ArticleAging cell2016
Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer.
Article in Aging cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 258 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
258 citing papers in PubMed, 4 syntheses or guidelines pooled it, 369 citations in OpenAlex.
- Prenatal Maternal Stress and Infant Gut Microbiome in Human and Animal Studies: A Comprehensive Systematic Review.Developmental psychobiology · 2026Pooled it
- Rapamycin, Not Metformin, Mirrors Dietary Restriction-Driven Lifespan Extension in Vertebrates: A Meta-Analysis.Aging cell · 2025Pooled it
- Repurposing effect of cardiovascular-metabolic drug to increase lifespan: a systematic review of animal studies and current clinical trial progress.Frontiers in pharmacology · 2024Pooled it
- Pooled it
- The Hallmarks of Aging: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2026Review
- Article
- Plasma as Proxy for Tissue Metabolism When Extending Lifespan in Mice.Metabolites · 2026Article
- Geroprotective Effects of Drugs Modulating Metabolic Pathways: Perspectives of Pharmacology in Anti-Aging Therapy.International journal of molecular sciences · 2026Review
- Germ cells are hidden contributors to sex differences in vertebrate lifespan.The Journal of reproduction and development · 2026Review
- VCD-induced estropause fails to enhance responsiveness to 17α-estradiol in adult female mice.GeroScience · 2026Article
- 17α-Estradiol: A mildly feminizing estrogen with sex-specific metabolic and lifespan benefits.Ageing research reviews · 2026Review
- Article
- Sex differences in response to longevity interventions.Ageing research reviews · 2026Review
- Bench to bedside: is rapamycin headed for the docTOR?GeroScience · 2026Review
- Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice.GeroScience · 2026Article
- Cardiovascular ageing: hallmarks, signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- End-of-life pathology in UM-HET3 mice treated with 16 α‑hydroxyestradiol or late‑start canagliflozin.GeroScience · 2026Article
- Dietary restriction in aging and longevity.Nature aging · 2026Review
- Three-Month Administration of PB125 Modifies Histopathology, Redox Homeostasis, and Mobility in the Hartley Guinea Pig Model of Primary Osteoarthritis.Antioxidants (Basel, Switzerland) · 2026Article
- NRF2 pathway activation predicts poor prognosis in lung cancer: a cautionary note on antioxidant interventions.GeroScience · 2026Article
198 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
26 authors at 15 institutions in 4 countries.
Funding
Abstract
The National Institute on Aging Interventions Testing Program (ITP) evaluates agents hypothesized to increase healthy lifespan in genetically heterogeneous mice. Each compound is tested in parallel at three sites, and all results are published. We report the effects of lifelong treatment of mice with four agents not previously tested: Protandim, fish oil, ursodeoxycholic acid (UDCA) and metformin - the latter with and without rapamycin, and two drugs previously examined: 17-α-estradiol and nordihydroguaiaretic acid (NDGA), at doses greater and less than used previously. 17-α-estradiol at a threefold higher dose robustly extended both median and maximal lifespan, but still only in males. The male-specific extension of median lifespan by NDGA was replicated at the original dose, and using doses threefold lower and higher. The effects of NDGA were dose dependent and male specific but without an effect on maximal lifespan. Protandim, a mixture of botanical extracts that activate Nrf2, extended median lifespan in males only. Metformin alone, at a dose of 0.1% in the diet, did not significantly extend lifespan. Metformin (0.1%) combined with rapamycin (14 ppm) robustly extended lifespan, suggestive of an added benefit, based on historical comparison with earlier studies of rapamycin given alone. The α-glucosidase inhibitor, acarbose, at a concentration previously tested (1000 ppm), significantly increased median longevity in males and 90th percentile lifespan in both sexes, even when treatment was started at 16 months. Neither fish oil nor UDCA extended lifespan. These results underscore the reproducibility of ITP longevity studies and illustrate the importance of identifying optimal doses in lifespan studies.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.