A recent study, published in Neurobiology of Stress, has unveiled a significant connection between the aging of genes and cognitive abilities, shedding light on how our genes may influence brain health in adulthood.
The human brain, a marvel of complexity responsible for our thoughts, memories, and problem-solving capabilities, has long piqued scientific interest regarding its relationship with aging and cognitive function. As individuals age, cognitive abilities tend to decline, but the precise mechanisms behind this process have remained elusive. Previous research suggested a genetic role in cognitive aging, prompting a team of researchers to delve deeper into understanding how epigenetic aging could be linked to cognitive abilities. Epigenetic aging refers to DNA changes over time influenced by environmental factors and lifestyle choices, which can impact how our genes function.
John M. Felt, an assistant research professor at Pennsylvania State University’s Center for Healthy Aging, explained that the study aimed to explore how epigenetic age acceleration could serve as a biomarker for long-term consequences following early-life adversities and as a midlife biomarker for cognitive impairment. The research was driven by the potential to detect advanced aging earlier in life, enabling the development of preventative interventions for those at the greatest risk of advanced aging.
To uncover the link between epigenetic aging and cognitive function, researchers analyzed data from two distinct groups: the Female Growth and Development Study (FGDS) and the Biological Classification of Mental Disorders (BeCOME) cohort. The FGDS cohort, comprising 86 individuals, was initially recruited between ages 6 and 16, with follow-up assessments conducted between ages 29 and 45. The BeCOME cohort included 313 individuals aged 18 to 65, recruited for psychiatric diagnosis evaluations.
Both cohorts underwent comprehensive neurocognitive assessments, which varied in specific tests but covered cognitive domains such as language abilities, memory, reasoning, working memory, processing speed, and attention. Genomic DNA was extracted from whole blood samples collected from participants in both cohorts.
The study found that a two-factor model was suitable for understanding cognitive abilities in both cohorts, with these factors representing general cognitive abilities and speeded cognitive abilities. General cognitive abilities encompass an individual’s overall cognitive capacity, including reasoning, problem-solving, memory, learning, and abstract thinking. Speeded cognitive abilities assess an individual’s ability to perform cognitive tasks quickly and efficiently, often under time constraints.
The study revealed that first-generation epigenetic clocks, the Horvath and Hannum clocks, did not exhibit significant associations with general cognitive abilities in either cohort, suggesting that the rate of epigenetic aging measured by these clocks is not strongly correlated with overall cognitive function. Surprisingly, the Horvath clock showed a significant association with speeded cognitive abilities in the BeCOME cohort, suggesting that epigenetic aging may influence the speed of cognitive task execution, although this association was not statistically significant in the FGDS cohort.
Second-generation epigenetic clocks, GrimAge and PhenoAge, showed different associations. GrimAge acceleration was nearly significantly linked to lower general cognitive abilities in the FGDS cohort but not in the BeCOME cohort. Importantly, GrimAge acceleration was not associated with speeded cognitive abilities in either cohort. These second-generation epigenetic clocks focus on aging-related health issues and mortality, extending beyond chronological age.
The Dunedin Pace of Aging Methylation (DunedinPoAm) Clock, designed to estimate the pace of biological aging in various systems, provided intriguing results. Acceleration of epigenetic age, as measured by the DunedinPoAm clock, was almost significantly associated with lower general cognitive abilities in the FGDS cohort and significantly associated with lower general cognitive abilities in the BeCOME cohort. While this acceleration was not significantly associated with slower speeded cognitive abilities in the FGDS cohort, it was nearly significant in the BeCOME cohort.
The study’s findings suggest that epigenetic age acceleration may be associated with neurocognitive function, although the specific associations depend on the epigenetic clock used and the characteristics of the study cohort.
The study controlled for factors such as childhood maltreatment, psychological trauma, psychiatric diagnoses, and polygenic scores for educational attainment. However, it is essential to recognize that the study relied on peripheral blood to assess epigenetic aging, which may not directly reflect brain aging. Additionally, the study’s cross-sectional nature makes it challenging to determine causality direction.
To gain a deeper understanding of these findings, future research may explore these associations longitudinally, tracking changes in epigenetic age acceleration and cognitive abilities over time. This approach could help elucidate when epigenetic age acceleration might serve as an early indicator of cognitive impairments linked to later-life neurocognitive degeneration.
The research team emphasizes the need for more extensive studies with larger and more diverse samples to confirm and expand upon these findings. Future research should also focus on optimizing epigenetic clocks for biomarkers of neurocognitive function, enhancing their diagnostic and intervention capabilities, particularly for psychiatric and maltreated populations.
While cross-sectional in nature, the study opens the door to further research into the relationship between epigenetic aging and cognitive abilities, offering potential insights into brain health and cognitive function in adulthood.
By Impact Lab