How the effects of aging and stresses of life are integrated in mortality rates: insights for genetic studies of human health and longevity

Abstract

Background Increasing proportions of elderly individuals in developed countries combined with substantial increases in related medical expenditures make the improvement of the health of the elderly a high priority today. If the process of aging by individuals is a major cause of age related health declines then postponing aging could be an efficient strategy for improving the health of the elderly. Implementing this strategy requires a better understanding of genetic and non-genetic connections among aging, health, and longevity. Data and methods We review progress and problems in research areas whose development may contribute to analyses of such connections. These include genetic studies of human aging and longevity, the heterogeneity of populations with respect to their susceptibility to disease and death, forces that shape age patterns of human mortality, secular trends in mortality decline, and integrative mortality modeling using longitudinal data. Results The dynamic involvement of genetic factors in (i) morbidity/mortality risks, (ii) responses to stresses of life, (iii) multi-morbidities of many elderly individuals, (iv) trade-offs for diseases, (v) genetic heterogeneity, and (vi) other relevant aging-related health declines, underscores the need for a comprehensive, integrated approach to analyze the genetic connections for all of the above aspects of aging-related changes. Conclusion The dynamic relationships among aging, health, and longevity traits would be better understood if one linked several research fields within one conceptual framework that allowed for efficient analyses of available longitudinal data using the wealth of available knowledge about aging, health, and longevity already accumulated in the research field.

Quantifying Intrinsic and Extrinsic Contributions to Human Longevity: Application of a Two-Process Vitality Model to the Human Mortality Database

“…We suggest that an understanding of historical patterns and projection of future trends requires that researchers consider expected life span in terms of changes in external challenges and internal aging. Indeed, researchers are investigating how genetic and nongenetic changes contribute to aging (Ukraintseva et al 2016; Yashin et al 2016), and research is underway to quantify the linkages among health behavior, environmental conditions, and longevity (Crimmins et al 2010). We suggest that the partition of intrinsic and extrinsic mortalities provides a simple and powerful framework for merging these endeavors.…”

Dynamics of biomarkers in relation to aging and mortality

“…The width of a U-shape (or a J-shape) of mortality as a function of a biomarker can be interpreted in the context of stress resistance (Yashin et al, 2015; Yashin et al, 2012a) or in alternative terms of “vulnerability” (Arbeev et al, 2011). The width of the U-shape can be used to characterize the “robustness”, or “vulnerability,” component of stress resistance.…”

“…If the U-shape narrows (e.g., as the individual ages), an organism becomes more vulnerable to deviations of respective biomarkers from the “normal” values: if the U-shape is narrower then the same magnitude of deviation from the “optimal” value which minimizes hazard results in a larger increase in the risk of death. The SPM allows characterizing this important component of the process of aging (i.e., decline in stress resistance) from available data on longitudinal dynamics of biomarkers and investigate various genetic and non-genetic factors that can affect this decline (Yashin et al, 2015). …”

Insights into mortality patterns and causes of death through a process point of view model

“…diseases, into aggregates: one of sufficient strength to overcome any level of vital power and a second weaker 1 We do note that another significant body of theory links biological processes to mortality but this framework links biological processes directly to the mortality rate and does not track the cumulative effects of processes leading up to mortality (e.g. Yashin et al 2012;Yashin et al 2016;Yashin et al 2000). aggregate in which mortality depends on the remaining vital power. Strehler and Mildvan (1960) mathematically captured the process of mortality as challenges to vital power in terms of the probability of a challenge of random magnitude and frequency exceeding a linearly declining survival capacity, denoted vitality.…”