Age-related cognitive decline and neurodegenerative diseases are a growing concern for society in general. Accumulation of DNA damage is thought to contribute to these impairments, but direct proof that DNA damage results in impaired neuronal plasticity and memory is lacking. In this report, Borgesius and coworkers studied mutant mice impaired in DNA nucleotide excision repair, interstrand crosslink repair, and double-strand break repair. They found that these mice exhibit an age-dependent decrease in neuronal plasticity and progressive neuronal pathology, suggestive of neurodegenerative processes. A similar phenotype was observed in mice where the mutation was restricted to excitatory forebrain neurons. These neuron-specific mutants also developed learning impairments. The authors suggest a causal relationship between unrepaired, accumulating DNA damage, and age-dependent cognitive decline and neurodegeneration.
Borgesius NZ et al., Accelerated Age-Related Cognitive Decline and Neurodegeneration, Caused by Deficient DNA Repair. J. Neuroscience 31: 12543-12553 (2011).
http://www.jneurosci.org/content/31/35/12543.abstract?etoc