Examination of the Dimensions of Biological Age

Abstract

The concept of biological age has been used more and more frequently in aging research in attempts to measure the progress of the biological aging process as opposed to the simple passage of time. Several approaches to quantify biological age have been utilized, including the use of biomarkers in the form of serum analytes, epigenetic markers, and deficit or frailty indices. Among these methods, the deficit index possesses a theoretical basis grounded in systems biology by incorporating networks, with their emergent properties, to describe the complex aging system. Application of the deficit index in human aging studies points to the increased energetic demands posed by an aging system that is losing integration. Different aspects of mitochondrial function appear to be responsible in males and females. The gut microbiome loses complexity in tandem with the host, as biological age increases, with likely impact on host metabolism and immunity. Specific DNA methylation changes are associated with biological age. They suggest declining connectivity within the aging network, at the cellular level. The deficit/frailty index may account for at least part of the departure at older ages of the observed mortality in the population from the exponential increase modeled by the Gompertz equation.

Keywords: DNA methylation; biological age; complexity; deficit index; frailty index; gut microbiome; healthy aging; network.

FIGURE 1

Cox proportional hazards of death. Censored survival data for 262 subjects aged 60–103 from the Louisiana Healthy Aging Study (LHAS) are presented as Z scores. Age, FI₃₄, DNA methylation age (DNAm Age), Age Acceleration Difference (Age Diff), and Age Acceleration Residual (Age Resid) are included as covariates in the regressions, as indicated. (A) All 262 subjects, (B) nonagenarians only (N = 161). ^∗p < 0.05; ^∗∗p < 0.01; and ^∗∗∗p < 0.001. This figure has been reproduced from Jazwinski and Kim (2017) under the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).

FIGURE 2

Conceptualization of the deficit/frailty index as a network description of a complex aging system. Complexity declines as a function of biological age. The result is loss of components of networks at various levels of organization, leading to weaker integration due to loss of connections. The aging system consists of the host and its gut microbiome, with the epigenome comprising the interface between them. Losses in integrated function of the aging system pose energetic demands to keep it functioning. This results in the increased resting metabolic rate (RMR) associated with progressing biological age. RMR is the energy expenditure for maintenance of basic body functions. It accounts for 60–70% of total daily energy expenditure.