Assessing biological aging: the origin of deficit accumulation

Arnold Mitnitski,Kenneth Rockwood,Xiaowei Song

doi:10.1007/s10522-013-9446-3

Arnold Mitnitski, Kenneth Rockwood + Show 1 more

Open Access

https://doi.org/10.1007/s10522-013-9446-3

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Abstract

The health of individuals is highly heterogeneous, as is the rate at which they age. To account for such heterogeneity, we have suggested that an individual’s health status can be represented by the number of health deficits (broadly defined by biological and clinical characteristics) that they accumulate. This allows health to be expressed in a single number: the frailty index (FI) is the ratio of the deficits present in a person to the total number of deficits considered (e.g. in a given database or experimental procedure). Changes in the FI characterize the rate of individual aging. The behavior of the FI is highly characteristic: it shows an age specific, nonlinear increase, (similar to Gompertz law), higher values in females, strong associations with adverse outcomes (e.g., mortality), and a universal limit to its increase (at FI ~0.7). These features have been demonstrated in dozens of studies. Even so, little is known about the origin of deficit accumulation. Here, we apply a stochastic dynamics framework to illustrate that the average number of deficits present in an individual is the product of the average intensity of the environmental stresses and the average recovery time. The age-associated increase in recovery time results in the accumulation of deficits. This not only explains why the number of deficits can be used to estimate individual differences in aging rates, but also suggests that targeting the recovery rate (e.g. by preventive or therapeutic interventions) will decrease the number of deficits that individuals accumulate and thereby benefit life expectancy.Electronic supplementary materialThe online version of this article (doi:10.1007/s10522-013-9446-3) contains supplementary material, which is available to authorized users.

Highlights

Aging is a complex phenomenon but even so shows remarkable regularities in such characteristics as survival probability and mortality rates
The frailty index (FI), has been used to incorporate a range of health deficits that people accumulate during their life course (Mitnitski et al 2001; Kulminski et al 2007; Yashin et al 2007a)
Reformulating Little’s Law in terms of our setting, we suggest that the average number of deficits present in an individual (L) equals the rate of environmental stresses k, times the average recovery time W

Summary

Introduction

Aging is a complex phenomenon but even so shows remarkable regularities in such characteristics as survival probability and mortality rates. We show that the age-associated decline in the recovery rate (or the associated increase in the average time of recovery) together with the stochastic nature of environmental challenges explain the major patterns of deficits accumulation which all groups have observed across the life course. Even knowing one parameter may help to estimate the second one under the conditions that the third parameter does not change It suggests that even if during the life course the intensity of the environmental stresses remained constant, the average recovery time would still increase with age. The fitting function for the older individuals (the solid line) is well represented by the gamma density function, as is described in ‘‘heavy traffic’’ queuing models (Kyprianou 1972)

Discussion

Conclusions