ArticleAging cell2021
17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex.
Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 76 papers, 2 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
76 citing papers in PubMed, 2 syntheses or guidelines pooled 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
- Sex differences in pharmacological interventions and their effects on lifespan and healthspan outcomes: a systematic review.Frontiers in aging · 2023Pooled it
- Plasma as Proxy for Tissue Metabolism When Extending Lifespan in Mice.Metabolites · 2026Article
- Nicotinamide Mononucleotide Adenylyltransferase 1 and NADMetabolites · 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
- Hierarchical endpoints and win statistics for geromedicine trials.Nature aging · 2026Review
- Repurposing niclosamide to mitigate inflammaging: a review of multi-target mechanisms in cellular senescence and age-related decline.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Sex differences in response to longevity interventions.Ageing research reviews · 2026Review
- Article
- Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice.GeroScience · 2026Article
- Assessing health in aging male and female mice: does cardiac function dictate frailty or physical resilience?The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
- Dietary restriction in aging and longevity.Nature aging · 2026Review
- Inbred C57BL/6J and C57BL/6N mice exhibit differential vascular dysfunction compared with outbred UM-HET3 mice.American journal of physiology. Heart and circulatory physiology · 2026Article
- Mechanistic redundancy and hierarchy of aging mechanisms: implications for strategies to extend healthspan and biomarker integration.Frontiers in aging · 2026Review
- Changes in the brain [NADFrontiers in aging neuroscience · 2026Review
- Aging rate indicators and the search for anti-aging drugs.Frontiers in science · 2026Article
- Hormones, heat, and health: a comprehensive review of sex-based differences in brown and beige fat biology.Biology of sex differences · 2025Review
- Ndufs4GeroScience · 2025Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
22 authors.
Funding
Abstract
In genetically heterogeneous mice produced by the CByB6F1 x C3D2F1 cross, the "non-feminizing" estrogen, 17-α-estradiol (17aE2), extended median male lifespan by 19% (p < 0.0001, log-rank test) and 11% (p = 0.007) when fed at 14.4 ppm starting at 16 and 20 months, respectively. 90th percentile lifespans were extended 7% (p = 0.004, Wang-Allison test) and 5% (p = 0.17). Body weights were reduced about 20% after starting the 17aE2 diets. Four other interventions were tested in males and females: nicotinamide riboside, candesartan cilexetil, geranylgeranylacetone, and MIF098. Despite some data suggesting that nicotinamide riboside would be effective, neither it nor the other three increased lifespans significantly at the doses tested. The 17aE2 results confirm and extend our original reports, with very similar results when started at 16 months compared with mice started at 10 months of age in a prior study. The consistently large lifespan benefit in males, even when treatment is started late in life, may provide information on sex-specific aspects of aging.
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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.