Evidence map›Paper›PMID 40726002›Full record

ArticleAging cell2025

Tissue-Specific Effects of Dietary Protein on Cellular Senescence Are Mediated by Branched-Chain Amino Acids.

Mariah F Calubag, Ismail Ademi, Isaac D Grunow, Lucia E Breuer, Reji Babygirija, Penelope Lialios, Sandra M Le, Michelle M Sonsalla, Julia A Illiano, Bailey A Knopf and 5 more

Abstract read
In one paragraph

Article in Aging cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. The emerging role of branched-chain amino acid metabolism in obesity.International journal of obesity (2005) · 2026
    Review
  5. Article
  6. Article
  7. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Mariah F CalubagDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.ORCID 0000-0003-4843-3668
Ismail AdemiDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Isaac D GrunowDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Lucia E BreuerDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Reji BabygirijaDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.ORCID 0000-0003-3719-5991
Penelope LialiosDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Sandra M LeDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Michelle M SonsallaDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.ORCID 0000-0001-8493-1416
Julia A IllianoWilliam S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, USA.
Bailey A KnopfDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.ORCID 0000-0001-7551-7248
Fan XiaoDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.ORCID 0009-0006-5265-5174
Dennis MintonDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Adam R KonopkaDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.ORCID 0000-0001-6655-6747
David A HarrisWilliam S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, USA.ORCID 0000-0001-5588-1632
Dudley W LammingDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.ORCID 0000-0002-0079-4467

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Pamela K Kreeger · 1985 to 2026
$142.6M
Translational analysis of a novel intervention to promote healthy aging.R01AG085898 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI RICKI J COLMAN, Dudley William Lamming · 2024 to 2026
$3.2M
The regulation of health and longevity by branched-chain amino acidsR01AG056771 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Dudley William Lamming · 2018 to 2026
$3.1M
The regulation of cancer and aging by methionineR01AG084156 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI VINCENT L. CRYNS, JOHN M DENU · 2023 to 2026
$2.5M
The regulation of health and longevity by branched-chain amino acidsRF1AG056771 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI LAMMING, DUDLEY WILLIAM · 2023 to 2023
$2.1M
Safer mTOR inhibition for human geroprotectionU01AG081482 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Adam R Konopka, Dudley William Lamming · 2023 to 2026
$1.8M
Dietary regulation of the hepatic epigenomeR01DK125859 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI DENU, JOHN M, LAMMING, DUDLEY WILLIAM · 2021 to 2023
$1.8M
The regulation of health and longevity by branched-chain amino acidsR56AG056771 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI LAMMING, DUDLEY WILLIAM · 2017 to 2017
$573k
Regulation of cellular senescence and metabolic health by dietary proteinF31AG082504 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI CALUBAG, MARIAH · 2023 to 2025
$146k
Dietary Interventions in Alzheimer’s DiseaseF31AG081115 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI BABYGIRIJA, REJI · 2023 to 2024
$102k
BLRD VA I01 BX004031BLRD VA IS1 BX005524NCI NIH HHS CA014520NCI NIH HHS P30 CA014520NIA NIH HHS AG056771NIA NIH HHS AG081115NIA NIH HHS AG081482NIA NIH HHS AG082504NIA NIH HHS AG084156NIA NIH HHS AG085898NIA NIH HHS AG09258601NIA NIH HHS F31 AG081115NIA NIH HHS F31 AG082504NIA NIH HHS R01 AG056771NIA NIH HHS R01 AG084156NIA NIH HHS R01 AG085898NIA NIH HHS R56 AG056771NIA NIH HHS RF1 AG056771NIA NIH HHS U01 AG081482NIDDK NIH HHS DK125859NIDDK NIH HHS R01 DK125859US Department of Veterans Affairs I01-BX004031US Department of Veterans Affairs IS1-BX005524
6 · The paper itself

Abstract

Dietary protein is a key regulator of healthy aging in both mice and humans. In mice, reducing dietary levels of the branched-chain amino acids (BCAAs) recapitulates many of the benefits of a low protein diet; BCAA-restricted diets extend lifespan, reduce frailty, and improve metabolic health, while BCAA supplementation shortens lifespan, promotes obesity, and impairs glycemic control. Recently, high protein diets have been shown to promote cellular senescence, a hallmark of aging implicated in many age-related diseases, in the liver of mice. Here, we test the hypothesis that the effects of high protein diets on metabolic health and on cellular senescence are mediated by BCAAs. We find that reducing dietary levels of BCAAs protects male mice from the negative metabolic consequences of both normal and high protein diets. Further, we identify tissue-specific effects of BCAAs on cellular senescence, with restriction of all three BCAAs-but not individual BCAAs-protecting from hepatic cellular senescence while potentiating cellular senescence in white adipose tissue. We also find that these effects are sex-specific. We find that the effects of BCAAs on hepatic cellular senescence are cell-autonomous, with lower levels of BCAAs protecting cultured cells from antimycin-A induced senescence. Our results demonstrate a direct effect of a specific dietary component on a hallmark of aging and suggest that cellular senescence may be highly susceptible to dietary interventions.

Indexed as

Amino Acids, Branched-ChainCellular SenescenceDietary ProteinsAnimalsFemaleHumansLiverMaleMiceMice, Inbred C57BLOrgan SpecificityAmino Acids, Branched-ChainDietary Proteins

Identifiers

PMID40726002
PMCPMC12507398

What Socratic holds

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Registered trials

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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 Socratic graph.