Evidence mapPaperPMID 35948858Full record

ArticleGeroScience2023

High-throughput sequencing analysis of nuclear-encoded mitochondrial genes reveals a genetic signature of human longevity.

Brenda Gonzalez, Archana Tare, Seungjin Ryu, Simon C Johnson, Gil Atzmon, Nir Barzilai, Matt Kaeberlein, Yousin Suh

Open access · hybridAbstract read
In one paragraph

Article in GeroScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 29% of its field
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

5 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. 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

8 authors at 2 institutions in 3 countries.

Brenda Gonzalez *Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Archana Tare *Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Seungjin Ryu *Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Simon C JohnsonDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Gil AtzmonDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Nir BarzilaiDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Matt KaeberleinDepartment of Pathology, University of Washington, Seattle, WA, 98195, USA.
Yousin SuhDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. ys3214@cumc.columbia.edu.ORCID 0000-0002-6014-3084
Albert Einstein College of Medicine · USUniversity of Washington · US

Funding

PROGRAM ENRICHMENTP30AG013280 · UNIVERSITY OF WASHINGTON · 1995 to 2025
$6.6M
THE IMPACT OF CELLULAR DEFENSE ON THE ROLE OF Ku80 IN GENOME MAINTENANCE AND LONGP01AG017242 · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · 1999 to 2005
$5.8M
A stress-induced promoter pause release program in cardiomyocytes protecting against myocardial infarctionR01HL150521 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MICHAEL G ROSENFELD · 2022 to 2023
$1.3M
Training in Aging ResearchT32AG023475 · ALBERT EINSTEIN COL OF MED YESHIVA UNIV · 2004 to 2025
$952k
Human tissue specific age-related gene expression changes, their genetic regulations and the link to human diseasesR01AG055501 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Zhidong Tu · 2022 to 2022
$371k
NHLBI NIH HHS R01 HL150521NIA NIH HHS P01 AG017242NIA NIH HHS P30 AG013280NIA NIH HHS P30 AG038072NIA NIH HHS R01 AG055501NIA NIH HHS R01 AG057433NIA NIH HHS R01 AG057706NIA NIH HHS R01 AG057909NIA NIH HHS R01 AG061521NIA NIH HHS R01 AG069750NIA NIH HHS RF1 AG057341NIA NIH HHS T32 AG023475NIDDK NIH HHS R01 DK127778
6 · The paper itself

Abstract

Mitochondrial dysfunction is a well-known contributor to aging and age-related diseases. The precise mechanisms through which mitochondria impact human lifespan, however, remain unclear. We hypothesize that humans with exceptional longevity harbor rare variants in nuclear-encoded mitochondrial genes (mitonuclear genes) that confer resistance against age-related mitochondrial dysfunction. Here we report an integrated functional genomics study to identify rare functional variants in ~ 660 mitonuclear candidate genes discovered by target capture sequencing analysis of 496 centenarians and 572 controls of Ashkenazi Jewish descent. We identify and prioritize longevity-associated variants, genes, and mitochondrial pathways that are enriched with rare variants. We provide functional gene variants such as those in MTOR (Y2396Lfs*29), CPS1 (T1406N), and MFN2 (G548*) as well as LRPPRC (S1378G) that is predicted to affect mitochondrial translation. Taken together, our results suggest a functional role for specific mitonuclear genes and pathways in human longevity.

Indexed as

Genes, MitochondrialLongevityAged, 80 and overAgingHigh-Throughput Nucleotide SequencingHumansMitochondriaAgingCentenarianGenetic variantLongevityMitochondria

Identifiers

PMID35948858
PMCPMC9886794
OpenAlexW4290988380

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.