Skip to content
DraconiticResearch
Search Sources API
197,768 studies31 sourcesUpdated 5 min ago
Peer-reviewedCC BY 4.0Aging Cell

MKP‐2 Genetic Depletion Modulates Adipose Lipid Composition, Cellular Senescence, and Aging in Mice

  • Morgan Welch1
  • Nabin Ghimire1
  • Shauri Smith1
  • Cassandra Secunda1
  • Alexis Fink1
  • Alissar Sleiman1
  • Laura Chambliss1
  • Christopher Pinckard1
  • Chloe Reyes1
  • Priya Katta1
  • Anna Ai1
  • Benjamin R. Harrison2
1 more authors
  • Ahmed Lawan1
  1. 1Department of Biological Sciences University of Alabama in Huntsville Huntsville Alabama USA
  2. 2Department of Anesthesiology and Pain Medicine University of Washington Seattle Washington USA
Read full textDOICite

Abstract

Aging is characterized by a gradual decline in physiological functions, impaired cellular repair mechanisms, and increased disease susceptibility. Mitogen‐activated protein kinase phosphatase‐2 (MKP‐2) regulates diverse biological functions, including regulation of infection, brain activity, nutrient metabolism, and cell‐cycle progression, but its role in senescence and adipose lipid metabolism in vivo remains unclear. Here, we investigated the effects of MKP‐2 deficiency on cellular senescence and adipose lipid composition in aged mice using targeted lipidomics. MKP‐2‐deficient mouse embryonic fibroblasts (MEFs) and epididymal white adipose tissue (EWAT) exhibited reduced premature senescence. Lipidomic analysis revealed increased hexosylceramides (HexCERs) and phosphatidylglycerols (PG), and decreased diacylglycerols (DGs) in adipose tissue. These lipid alterations were accompanied by preserved lamin B1, reduced p53 phosphorylation, p16, and PAI‐1, and increased JNK and Akt phosphorylation in EWAT. MKP‐2 deficiency was also associated with extended lifespan and enhanced insulin responsiveness. Together, these studies identify MKP‐2 as a potential regulator linking adipose lipid metabolism, stress‐responsive signaling, cellular senescence, and aging, with its loss promoting a metabolically resilient adipose state that may contribute to improved systemic health and lifespan.

Related

  1. Single-cell multiomic QTL mapping reveals state-dependent genetic regulation and associated gene during cellular senescence
    X. Yi, X. Wang, K. Liu +12
    bioRxivPreprintCC BYFull textGenetics & genomicsbioRxiv
  2. Pharmacological depletion of macrophages leads to a reduction in inflammation and senescence in aged murine kidneys
    Milan R. Stojiljkovic, Christian Schmeer, Otto W. Witte
    ImmunobiologyPeer-reviewedCC BYFull textImmunologyDOAJ
  3. TRPM2-mediated Ca2+ entry drives cellular senescence to irradiation-induced salivary gland dysfunction
    Viktor R. Drel, Shankara N. Varadarajan, Tarek Mohamed Abd El-Aziz +4
    iSciencePeer-reviewedCC BY-NC 4.0Cell biologyCell PressCrossref
  4. Soluble pathogenic tau transmission to astrocytes drives acute oxidative damage, cellular senescence, and neurovascular uncoupling in a model of Alzheimers tauopathy
    V. Galvan, H. makhlouf, l. Miller +8
    bioRxivPreprintAll rights reservedFull textNeurosciencebioRxiv
  5. Senescence-induced cellular reprogramming drives cnidarian whole-body regeneration
    Miguel Salinas-Saavedra, F. Febrimarsa, Gabriel Krasovec +3
    Cell ReportsPeer-reviewedCC BY 4.0Full text45 citedCell biologyDevelopmental biologyHAL

Cite

BibTeXRIS
BibTeX
@article{welch2026mkp2,
  title = {{MKP‐2 Genetic Depletion Modulates Adipose Lipid Composition, Cellular Senescence, and Aging in Mice}},
  author = {Morgan Welch and Nabin Ghimire and Shauri Smith and Cassandra Secunda and Alexis Fink and Alissar Sleiman and Laura Chambliss and Christopher Pinckard and Chloe Reyes and Priya Katta and Anna Ai and Benjamin R. Harrison and Ahmed Lawan},
  journal = {Aging Cell},
  year = {2026},
  month = nov,
  doi = {10.1111/acel.70794},
  url = {https://doi.org/10.1111/acel.70794},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - MKP‐2 Genetic Depletion Modulates Adipose Lipid Composition, Cellular Senescence, and Aging in Mice
AU  - Morgan Welch
AU  - Nabin Ghimire
AU  - Shauri Smith
AU  - Cassandra Secunda
AU  - Alexis Fink
AU  - Alissar Sleiman
AU  - Laura Chambliss
AU  - Christopher Pinckard
AU  - Chloe Reyes
AU  - Priya Katta
AU  - Anna Ai
AU  - Benjamin R. Harrison
AU  - Ahmed Lawan
PY  - 2026
DA  - 2026/11/03
JO  - Aging Cell
DO  - 10.1111/acel.70794
UR  - https://doi.org/10.1111/acel.70794
AB  - Aging is characterized by a gradual decline in physiological functions, impaired cellular repair mechanisms, and increased disease susceptibility. Mitogen‐activated protein kinase phosphatase‐2 (MKP‐2) regulates diverse biological functions, including regulation of infection, brain activity, nutrient metabolism, and cell‐cycle progression, but its role in senescence and adipose lipid metabolism in vivo remains unclear. Here, we investigated the effects of MKP‐2 deficiency on cellular senescence and adipose lipid composition in aged mice using targeted lipidomics. MKP‐2‐deficient mouse embryonic fibroblasts (MEFs) and epididymal white adipose tissue (EWAT) exhibited reduced premature senescence. Lipidomic analysis revealed increased hexosylceramides (HexCERs) and phosphatidylglycerols (PG), and decreased diacylglycerols (DGs) in adipose tissue. These lipid alterations were accompanied by preserved lamin B1, reduced p53 phosphorylation, p16, and PAI‐1, and increased JNK and Akt phosphorylation in EWAT. MKP‐2 deficiency was also associated with extended lifespan and enhanced insulin responsiveness. Together, these studies identify MKP‐2 as a potential regulator linking adipose lipid metabolism, stress‐responsive signaling, cellular senescence, and aging, with its loss promoting a metabolically resilient adipose state that may contribute to improved systemic health and lifespan.
SN  - 1474-9718
SN  - 1474-9726
ER  -