Life Extension Factor Klotho Enhances Cognition

Dena B. Dubal, Jennifer S. Yokoyama, Lei Zhu, Lauren Broestl, Kurtresha Worden, Dan Wang, Virginia E. Sturm, Daniel Kim, Eric Klein, Gui Qiu Yu, Kaitlyn Ho, Kirsten E. Eilertson, Lei Yu, Makoto Kuro-o, Philip L. De Jager, Giovanni Coppola, Gary W. Small, David A. Bennett, Joel H. Kramer, Carmela R. AbrahamBruce L. Miller, Lennart Mucke

Research output: Contribution to journalArticle

102 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1065-1076
Number of pages12
JournalCell Reports
Volume7
Issue number4
DOIs
StatePublished - May 22 2014

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Life Expectancy
Cognition
Aging of materials
Learning
Neuronal Plasticity
Long-Term Potentiation
N-Methyl-D-Aspartate Receptors
Transgenic Mice
Alleles
Data storage equipment
Health
Serum
Genes
Plasticity
Cognitive Dysfunction

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Dubal, D. B., Yokoyama, J. S., Zhu, L., Broestl, L., Worden, K., Wang, D., ... Mucke, L. (2014). Life Extension Factor Klotho Enhances Cognition. Cell Reports, 7(4), 1065-1076. https://doi.org/10.1016/j.celrep.2014.03.076

Life Extension Factor Klotho Enhances Cognition. / Dubal, Dena B.; Yokoyama, Jennifer S.; Zhu, Lei; Broestl, Lauren; Worden, Kurtresha; Wang, Dan; Sturm, Virginia E.; Kim, Daniel; Klein, Eric; Yu, Gui Qiu; Ho, Kaitlyn; Eilertson, Kirsten E.; Yu, Lei; Kuro-o, Makoto; De Jager, Philip L.; Coppola, Giovanni; Small, Gary W.; Bennett, David A.; Kramer, Joel H.; Abraham, Carmela R.; Miller, Bruce L.; Mucke, Lennart.

In: Cell Reports, Vol. 7, No. 4, 22.05.2014, p. 1065-1076.

Research output: Contribution to journalArticle

Dubal, DB, Yokoyama, JS, Zhu, L, Broestl, L, Worden, K, Wang, D, Sturm, VE, Kim, D, Klein, E, Yu, GQ, 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 2014, 'Life Extension Factor Klotho Enhances Cognition', Cell Reports, vol. 7, no. 4, pp. 1065-1076. https://doi.org/10.1016/j.celrep.2014.03.076
Dubal DB, Yokoyama JS, Zhu L, Broestl L, Worden K, Wang D et al. Life Extension Factor Klotho Enhances Cognition. Cell Reports. 2014 May 22;7(4):1065-1076. https://doi.org/10.1016/j.celrep.2014.03.076
Dubal, Dena B. ; Yokoyama, Jennifer S. ; Zhu, Lei ; Broestl, Lauren ; Worden, Kurtresha ; Wang, Dan ; Sturm, Virginia E. ; Kim, Daniel ; Klein, Eric ; Yu, Gui Qiu ; Ho, Kaitlyn ; Eilertson, Kirsten E. ; Yu, Lei ; Kuro-o, Makoto ; De Jager, Philip L. ; Coppola, Giovanni ; Small, Gary W. ; Bennett, David A. ; Kramer, Joel H. ; Abraham, Carmela R. ; Miller, Bruce L. ; Mucke, Lennart. / Life Extension Factor Klotho Enhances Cognition. In: Cell Reports. 2014 ; Vol. 7, No. 4. pp. 1065-1076.
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