ArticleeLife2020
Germline burden of rare damaging variants negatively affects human healthspan and lifespan.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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
14 citing papers in PubMed, 19 citations in OpenAlex.
- Effect of aspirin on healthspan in community-dwelling older adults: the ASPirin in reducing events in the elderly study.Age and ageing · 2026Trial
- Impact of Vaccines Across the Lifespan: A New Perspective in Public Health-Conclusions of an Expert Panel-Part 1.Vaccines · 2026Review
- Genomic Perspective on Heterogeneity of Organs and Body Aging.Aging cell · 2026Review
- Depletion of loss-of-function germline mutations in centenarians reveals longevity genes.Nature communications · 2024Article
- Comparative genomics of Balto, a famous historic dog, captures lost diversity of 1920s sled dogs.Science (New York, N.Y.) · 2023Article
- The burden of rare protein-truncating genetic variants on human lifespan.Nature aging · 2022Article
- Current Trends and Approaches to the Search for Genetic Determinants of Aging and Longevity.Russian journal of genetics · 2022Article
- Molecular Damage in Aging.Nature aging · 2021Review
- Rare genetic coding variants associated with human longevity and protection against age-related diseases.Nature aging · 2021Article
- Review
- The Ground Zero of Organismal Life and Aging.Trends in molecular medicine · 2021Review
- Review
- Genetics of extreme human longevity to guide drug discovery for healthy ageing.Nature metabolism · 2020Review
- Article
Corrections and comments
- Commented on by
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Heritability of human lifespan is 23-33% as evident from twin studies. Genome-wide association studies explored this question by linking particular alleles to lifespan traits. However, genetic variants identified so far can explain only a small fraction of lifespan heritability in humans. Here, we report that the burden of rarest protein-truncating variants (PTVs) in two large cohorts is negatively associated with human healthspan and lifespan, accounting for 0.4 and 1.3 years of their variability, respectively. In addition, longer-living individuals possess both fewer rarest PTVs and less damaging PTVs. We further estimated that somatic accumulation of PTVs accounts for only a small fraction of mortality and morbidity acceleration and hence is unlikely to be causal in aging. We conclude that rare damaging mutations, both inherited and accumulated throughout life, contribute to the aging process, and that burden of ultra-rare variants in combination with common alleles better explain apparent heritability of human lifespan.
Indexed as
Identifiers
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.