DNA base excision repair gene polymorphisms modulate human cognitive performance and decline during normal life span.

Area of Science:

• Genetics
• Neuroscience
• Aging Research

Background:

• Cognitive performance naturally declines with age.
• DNA repair mechanisms are crucial for maintaining genomic integrity.
• Single nucleotide polymorphisms (SNPs) can alter gene function.

Purpose of the Study:

• To investigate the association between SNPs in DNA base excision repair (BER) genes and cognitive performance in healthy aging.
• To identify specific BER gene variants that may influence cognitive function over time.

Main Methods:

• Examined SNPs in 10 selected BER genes (e.g., hOGG1, APE1, XRCC1) in 712 healthy Norwegian individuals (aged 20-75).
• Assessed cognitive performance using cross-sectional and longitudinal analyses.
• Utilized statistical models incorporating age, APOE, and CHRNA4 status.

Main Results:

• hOGG1(Ser326Cys) and APE1(Gln51His) showed genotype-by-age interactions affecting cognitive function and longitudinal decline.
• Other BER gene polymorphisms (MutYH, PolB, NEIL2) showed associations when considering APOE or CHRNA4.
• The study identified specific SNP frequencies within the studied population.

Conclusions:

• Polymorphisms in BER genes are associated with cognitive performance in healthy aging individuals.
• Certain BER gene variants may modulate the rate of cognitive decline.
• These findings contribute to understanding the genetic basis of cognitive aging.