The frailty index outperforms DNA methylation age and its derivatives as an indicator of biological age
The measurement of biological age, as opposed to chronological age, is important to allow the study of factors that are responsible for the heterogeneity in the decline in health and function ability among individuals during aging. Various measures of biological aging have been proposed. Frailty indices based on health deficits in diverse body systems have been well studied, and we have documented the use of a frailty index (FI34) composed of 34 health items, for measuring biological age.
Any useful measure of biological age must predict survival better than chronological age does. Meta-analyses indicate that age acceleration difference and age acceleration residual are significant predictors of mortality, qualifying them as indicators of biological age.
In the presence of chronological age as a covariate, FI34 was a significant predictor of mortality, whereas none of the DNA methylation age-based metrics were. The outperformance of FI34 over DNA methylation age measures was apparent when FI34 and each of the DNA methylation age measures were used together as explanatory variables, along with chronological age: FI34 remained significant but the DNA methylation measures did not. These results indicate that FI34 is a robust predictor of biological age, while these DNA methylation measures are largely a statistical reflection of the passage of chronological time.
The term biological aging has been developed to conceptualize the fact that individuals differ in their manifestation of age changes as they age chronologically.
FI34 increases exponentially with age, indicating declining health and function ability. The rate of increase accelerates approximately 2~3 % annually.
A survival analysis indicates that FI34 predicts mortality better than does chronological age.
The fact that FI34 predicts mortality/survival better than does the simple passage of time indicates that it is more than a naive chronometer. Rather, it is a metric of biological age.
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DNAmAge is highly correlated with chronological age. DNAmAge, and FI34 are unrelated. AgeDiff and AgeResid were not correlated with FI34.
FI34 is a much more robust predictor of survival and measure of biological age than any of the DNAmAge measures proposed thus far. This is because it assesses biological factors that have large effects on survival.
The older you are, the more accurate is FI34 as a predictor of survival.