Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males.

Harrison DE, Strong R, Allison DB, Ames BN, Astle CM, Atamna H, Fernandez E, Flurkey K, Javors MA, Nadon NL, Nelson JF, …, Miller RA · 2014 · Aging Cell · Atlas ID HAR2014

What this study shows

Beyond rapamycin, the same ITP program found acarbose extended male median lifespan by 22% - evidence that the registry surfaces real positive hits too, not only negative results.

Abstract

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Four agents--acarbose (ACA), 17-α-estradiol (EST), nordihydroguaiaretic acid (NDGA), and methylene blue (MB)--were evaluated for lifespan effects in genetically heterogeneous mice tested at three sites. Acarbose increased male median lifespan by 22% (P < 0.0001), but increased female median lifespan by only 5% (P = 0.01). This sexual dimorphism in ACA lifespan effect could not be explained by differences in effects on weight. Maximum lifespan (90th percentile) increased 11% (P < 0.001) in males and 9% (P = 0.001) in females.

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mouse (genetically heterogeneous, ITP, 3 sites)); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Mouse (genetically heterogeneous, ITP, 3 sites)
Journal	Aging Cell
Year	2014
Peer reviewed	Yes
Record last updated	2026-07-29
Source	DOI 10.1111/acel.12170 · PMID 24245565 · Free full text (PMC3954939)

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	Acarbose, 17-α-estradiol, NDGA, methylene blue (dietary/pharmacologic)
Target	Metabolic/aging pathways
Model	Mouse (genetically heterogeneous, NIA ITP, 3 sites)
Effect	Acarbose extended male median lifespan by 22% (female 5%); EST and NDGA extended lifespan preferentially in males
Dose	Acarbose at 1000 mg kg −1 diet (1000 ppm) from 4 months of age
Sample size	not stated
Effect size	Male median lifespan increased by 22% (P < 0.0001); female median lifespan increased by 5% (P = 0.01) (pooled data).
Limitations	not stated

In the Atlas

Open questions that cite this study

Cited as supporting evidence for the open question Does the larger rapamycin benefit in female mice survive equal drug exposure, and is it set by hormones or by chromosomes?.
Cited as supporting evidence for the open question Rapamycin + AMPK-axis drugs (acarbose / metformin): a male-mouse survival signal from cross-cohort comparison, untested in humans.

Cite this paper

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Harrison, D. E., Strong, R., Allison, D. B., Ames, B. N., Astle, C. M., Atamna, H., Fernandez, E., Flurkey, K., Javors, M. A., Nadon, N. L., Nelson, J. F., Pletcher, S., Simpkins, J. W., Smith, D., Wilkinson, J. E., & Miller, R. A. (2014). Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males. Aging Cell. https://doi.org/10.1111/acel.12170

@article{HAR2014,
  author       = {Harrison, D. E. and Strong, R. and Allison, D. B. and Ames, B. N. and Astle, C. M. and Atamna, H. and Fernandez, E. and Flurkey, K. and Javors, M. A. and Nadon, N. L. and Nelson, J. F. and Pletcher, S. and Simpkins, J. W. and Smith, D. and Wilkinson, J. E. and Miller, R. A.},
  title        = {{Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males}},
  journal      = {Aging Cell},
  year         = {2014},
  doi          = {10.1111/acel.12170},
  note         = {PMID: 24245565},
}

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 HAR2014) [Data set]. https://mtor-atlas.org/study/HAR2014/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_HAR2014,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record HAR2014},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/HAR2014/},
  doi          = {10.5281/zenodo.22059963}
}

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