Determinants of rodent longevity in the chaperone-protein degradation network

Karl A. Rodriguez; Joseph M. Valentine; David A. Kramer; Jonathan A. Gelfond; Deborah M. Kristan; Eviatar Nevo; Rochelle Buffenstein

doi:10.1007/s12192-016-0672-x

Determinants of rodent longevity in the chaperone-protein degradation network

Karl A. Rodriguez, Joseph M. Valentine, David A. Kramer, Jonathan A. Gelfond, Deborah M. Kristan, Eviatar Nevo, Rochelle Buffenstein

Department of Evolutionary and Environmental Biology

Research output: Contribution to journal › Article › peer-review

Abstract

Proteostasis is an integral component of healthy aging, ensuring maintenance of protein structural and functional integrity with concomitant impact upon health span and longevity. In most metazoans, increasing age is accompanied by a decline in protein quality control resulting in the accrual of damaged, self-aggregating cytotoxic proteins. A notable exception to this trend is observed in the longest-lived rodent, the naked mole-rat (NMR, Heterocephalus glaber) which maintains proteostasis and proteasome-mediated degradation and autophagy during aging. We hypothesized that high levels of the proteolytic degradation may enable better maintenance of proteostasis during aging contributing to enhanced species maximum lifespan potential (MLSP). We test this by examining proteasome activity, proteasome-related HSPs, the heat-shock factor 1 (HSF1) transcription factor, and several markers of autophagy in the liver and quadriceps muscles of eight rodent species with divergent MLSP. All subterranean-dwelling species had higher levels of proteasome activity and autophagy, possibly linked to having to dig in soils rich in heavy metals and where underground atmospheres have reduced oxygen availability. Even after correcting for phylogenetic relatedness, a significant (p < 0.02) positive correlation between MLSP, HSP25, HSF1, proteasome activity, and autophagy-related protein 12 (ATG12) was observed, suggesting that the proteolytic degradation machinery and maintenance of protein quality play a pivotal role in species longevity among rodents.

Original language	English
Pages (from-to)	453-466
Number of pages	14
Journal	Cell Stress and Chaperones
Volume	21
Issue number	3
DOIs	https://doi.org/10.1007/s12192-016-0672-x
State	Published - 1 May 2016

Bibliographical note

Funding Information:
We thank Megan Smith, Vivian Cerritos, and Lillian Cerritos for the excellent care of the naked mole-rat and Damaraland mole-rat colonies. This work was supported by grants from the American Federation for Aging Research (AFAR), the Glenn Foundation for Medical Research, and the NIH/National Institute on Aging (NIA R21 AG043912-01A1) (R.B.). K.A.R. was supported by NIA training grant T32 AG021890 and an AFAR postdoctoral fellowship and now by a K99/R00 Pathway to Independence Award (AG049940-01A1) from the NIA. The comparative biology core of the Nathan Shock Center (UTHSCSA) and the Glen foundation partially contributed to the costs associated with animal husbandry.

Funding Information:
We thank Megan Smith, Vivian Cerritos, and Lillian Cerritos for the excellent care of the naked mole-rat and Damaraland mole-rat colonies. This work was supported by grants from the American Federation for Aging Research (AFAR), the Glenn Foundation for Medical Research, and the NIH/National Institute on Aging (NIA R21 AG043912-01A1) (R.B.). K.A.R. was supported by NIA training grant T32 AG021890 and an AFAR postdoctoral fellowship and now by a K99/R00 Pathway to Independence Award (AG049940-01A1) from the NIA. The comparative biology core of the Nathan Shock Center (UTHSCSA) and the Glen foundation partially contributed to the costs associated with animal husbandry.

Publisher Copyright:
© 2016, Cell Stress Society International.

Keywords

Aging
Chaperones
Naked mole rat
Proteasome
Proteostasis

ASJC Scopus subject areas

Biochemistry
Cell Biology

Access to Document

10.1007/s12192-016-0672-x

Cite this

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title = "Determinants of rodent longevity in the chaperone-protein degradation network",

abstract = "Proteostasis is an integral component of healthy aging, ensuring maintenance of protein structural and functional integrity with concomitant impact upon health span and longevity. In most metazoans, increasing age is accompanied by a decline in protein quality control resulting in the accrual of damaged, self-aggregating cytotoxic proteins. A notable exception to this trend is observed in the longest-lived rodent, the naked mole-rat (NMR, Heterocephalus glaber) which maintains proteostasis and proteasome-mediated degradation and autophagy during aging. We hypothesized that high levels of the proteolytic degradation may enable better maintenance of proteostasis during aging contributing to enhanced species maximum lifespan potential (MLSP). We test this by examining proteasome activity, proteasome-related HSPs, the heat-shock factor 1 (HSF1) transcription factor, and several markers of autophagy in the liver and quadriceps muscles of eight rodent species with divergent MLSP. All subterranean-dwelling species had higher levels of proteasome activity and autophagy, possibly linked to having to dig in soils rich in heavy metals and where underground atmospheres have reduced oxygen availability. Even after correcting for phylogenetic relatedness, a significant (p < 0.02) positive correlation between MLSP, HSP25, HSF1, proteasome activity, and autophagy-related protein 12 (ATG12) was observed, suggesting that the proteolytic degradation machinery and maintenance of protein quality play a pivotal role in species longevity among rodents.",

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author = "Rodriguez, {Karl A.} and Valentine, {Joseph M.} and Kramer, {David A.} and Gelfond, {Jonathan A.} and Kristan, {Deborah M.} and Eviatar Nevo and Rochelle Buffenstein",

note = "Funding Information: We thank Megan Smith, Vivian Cerritos, and Lillian Cerritos for the excellent care of the naked mole-rat and Damaraland mole-rat colonies. This work was supported by grants from the American Federation for Aging Research (AFAR), the Glenn Foundation for Medical Research, and the NIH/National Institute on Aging (NIA R21 AG043912-01A1) (R.B.). K.A.R. was supported by NIA training grant T32 AG021890 and an AFAR postdoctoral fellowship and now by a K99/R00 Pathway to Independence Award (AG049940-01A1) from the NIA. The comparative biology core of the Nathan Shock Center (UTHSCSA) and the Glen foundation partially contributed to the costs associated with animal husbandry. Funding Information: We thank Megan Smith, Vivian Cerritos, and Lillian Cerritos for the excellent care of the naked mole-rat and Damaraland mole-rat colonies. This work was supported by grants from the American Federation for Aging Research (AFAR), the Glenn Foundation for Medical Research, and the NIH/National Institute on Aging (NIA R21 AG043912-01A1) (R.B.). K.A.R. was supported by NIA training grant T32 AG021890 and an AFAR postdoctoral fellowship and now by a K99/R00 Pathway to Independence Award (AG049940-01A1) from the NIA. The comparative biology core of the Nathan Shock Center (UTHSCSA) and the Glen foundation partially contributed to the costs associated with animal husbandry. Publisher Copyright: {\textcopyright} 2016, Cell Stress Society International.",

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AU - Gelfond, Jonathan A.

AU - Kristan, Deborah M.

AU - Nevo, Eviatar

AU - Buffenstein, Rochelle

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Determinants of rodent longevity in the chaperone-protein degradation network

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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