. and Gotte, E. A. and Berryman, D. E. and Kopchick, J. J.},
  title        = {{Midlife Growth Hormone Receptor Ablation Extends Healthy Lifespan and Induces Sex-Specific Hepatic Transcriptional Changes at Single-Cell Resolution}},
  journal      = {Aging cell},
  year         = {2026},
  doi          = {10.1111/acel.70695},
  note         = {PMID: 42698366},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record DUR2026) [Data set]. https://mtor-atlas.org/study/DUR2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_DUR2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record DUR2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/DUR2026/},
  doi          = {10.5281/zenodo.22059963}
}

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