Fight Aging!

Epigenetic clocks are a topic of considerable interest in the research community. They are perhaps the most promising of the present techniques for assessing biological age, the closest to becoming a useful biomarker of aging. Epigenetic clocks are weighted algorithmic combinations of the DNA methylation status of various sites on the genome, reflecting changes that are very similar for everyone, and which map to age with a margin of error of a few years. These changes are likely reactions to the growing damage and dysfunction of aging - and since everyone ages for the same underlying reasons, it makes sense for some of the changes that take place in cellular processes to be much the same for everyone. The initial epigenetic clocks are now being joined by many others, as there are any number of ways in which to create a viable combination of epigenetic marks that reflects aging.

The interesting aspect of an epigenetic age measure is the degree to which it is higher or lower than chronological age for a given individual. Acceleration of epigenetic age, a higher epigenetic age than chronological age, is quite robustly correlated with incidence of many age-related conditions, as well as with mortality risk. If aging is damage, then more damage has the expected outcome. Today's research materials, looking into lung function and epigenetic age, are illustrative of the numerous other correlational studies published in recent years.

The development of biomarkers of aging is an important topic. A low-cost way to quickly and rigorously measure the damage and dysfunction of age would greatly speed up research and development of rpotential rejuvenation therapies. At present, the only rigorous test of an approach to slow or reverse aging (versus treating a specific age-related condition) is a life span study. That is out of the question for human trials, and even in mice running a life span study is an expensive, slow proposition. As a result, researchers are beginning to use epigenetic age assessments in their studies of aging. Unfortunately, these tools are not yet finalized. Because it is unclear as to what exactly causes the characteristic epigenetic changes of age, it is unknown as to how an epigenetic clock will react to any given new class of ejuvenation therapy. The outcome of an assessment isn't yet actionable, whatever the result. The clocks will have to be calibrated and verified alongside rejuvenation therapies as they are developed - the results cannot yet be taken at face value.

Association of adult lung function with accelerated biological aging

Using longitudinal data from two population-based cohorts we have examined the association of lung function with epigenetic aging and shown that lung function is associated with measures of epigenetic age acceleration, particularly in women and with increasing age. Lung function decline is found to be strongly associated with increase in DNA methylation-based lifespan predictors, plasma protein levels, and their related age adjusted measures.

Our findings suggest that lung function is associated with age acceleration in women and particularly in women above age of 50 years. Forced expiratory volume in one second (FEV1) was found to be declining at a rate of 9.5 mL per year of age acceleration using regression between epigenetic and chronological ages (AAres) and 11.3 mL per year of age acceleration using intrinsic epigenetic age acceleration (IEAA). This same trend was observed for forced vital capacity (FVC). This observation was further supported by measures in an older group of women showing a greater effect of age acceleration on lung function decline.

When the association from the repeated measures from two time points was assessed, a marginal association was found in female subjects, showing a 3.94 ml decline in FVC per year of epigenetic age acceleration (AAres). In contrast, while measuring the effect of age acceleration on lung function decline between baseline and follow-up, there were no significant associations, suggesting that decline in lung function is proportional to the overall degree of biological aging.

In conclusion, this study suggests that epigenetic age acceleration is significantly associated with lung function in women older than 50 years. We hypothesised that this could be due to menopause. However, we have observed that menopause has minimal effect and therefore there is possibility of other unknown physiological factors at older age in females mediating the epigenetic age acceleration effect on lung function. While, it is still unknown what exactly epigenetic aging from DNA methylation measures, this study suggests it can be utilised as one of the important factors to assess women's lung health in old age. DNA methylation-based lifespan predictors, such as DNAm GrimAge and plasma protein levels are strongly associated with lung function. Therefore this study suggests that these can be utilised as important factors to assess lung health in adults.