Evidence map›Paper›PMID 41283975›Full record

ArticleGeroScience2026

Necroptosis induced by MLKL overexpression in liver triggers cellular senescence and leads to chronic inflammation and fibrosis.

Ramasamy Selvarani, Sunho Lee, Mani Saminathan, Puvarajan Boovalingam, Kavitha Kurup, Kevin Pham, Roman F Wolf, Willard M Freeman, Archana Unnikrishnan, Arlan Richardson

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in GeroScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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.

Ramasamy Selvarani *Biochemistry & Physiology, University of Oklahoma Health Sciences, Oklahoma City, OK, USA.
Sunho Lee *Biochemistry & Physiology, University of Oklahoma Health Sciences, Oklahoma City, OK, USA.
Mani SaminathanICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India.
Puvarajan BoovalingamRegional Research and Educational Centre, TANUVAS, Pudukkottai, Tamilnadu, India.
Kavitha KurupBiochemistry & Physiology, University of Oklahoma Health Sciences, Oklahoma City, OK, USA.
Kevin PhamGenes & Human Disease Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Roman F WolfOklahoma City Veterans Affairs Health Care System, Oklahoma City, OK, USA.
Willard M FreemanBiochemistry & Physiology, University of Oklahoma Health Sciences, Oklahoma City, OK, USA.
Archana UnnikrishnanBiochemistry & Physiology, University of Oklahoma Health Sciences, Oklahoma City, OK, USA.
Arlan RichardsonBiochemistry & Physiology, University of Oklahoma Health Sciences, Oklahoma City, OK, USA. Arlan-richardson@ouhsc.edu.

Funding

Tissue Pathology Shared ResourceP30CA225520 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI ROBERT S. MANNEL · 2018 to 2026
$27.1M
Visualizing insulin actions on neuronal metabolism and function using fluorescent biosensorsP20GM125528 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Sreemathi Logan · 2019 to 2026
$17.8M
Mentoring Translational Cancer Research in OklahomaP30GM154635 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Rajagopal Ramesh · 2024 to 2026
$4.3M
Role of DNA Methylation in Dietary Restriction mediated insulin sensitivityK01AG056655 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI UNNIKRISHNAN, ARCHANA · 2018 to 2022
$653k
BLRD VA I01 BX004538BLRD VA I01 BX007006BLRD VA IK6 BX005238BLRD VA IK6 BX006033NCI NIH HHS P30 CA225520NIA NIH HHS K01 AG056655NIGMS NIH HHS P20 GM125528NIGMS NIH HHS P30 GM154635U.S. Department of Veterans Affairs 1IK6BX005238U.S. Department of Veterans Affairs IK6BX006033
6 · The paper itself

Abstract

Cellular senescence and necroptosis are two cell fates, which trigger an inflammatory response and increase with age, that have been proposed to play a role in inflammaging. In this study, we performed the first study to directly test the possible interaction between necroptosis and cellular senescence. Using a novel Mlkl-KI mouse model, we were able to specifically induce (~ 4-fold) the overexpression of MLKL, the necroptotic executioner, in hepatocytes (hMlkl-KI mice). The overexpression of MLKL led to increased necroptosis and cell damage/death in liver, as shown by increased levels of MLKL-oligomers, TUNEL staining, and Ki-67 staining in the livers, as well as increased ALT activity and HMGB1 levels in the plasma. The increase in necroptosis was paralleled by an increase in cellular senescence. We observed increased levels of p16

Indexed as

Cellular SenescenceInflammationLiverLiver CirrhosisNecroptosisProtein KinasesAnimalsDisease Models, AnimalHepatocytesMaleMiceMLKL protein, mouseProtein KinasesCellular senescenceChronic inflammationFibrosisInflammagingMLKLNecroptosis

Identifiers

PMID41283975
PMCPMC12972278

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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 OpenQuestion graph.