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Cell Rep DOI:10.1016/j.celrep.2014.03.076

Life extension factor klotho enhances cognition.

Publication TypeJournal Article
Year of Publication2014
AuthorsDubal, DB, Yokoyama, JS, Zhu, L, Broestl, L, Worden, K, Wang, D, Sturm, VE, Kim, D, Klein, E, Yu, G-Q, Ho, K, Eilertson, KE, Yu, L, Kuro-o, M, De Jager, PL, Coppola, G, Small, GW, Bennett, DA, Kramer, JH, Abraham, CR, Miller, BL, Mucke, L
JournalCell Rep
Volume7
Issue4
Pages1065-76
Date Published2014 May 22
ISSN2211-1247
KeywordsAge Factors, Aged, Aged, 80 and over, Animals, Cognition, Cohort Studies, Female, Glucuronidase, Humans, Life Expectancy, Male, Memory, Mice, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Receptors, N-Methyl-D-Aspartate, Synapses
Abstract

Aging is the primary risk factor for cognitive decline, an emerging health threat to aging societies worldwide. Whether anti-aging factors such as klotho can counteract cognitive decline is unknown. We show that a lifespan-extending variant of the human KLOTHO gene, KL-VS, is associated with enhanced cognition in heterozygous carriers. Because this allele increased klotho levels in serum, we analyzed transgenic mice with systemic overexpression of klotho. They performed better than controls in multiple tests of learning and memory. Elevating klotho in mice also enhanced long-term potentiation, a form of synaptic plasticity, and enriched synaptic GluN2B, an N-methyl-D-aspartate receptor (NMDAR) subunit with key functions in learning and memory. Blockade of GluN2B abolished klotho-mediated effects. Surprisingly, klotho effects were evident also in young mice and did not correlate with age in humans, suggesting independence from the aging process. Augmenting klotho or its effects may enhance cognition and counteract cognitive deficits at different life stages.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S2211-1247(14)00287-3
DOI10.1016/j.celrep.2014.03.076
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24813892?dopt=Abstract

Alternate JournalCell Rep
PubMed ID24813892
PubMed Central IDPMC4176932
Grant ListP50 AG023501 / AG / NIA NIH HHS / United States
AG025831 / AG / NIA NIH HHS / United States
RR00865 / RR / NCRR NIH HHS / United States
K23 AG040127 / AG / NIA NIH HHS / United States
AG032289 / AG / NIA NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
AG17917 / AG / NIA NIH HHS / United States
AG010435 / AG / NIA NIH HHS / United States
M01 RR000865 / RR / NCRR NIH HHS / United States
R01 AG019712 / AG / NIA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
AG034531 / AG / NIA NIH HHS / United States
P50AG23501 / AG / NIA NIH HHS / United States
P30 NS065780 / NS / NINDS NIH HHS / United States
P01 AG000001 / AG / NIA NIH HHS / United States
P01 AG019724 / AG / NIA NIH HHS / United States
AG15819 / AG / NIA NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
R01 AG018440 / AG / NIA NIH HHS / United States
AG00001 / AG / NIA NIH HHS / United States
R37 AG018440 / AG / NIA NIH HHS / United States
P01 AG010435 / AG / NIA NIH HHS / United States
AG022074 / AG / NIA NIH HHS / United States
AG019712 / AG / NIA NIH HHS / United States
AG18440 / AG / NIA NIH HHS / United States
R01 AG032289 / AG / NIA NIH HHS / United States
P01 AG022074 / AG / NIA NIH HHS / United States
K08 AG034531 / AG / NIA NIH HHS / United States
RR18938-01 / RR / NCRR NIH HHS / United States
NS065780 / NS / NINDS NIH HHS / United States
AG19724 / AG / NIA NIH HHS / United States
R01 AG015819 / AG / NIA NIH HHS / United States
P01 AG025831 / AG / NIA NIH HHS / United States