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Genetic signature of human longevity in PKC and NF- κB signaling

dc.contributor.authorRyu, Seungjin
dc.contributor.authorHan, Jeehae
dc.contributor.authorNorden‐krichmar, Trina M.
dc.contributor.authorZhang, Quanwei
dc.contributor.authorLee, Seunggeun
dc.contributor.authorZhang, Zhengdong
dc.contributor.authorAtzmon, Gil
dc.contributor.authorNiedernhofer, Laura J.
dc.contributor.authorRobbins, Paul D.
dc.contributor.authorBarzilai, Nir
dc.contributor.authorSchork, Nicholas J.
dc.contributor.authorSuh, Yousin
dc.date.accessioned2021-08-03T18:14:30Z
dc.date.available2022-08-03 14:14:29en
dc.date.available2021-08-03T18:14:30Z
dc.date.issued2021-07
dc.identifier.citationRyu, Seungjin; Han, Jeehae; Norden‐krichmar, Trina M. ; Zhang, Quanwei; Lee, Seunggeun; Zhang, Zhengdong; Atzmon, Gil; Niedernhofer, Laura J.; Robbins, Paul D.; Barzilai, Nir; Schork, Nicholas J.; Suh, Yousin (2021). "Genetic signature of human longevity in PKC and NF- κB signaling." Aging Cell (7): n/a-n/a.
dc.identifier.issn1474-9718
dc.identifier.issn1474-9726
dc.identifier.urihttps://hdl.handle.net/2027.42/168447
dc.description.abstractGene variants associated with longevity are also associated with protection against cognitive decline, dementia and Alzheimer’s disease, suggesting that common physiologic pathways act at the interface of longevity and cognitive function. To test the hypothesis that variants in genes implicated in cognitive function may promote exceptional longevity, we performed a comprehensive 3- stage study to identify functional longevity- associated variants in ~700 candidate genes in up to 450 centenarians and 500 controls by target capture sequencing analysis. We found an enrichment of longevity- associated genes in the nPKC and NF- κB signaling pathways by gene- based association analyses. Functional analysis of the top three gene variants (NFKBIA, CLU, PRKCH) suggests that non- coding variants modulate the expression of cognate genes, thereby reducing signaling through the nPKC and NF- κB. This matches genetic studies in multiple model organisms, suggesting that the evolutionary conservation of reduced PKC and NF- κB signaling pathways in exceptional longevity may include humans.To test the hypothesis that variants in genes implicated in cognitive function may promote exceptional longevity, we performed a 3- stage study to identify functional longevity- associated variants in ~700 candidate genes in up to 450 centenarians and 500 controls by target capture sequencing analysis. We found an enrichment of longevity- associated genes in the nPKC and NF- kB signaling pathways by gene- based association analyses. Functional analysis of the top three gene variants (NFKBIA, CLU, PRKCH) suggests that non- coding variants reduce signaling through the nPKC and NF- kB.
dc.publisherWiley Periodicals, Inc.
dc.subject.otherrare variant
dc.subject.othercentenarian
dc.subject.otherlongevity
dc.subject.otherNF- κB
dc.subject.otherPKC
dc.subject.othergenetic variant
dc.titleGenetic signature of human longevity in PKC and NF- κB signaling
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelMolecular, Cellular and Developmental Biology
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/168447/1/acel13362.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/168447/2/acel13362_am.pdf
dc.identifier.doi10.1111/acel.13362
dc.identifier.sourceAging Cell
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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