Lifespan of mice and primates correlates with immunoproteasome expression

Andrew M Pickering, Marcus Lehr, Richard A. Miller

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

There is large variation in lifespan among different species, and there is evidence that modulation of proteasome function may contribute to longevity determination. Comparative biology provides a powerful tool for identifying genes and pathways that control the rate of aging. Here, we evaluated skin-derived fibroblasts and demonstrate that among primate species, longevity correlated with an elevation in proteasomal activity as well as immunoproteasome expression at both the mRNA and protein levels. Immunoproteasome enhancement occurred with a concurrent increase in other elements involved in MHC class I antigen presentation, including β-2 microglobulin, (TAP1), and TAP2. Fibroblasts from long-lived primates also appeared more responsive to IFN-γ than cells from short-lived primate species, and this increase in IFN-γ responsiveness correlated with elevated expression of the IFN-γ receptor protein IFNGR2. Elevation of immunoproteasome and proteasome activity was also observed in the livers of long-lived Snell dwarf mice and in mice exposed to drugs that have been shown to extend lifespan, including rapamycin, 17-α-estradiol, and nordihydroguaiaretic acid. This work suggests that augmented immunoproteasome function may contribute to lifespan differences in mice and among primate species.

Original languageEnglish (US)
Pages (from-to)2059-2068
Number of pages10
JournalJournal of Clinical Investigation
Volume125
Issue number5
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Primates
Proteasome Endopeptidase Complex
Fibroblasts
Masoprocol
Histocompatibility Antigens Class I
Antigen Presentation
Sirolimus
Estradiol
Messenger RNA
Skin
Liver
Pharmaceutical Preparations
Genes
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lifespan of mice and primates correlates with immunoproteasome expression. / Pickering, Andrew M; Lehr, Marcus; Miller, Richard A.

In: Journal of Clinical Investigation, Vol. 125, No. 5, 01.01.2015, p. 2059-2068.

Research output: Contribution to journalArticle

Pickering, Andrew M ; Lehr, Marcus ; Miller, Richard A. / Lifespan of mice and primates correlates with immunoproteasome expression. In: Journal of Clinical Investigation. 2015 ; Vol. 125, No. 5. pp. 2059-2068.
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