How lifespan associated genes modulate aging changes: lessons from analysis of longitudinal data.
OBJECTIVE
The influence of genes on human lifespan is mediated by biological processes that characterize body's functioning. The age trajectories of these processes contain important information about mechanisms linking aging, health, and lifespan. The objective of this paper is to investigate regularities of aging changes in different groups of individuals, including individuals with different genetic background, as well as their connections with health and lifespan.


METHODS
To reach this objective we used longitudinal data on four physiological variables, information about health and lifespan collected in the Framingham Heart Study (FHS), data on longevity alleles detected in earlier study, as well as methods of statistical modeling.


RESULTS
We found that phenotypes of exceptional longevity and health are linked to distinct types of changes in physiological indices during aging. We also found that components of aging changes differ in groups of individuals with different genetic background.


CONCLUSIONS
These results suggest that factors responsible for exceptional longevity and health are not necessary the same, and that postponing aging changes is associated with extreme longevity. The genetic factors which increase lifespan are associated with physiological changes typical of healthy and long-living individuals, smaller mortality risks from cancer and CVD and better estimates of adaptive capacity in statistical modeling. This indicates that extreme longevity and health related traits are likely to be less heterogeneous phenotypes than lifespan, and studying these phenotypes separately from lifespan may provide additional information about mechanisms of human aging and its relation to chronic diseases and lifespan.
Center for Population Health and Aging, Duke University Durham, NC, USA.
Anatoliy I
AI
Yashin
Konstantin G
KG
Arbeev
Deqing
D
Wu
Liubov S
LS
Arbeeva
Alexander
A
Kulminski
Igor
I
Akushevich
Irina
I
Culminskaya
Eric
E
Stallard
Svetlana V
SV
Ukraintseva
age trajectories; genetic dose; integrative genetic mortality model; longevity genes; physiological variables