Accelerated Epigenetic Aging Correlates with Later Loss of Memory Function
Aging clocks have yet to fulfill their promise, which is to produce a robust measure of biological aging that can be used to rapidly assess the results of potential therapies to slow or reverse the progression of aging, such as via repair of underlying cell and tissue damage that causes aging. This is because these clocks are produced by machine learning approaches applied to data from a patient population, such as omics data, that changes with age. Exactly why any specific combinations of measures identified in this way, such as the state of DNA methylation at scores of specific CpG sites on the nuclear genome in the case of epigenetic clocks, can predict age or mortality risk is a mystery. There is no way at present to connect a given CpG site or protein expression level or feature in imaging data to what is known of mechanisms of aging. Thus a clock cannot be trusted to assess a new approach to treating aging without calibrating it against that approach in slow, expensive life span studies. Which defeats the point of the exercise.
One of the ways in which researchers approach this challenge is to gathering as much data as possible for as many clocks as possible, in a search for patterns and understanding that will allow clocks to be better trusted. Prospective memory is the ability to remember to follow through on a previously made plan. Like all forms of memory function, it declines with age as the mechanisms of aging produce progressively greater neurodegeneration in brain tissue. In today's open access paper, researchers report on correlations in existing data between epigenetic age acceleration measured in the 40s and prospective memory dysfunction a decade later. The study wasn't large enough and the approach used to assess memory dysfunction was not robust enough to detect correlations at a given age between epigenetic age acceleration and memory function at that time. This suggests that early midlife is an important foundation for later health.
DNA methylation algorithms, such as DunedinPACE, are increasingly used to study the mechanisms of aging and to identify associations with risk factors in adult development and aging. Growing evidence suggests that an increased pace of epigenetic aging is associated with cognitive impairment and dementia, but the correlation between epigenetic aging and subjective cognitive complaints (eg, forgetting a name or forgetting to take your medication), an early marker of dementia risk, remains unexplored.
Using data from The National Study of Daily Experiences (NSDE) and Midlife in the United States (MIDUS; N = 232), we examined the relationship between epigenetic aging rate (ie, DunedinPACE) and self-reported daily memory lapses (ie, occurrence, irritation, interference) in midlife and older adults. We found no significant main effects of the rate of epigenetic aging on self-reported memory lapses; however, a significant chronological age interaction indicates that among the comparatively younger adults in the sample (age 40-49), faster than average rates of aging (ie, higher DunedinPACE) were associated with more prospective memory lapses approximately a decade later as well as greater reports of prospective memory lapse irritation and interference. Additionally, for respondents in their forties, a higher DunedinPACE was associated with both greater prospective memory lapse irritation and interference.
These results suggest that early midlife may be a sensitive period during which the rate of epigenetic aging is more influential on cognitive health outcomes.