Loss of Lung Function Correlates with Epigenetic Age Acceleration
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.
Hi there! Just a 2 cents. We Need Thems therapy by 2030. Tops. (Crossing (them) fingers, but not so hard). Who wants to be in 2040ish and still jack - we Have to Start Being on the therapies or we will never Reverse (All) the damages enough/too late (for us mid-old/mid-young people).
Hoping 2020, is truly 20/20 (20 out of 20 = 100% score, result). It is like in 2000. We had to defeat the 2000 bug, now, in 2020 we have to defeat the 2020 aging bug.
'' 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. ''
As you said Reason, the largest contributor to these characteristic epigenetic changes of age, are the damages incured of normal metabolism (unflawless/unperfect/can mutate/delete/faulty -> vicious circle -> more (piling/unrepaired/irreversible) damage -> aging (manifested/readable as epigenetic drifting/changes; the cause is mainly the damage and visual result is the epigenomic homeostatic loss; in other words, General (Deleterious/Inflammatory/Oncogenic) Gene Silencing -> General (Deleterious/Inflammatory/Oncogenic) Gene Unsilencing). As we age we 'activate' this orchestrated auto-destruction - in order to avoid cancer/cell overtaking. Evolution weighed the benefits vs. non-benefits for our complex bodies; and decided it was better to 'end us' (mort*lity/avoid cancer spread) than 'not end us' (immort*ality/mutations long term/cancer spread). When I look at Hydras, an imm*rtal uncomplex animal that does not suffer of cancer (or rarely), yet is 100% full of telomerase in its germ cells; then Something is going on.
That's where I Wonder about WILT and such therapies that want to remove telomerase; albeit, in cancer cells, it's a pretty safe bet to destroy them. Our telomeres can NOT shrinken forever. Either get cancer or we die of aging/short telomeres. They are our replicative/cell cycle counters and cancer breaks pedal. High telomeres = oncogenic silence (in general, though mutations can happen faster cell dynamics; it's why people with high telomeres have higher Nevi (moles) count, like I have moles/nevis on my back, this is a tell-tale sign that the person has taller telomeres whereas people with less moles have Higher Oncogene activation/more ox. stress (since ROS from oncogenes destroy tumor cells) and thus, less moles, that is, Until they have more (whence the cancer takes over...that is where skin moles/mutations can turn from bening to malign/cancerous). Many skin/dermatological showed that there is crossplay between too little or too much of telomerase/telomeres; lke cancer is at the crossraod of it. Because oncogenes and deleterious mutations acquiry from exposure to oxidative stress damaging DNA conditions (such as UV rays exposure/Radiation causing cancer in skin from all the destruction of fibroblast/ECM/mitochondrial DNA and nuclear DNA; which means telomeric DDR -> DNA damage/DSBs/SSBs -> epigenetic drifting and oncogenic activation to destroy '(in)coming cancer').
''...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.''
Had same thought, menopause. Dramatic cause of such. 'minimal effect' is wrong, it is not minimal at all. Menopause is one largest contributor had that later mid-age (50s+) time period.
If you don't activate/do exercice change diet or have sex, it's bad news/the old 'Use it or Lose it' applies. It is because menopause (and andropause in men) is accompanied by reduction of oestrogen (hormonal) activation of telomerase (oestrogenic recepetors that are direct acitvators of telomerase protection). Thus, hormonal protection in women is lost at that time, and thus, become like men, in a sense, 'Faster aging/faster accumulation of damage'. Because for men, testosterone must be converted to estrogen to Obtain telomerase protection, in men; in women, by then, the hormonal changes become (seriously) deleterious and thus, faster aging by loss of telomerase 'boost' of 'youth'.
''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''
Damages. The sum of them, mostly, irreversible and thus, measure the Total Advancement so far (towards death). It also measure the replicative advancement (hayflick) indirectly/telomeres (because epiclock and telomerase talk to each toher).
Just a 2 cents.
Would inspiratory/expiratory muscle training help in any way with this? I have "the breather" from Amazon which exercises lungs and I always notice that whenever I do it, exercise feels easier.
@Nate
I woke say that many breathing exercises would help. If course the caveat about correlation vs causation always applies. As for the done, I think I saw a research that showed improvement of athletes using a breathing exercise device that required effort to inhale. Your milage will vary ...