Chapter 1 - Reliability Theory of Aging and Longevity

To compare 3 methods of describing the frailty of older adults in nursing homes.

Secondary analysis of a prospective cohort study.

Canadian long-term care institutions.

Institutionalized older adults in the second clinical examination cohort of the Canadian Study of Health and Aging (CSHA-2; n = 728).

Frailty was measured using the Cardiovascular Health Survey definition (Frail-CHS); the CSHA- Clinical Frailty Scale (CSHA-CFS) and a frailty index (FI).

The sample was very elderly (87.7 ± 6.7 years), disabled (83%), and showed a high level of mobility impairment (83%). Each frailty measure correlated moderately well with each other (0.61–0.71) and with a disability measure (–0.45 to –0.53) but only weakly with age (0.13–0.19). By each measure, frailty was significantly associated (P < .01) with an increased risk of mortality, disability and cognitive decline. In a model that included both the frailty-CHS definition and the Frailty Index only the latter was associated with a higher risk of mortality (P < .01 for FI, P = .18 for Frail-CHS) and decline in the 3MS (P < .01 for FI, P = .20 for the Frail-CHS definition). Both measures were significantly associated with new onset disability (P < .01). Similar results were found when both the CSHA-CFS and Frailty Index were included in the models. Random combinations of 15 variables used to make up alternate 5-item Frail-CHS definitions showed that any stratification based on 5 variables allowed tertiles of risk to be discriminated.

Frailty is a robust concept and however defined, elderly people who are frail have worse outcomes than those who are not frail. The 3 measures showed varying ability to express grades of frailty.

Key characteristics relating oxidative damage to aging and longevity are reviewed. Available information indicates that the specific composition of tissue macromolecules (proteins, lipids and mitochondrial DNA) in long-lived animal species gives them an intrinsically high resistance to modification that likely contributes to the superior longevity of these species. This is obtained in the case of lipids by decreasing fatty acid unsaturation, and in the proteins by lowering their methionine content. Long-lived animals also show low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, dietary restriction decreases mitochondrial ROS production and oxidative damage to mitochondrial DNA and proteins. These changes are due to the decreased intake of dietary proteins (not of lipids or carbohydrates) of the dietary restricted animals. In turn, these effects of protein restriction seem to be specifically due to the lowered methionine intake of the protein and dietary restricted animals. It is emphasized that both a low rate of generation of endogenous damage and an intrinsically high resistance to modification of tissue macromolecules are key traits of animal longevity.

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.

The online version of this article (doi:10.1007/s10522-013-9446-3) contains supplementary material, which is available to authorized users.