TY - JOUR
T1 - Determinants of rodent longevity in the chaperone-protein degradation network
AU - Rodriguez, Karl A.
AU - Valentine, Joseph M.
AU - Kramer, David A.
AU - Gelfond, Jonathan A.
AU - Kristan, Deborah M.
AU - Nevo, Eviatar
AU - Buffenstein, Rochelle
N1 - Publisher Copyright:
© 2016, Cell Stress Society International.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
KW - Aging
KW - Chaperones
KW - Naked mole rat
KW - Proteasome
KW - Proteostasis
UR - http://www.scopus.com/inward/record.url?scp=84958764883&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84958764883&partnerID=8YFLogxK
U2 - 10.1007/s12192-016-0672-x
DO - 10.1007/s12192-016-0672-x
M3 - Article
C2 - 26894765
AN - SCOPUS:84958764883
SN - 1355-8145
VL - 21
SP - 453
EP - 466
JO - Cell Stress and Chaperones
JF - Cell Stress and Chaperones
IS - 3
ER -