Evidence map›Paper›PMID 40232348›Full record

ArticleGeroScience2025

German longevity study reveals novel rare pro-longevity alleles clustering in mTOR signaling pathway.

Daniel Kolbe, Janina Dose, Pasquale Putter, Malte Ziemann, Matthias Laudes, Regeneron Genetics Center, P Eline Slagboom, Andre Franke, Joris Deelen, Almut Nebel

Abstract read
In one paragraph

Article in GeroScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Daniel KolbeInstitute of Clinical Molecular Biology, Kiel University, Kiel, Germany. d.kolbe@ikmb.uni-kiel.de.ORCID 0000-0002-6607-7591
Janina DoseInstitute of Clinical Molecular Biology, Kiel University, Kiel, Germany.
Pasquale PutterMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
Malte ZiemannInstitute of Transfusion Medicine, University Hospital Schleswig-Holstein, Lübeck, Germany.
Matthias LaudesInstitute for Diabetes and Clinical Metabolic Research, University Hospital Schleswig-Holstein, Kiel, Germany.
Regeneron Genetics Center
P Eline SlagboomMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
Andre FrankeInstitute of Clinical Molecular Biology, Kiel University, Kiel, Germany.
Joris DeelenMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
Almut NebelInstitute of Clinical Molecular Biology, Kiel University, Kiel, Germany.

Funding

Deutsche Forschungsgemeinschaft 390884018Deutsche Forschungsgemeinschaft 400993799European Commission 101041331Nederlandse Organisatie voor Wetenschappelijk Onderzoek 09120012010052Seventh Framework Programme 259679VOILA Consortium 457001001
6 · The paper itself

Abstract

In this study, we investigated the contribution of rare coding variants to human longevity by analyzing whole exome sequencing data from 1245 German long-lived individuals (LLI) and 4105 geographically matched younger controls. We identified novel exome-wide significant associations at both the single-variant and gene level, with a significant over-representation of genes involved in mechanistic target of rapamycin (mTOR) signaling. As such, three rare single variants in the mTOR-pathway genes RPS6, FLCN, and SIK3 were enriched in LLI. Additionally, RWDD1 emerged as a strong candidate gene for longevity, with LLI exhibiting a statistically significant burden of rare missense variants in this gene. Other associations involved PRAC2, SLC16 A6, FOCAD, IHH, MESD, HOXA4, and DNAJB13. Furthermore, we observed an enrichment of protein-truncating variants in the genes ASXL1 and TET2 amongst LLI, likely as a result of clonal haematopoiesis. The study emphasizes the role of rare variants in human longevity, particularly through mTOR signaling.

Indexed as

LongevitySignal TransductionTOR Serine-Threonine KinasesAgedAged, 80 and overAllelesExome SequencingFemaleGermanyHumansMaleMiddle AgedMTOR protein, humanTOR Serine-Threonine KinasesExome-wide association analysisGeneticsHuman longevityMTOR signalingRare variants

Identifiers

PMID40232348
PMCPMC12181166

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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.