Increased learning and brain long-term potentiation in aged mice lacking DNA polymerase μ.

• Main Authors: Daniel Lucas, José M Delgado-García, Beatriz Escudero, Carmen Albo, Ana Aza, Rebeca Acín-Pérez, Yaima Torres, Paz Moreno, José Antonio Enríquez, Enrique Samper, Luis Blanco, Alfonso Fairén, Antonio Bernad, Agnès Gruart
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2013-01-01
• Series: PLoS ONE
• Online Access: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23301049/pdf/?tool=EBI

A definitive consequence of the aging process is the progressive deterioration of higher cognitive functions. Defects in DNA repair mechanisms mostly result in accelerated aging and reduced brain function. DNA polymerase µ is a novel accessory partner for the non-homologous end-joining DNA repair pathway for double-strand breaks, and its deficiency causes reduced DNA repair. Using associative learning and long-term potentiation experiments, we demonstrate that Polµ(-/-) mice, however, maintain the ability to learn at ages when wild-type mice do not. Expression and biochemical analyses suggest that brain aging is delayed in Polµ(-/-) mice, being associated with a reduced error-prone DNA oxidative repair activity and a more efficient mitochondrial function. This is the first example in which the genetic ablation of a DNA-repair function results in a substantially better maintenance of learning abilities, together with fewer signs of brain aging, in old mice.