Attenuation of p38α MAPK stress response signaling delays the in vivo aging of skeletal muscle myofibers and progenitor cells

John Papaconstantinou, Chen Z. Wang, Min Zhang, San Yang, James Deford, Dmitry V. Bulavin, Naseem Ansari

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Functional competence and self-renewal of mammalian skeletal muscle myofibers and progenitor cells declines with age. Progression of the muscle aging phenotype involves the decline of juvenile protective factors i.e., proteins whose beneficial functions translate directly to the quality of life, and self-renewal of progenitor cells. These characteristics occur simultaneously with the age-associated increase of p38α stress response signaling. This suggests that the maintenance of low levels of p38α activity of juvenile tissues may delay or attenuate aging. We used the dominant negative haploinsufficient p38α mouse (DN-p38αAF/+) to demonstrate that in vivo attenuation of p38α activity in the gastrocnemius of the aged mutant delays age-associated processes that include: a) the decline of the juvenile protective factors, BubR1, aldehyde dehydrogenase 1A (ALDH1A1), and aldehyde dehydrogenase 2 (ALDH2); b) attenuated expression of p16Ink4a and p19Arf tumor suppressor genes of the Cdkn2a locus; c) decreased levels of hydroxynonenal protein adducts, expression of COX2 and iNOS; d) decline of the senescent progenitor cell pool level and d) the loss of gastrocnemius muscle mass. We propose that elevated P-p38α activity promotes skeletal muscle aging and that the homeostasis of p38α impacts the maintenance of a beneficial healthspan.

Original languageEnglish (US)
Pages (from-to)718-733
Number of pages16
JournalAging
Volume7
Issue number9
StatePublished - 2015

Fingerprint

p38 Mitogen-Activated Protein Kinases
Muscle Cells
Aldehyde Dehydrogenase
Skeletal Muscle
Stem Cells
Maintenance
Tumor Suppressor Genes
Mental Competency
Proteins
Homeostasis
Quality of Life
Phenotype
Muscles
Protective Factors

Keywords

  • Aging
  • Gastrocnemius
  • Juvenile protective factors
  • Myofibers
  • p38α
  • Progenitor cells

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Attenuation of p38α MAPK stress response signaling delays the in vivo aging of skeletal muscle myofibers and progenitor cells. / Papaconstantinou, John; Wang, Chen Z.; Zhang, Min; Yang, San; Deford, James; Bulavin, Dmitry V.; Ansari, Naseem.

In: Aging, Vol. 7, No. 9, 2015, p. 718-733.

Research output: Contribution to journalArticle

Papaconstantinou, John ; Wang, Chen Z. ; Zhang, Min ; Yang, San ; Deford, James ; Bulavin, Dmitry V. ; Ansari, Naseem. / Attenuation of p38α MAPK stress response signaling delays the in vivo aging of skeletal muscle myofibers and progenitor cells. In: Aging. 2015 ; Vol. 7, No. 9. pp. 718-733.
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