Evidence map›Paper›PMID 42542973›Full record

ArticleAging cell2026

Activation of the Lactate Receptor GPR81 Ameliorates Senescence Hallmarks and Improves Muscle Function in Cellular and Progeroid Models of Aging.

Pihu Mehrotra, Sai Harsha Bhamidipati, Pedro Lei, John Toftegaard, Debanik Choudhury, Maryam Elsayed, Yali Zhang, Jianmin Wang, Shweta Chitkara, G Ekin Atilla-Gokcumen and 2 more

Abstract read
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In one paragraph

Article in Aging cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Pihu MehrotraDepartment of Chemical and Biological Engineering, University at Buffalo, Buffalo, New York, USA.ORCID https://orcid.org/0000-0001-9369-5013
Sai Harsha BhamidipatiDepartment of Chemical and Biological Engineering, University at Buffalo, Buffalo, New York, USA.
Pedro LeiDepartment of Chemical and Biological Engineering, University at Buffalo, Buffalo, New York, USA.
John ToftegaardDepartment of Biomedical Engineering, University at Buffalo, Buffalo, New York, USA.
Debanik ChoudhuryDepartment of Chemical and Biological Engineering, University at Buffalo, Buffalo, New York, USA.
Maryam ElsayedDepartment of Chemical and Biological Engineering, University at Buffalo, Buffalo, New York, USA.
Yali ZhangDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
Jianmin WangDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
Shweta ChitkaraDepartment of Chemistry, University at Buffalo, Buffalo, New York, USA.
G Ekin Atilla-GokcumenDepartment of Chemistry, University at Buffalo, Buffalo, New York, USA.
Song LiuDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
Stelios T AndreadisDepartment of Chemical and Biological Engineering, University at Buffalo, Buffalo, New York, USA.

Funding

NIH HHS R01AG068250
6 · The paper itself

Abstract

Skeletal muscle aging is associated with increased lipid accumulation, or myosteatosis, leading to lipotoxicity and loss of muscle function. Here, we report that loss of the lactate receptor GPR81 in cellular and progeroid models of muscle aging is associated with impaired lipid oxidation and enhanced lipid accumulation. Knockdown of GPR81 in young healthy myoblasts led to an increase in senescence hallmarks such as DNA damage, accumulation of reactive oxygen species (ROS), impaired mitochondrial activity, and autophagy. Conversely, treatment of senescent myoblasts with GPR81 agonists enhanced lipid oxidation, leading to a decrease in lipid accumulation, ultimately resulting in decreased DNA damage, ROS accumulation, and enhanced ability to form myotubes. In agreement with our in vitro findings, we observed significant improvement in muscle regeneration and overall health of progeric mice that were treated with GPR81 agonists. Our findings suggest that GPR81 plays a key role in skeletal muscle lipid metabolism, and agonists of GPR81 might play a promising role in reversing age-associated lipid accumulation and loss of muscle function.

Indexed as

AgingCellular SenescenceMuscle, SkeletalReceptors, G-Protein-CoupledAnimalsHumansLipid MetabolismMiceReactive Oxygen SpeciesHcar1 protein, mouseReactive Oxygen SpeciesReceptors, G-Protein-Coupledaginglipidsmetabolismmitochondriasarcopeniaskeletal muscle

Identifiers

PMID42542973
PMCPMC13429102

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.