PMID- 26248058 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230816 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1852 IP - 10 Pt A DP - 2015 Oct TI - Age-related changes in the proteostasis network in the brain of the naked mole-rat: Implications promoting healthy longevity. PG - 2213-24 LID - S0925-4439(15)00223-9 [pii] LID - 10.1016/j.bbadis.2015.08.002 [doi] AB - The naked mole-rat (NMR) is the longest-lived rodent and possesses several exceptional traits: marked cancer resistance, negligible senescence, prolonged genomic integrity, pronounced proteostasis, and a sustained health span. The underlying molecular mechanisms that contribute to these extraordinary attributes are currently under investigation to gain insights that may conceivably promote and extend human health span and lifespan. The ubiquitin-proteasome and autophagy-lysosomal systems play a vital role in eliminating cellular detritus to maintain proteostasis and have been previously shown to be more robust in NMRs when compared with shorter-lived rodents. Using a 2-D PAGE proteomics approach, differential expression and phosphorylation levels of proteins involved in proteostasis networks were evaluated in the brains of NMRs in an age-dependent manner. We identified 9 proteins with significantly altered levels and/or phosphorylation states that have key roles involved in proteostasis networks. To further investigate the possible role that autophagy may play in maintaining cellular proteostasis, we examined aspects of the PI3K/Akt/mammalian target of rapamycin (mTOR) axis as well as levels of Beclin-1, LC3-I, and LC3-II in the brain of the NMR as a function of age. Together, these results show that NMRs maintain high levels of autophagy throughout the majority of their lifespan and may contribute to the extraordinary health span of these rodents. The potential of augmenting human health span via activating the proteostasis network will require further studies. CI - Copyright (c) 2015. Published by Elsevier B.V. FAU - Triplett, Judy C AU - Triplett JC AD - Department of Chemistry, University of Kentucky, Lexington, KY 40506, United States. FAU - Tramutola, Antonella AU - Tramutola A AD - Department of Biochemical Sciences, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy. FAU - Swomley, Aaron AU - Swomley A AD - Department of Chemistry, University of Kentucky, Lexington, KY 40506, United States. FAU - Kirk, Jessime AU - Kirk J AD - Department of Chemistry, University of Kentucky, Lexington, KY 40506, United States. FAU - Grimes, Kelly AU - Grimes K AD - Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78245, United States; Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78245, United States. FAU - Lewis, Kaitilyn AU - Lewis K AD - Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78245, United States; Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78245, United States. FAU - Orr, Miranda AU - Orr M AD - Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78245, United States; Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78245, United States. FAU - Rodriguez, Karl AU - Rodriguez K AD - Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78245, United States; Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78245, United States. FAU - Cai, Jian AU - Cai J AD - Department of Nephrology and Proteomics Center, University of Louisville, Louisville, KY 40202, United States. FAU - Klein, Jon B AU - Klein JB AD - Department of Nephrology and Proteomics Center, University of Louisville, Louisville, KY 40202, United States. FAU - Perluigi, Marzia AU - Perluigi M AD - Department of Biochemical Sciences, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy. FAU - Buffenstein, Rochelle AU - Buffenstein R AD - Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78245, United States; Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78245, United States. Electronic address: Buffenstein@UTHSCSA.edu. FAU - Butterfield, D Allan AU - Butterfield DA AD - Department of Chemistry, University of Kentucky, Lexington, KY 40506, United States; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, United States. Electronic address: dabcns@uky.edu. LA - eng GR - I01 BX002211/BX/BLRD VA/United States GR - K99 AG049940/AG/NIA NIH HHS/United States GR - RF1 AG068283/AG/NIA NIH HHS/United States GR - T32 AG021890/AG/NIA NIH HHS/United States PT - Journal Article DEP - 20150804 PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 SB - IM PMC - PMC4845741 MID - NIHMS776570 OTO - NOTNLM OT - Aging OT - Naked mole-rat OT - Phosphoproteomics OT - Proteomics OT - Proteostasis networks OT - mTOR EDAT- 2015/08/08 06:00 MHDA- 2015/08/08 06:01 PMCR- 2016/04/26 CRDT- 2015/08/07 06:00 PHST- 2015/04/27 00:00 [received] PHST- 2015/07/13 00:00 [revised] PHST- 2015/08/01 00:00 [accepted] PHST- 2015/08/07 06:00 [entrez] PHST- 2015/08/08 06:00 [pubmed] PHST- 2015/08/08 06:01 [medline] PHST- 2016/04/26 00:00 [pmc-release] AID - S0925-4439(15)00223-9 [pii] AID - 10.1016/j.bbadis.2015.08.002 [doi] PST - ppublish SO - Biochim Biophys Acta. 2015 Oct;1852(10 Pt A):2213-24. doi: 10.1016/j.bbadis.2015.08.002. Epub 2015 Aug 4.