How Lifespan Associated Genes Modulate Aging Changes: Lessons from Analysis of Longitudinal Data

Overview

Journal Front Genet

Date 2013 Jan 25

PMID 23346098

Citations 24

Authors

Anatoliy I Yashin

Konstantin G Arbeev

Deqing Wu

Liubov S Arbeeva

Alexander Kulminski

Igor Akushevich

Irina Culminskaya

Eric Stallard

Svetlana V Ukraintseva

Affiliations

Soon will be listed here.

Abstract

Background And 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.

Data And Method: 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.

Citing Articles

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Association Between Late-Life Weight Change and Dementia: A Population-based Cohort Study.

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Anti-aging interventions affect lifespan variability in sex, strain, diet and drug dependent fashion.

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Predictors and Implications of Accelerated Cognitive Aging.

Levine M, Harrati A, Crimmins E Biodemography Soc Biol. 2019; 64(2):83-101.

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Kulminski A, Loika Y, Culminskaya I, Huang J, Arbeev K, Bagley O Aging Cell. 2018; 18(1):e12869.

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References

Cacciatore F, Mazzella F, Abete P, Viati L, Galizia G, DAmbrosio D . Mortality and heart rate in the elderly: role of cognitive impairment. Exp Aging Res. 2007; 33(2):127-44. DOI: 10.1080/03610730601166372. View

Arbeev K, Ukraintseva S, Kulminski A, Akushevich I, Arbeeva L, Culminskaya I . Effect of the APOE Polymorphism and Age Trajectories of Physiological Variables on Mortality: Application of Genetic Stochastic Process Model of Aging. Scientifica (Cairo). 2013; 2012. PMC: 3653307. DOI: 10.6064/2012/568628. View

Horiuchi S, Finch C, Mesle F, Vallin J . Differential patterns of age-related mortality increase in middle age and old age. J Gerontol A Biol Sci Med Sci. 2003; 58(6):495-507. DOI: 10.1093/gerona/58.6.b495. View

Yashin A, Akushevich I, Arbeev K, Akushevich L, Ukraintseva S, Kulminski A . Insights on aging and exceptional longevity from longitudinal data: novel findings from the Framingham Heart Study. Age (Dordr). 2007; 28(4):363-374. PMC: 1994150. DOI: 10.1007/s11357-006-9023-7. View

McEwen B . Brain on stress: how the social environment gets under the skin. Proc Natl Acad Sci U S A. 2012; 109 Suppl 2:17180-5. PMC: 3477378. DOI: 10.1073/pnas.1121254109. View

Yashin A, Arbeev K, Kulminski A, Akushevich I, Akushevich L, Ukraintseva S . Health decline, aging and mortality: how are they related?. Biogerontology. 2007; 8(3):291-302. PMC: 1995090. DOI: 10.1007/s10522-006-9073-3. View

Yashin A, Arbeev K, Akushevich I, Ukraintseva S, Kulminski A, Arbeeva L . Exceptional survivors have lower age trajectories of blood glucose: lessons from longitudinal data. Biogerontology. 2009; 11(3):257-65. PMC: 3351103. DOI: 10.1007/s10522-009-9243-1. View

Kuzuya M, Enoki H, Iwata M, Hasegawa J, Hirakawa Y . J-shaped relationship between resting pulse rate and all-cause mortality in community-dwelling older people with disabilities. J Am Geriatr Soc. 2008; 56(2):367-8. DOI: 10.1111/j.1532-5415.2007.01512.x. View

Forsen L, Sogaard A, Meyer H, Edna T, Kopjar B . Survival after hip fracture: short- and long-term excess mortality according to age and gender. Osteoporos Int. 1999; 10(1):73-8. DOI: 10.1007/s001980050197. View

10.

Cruickshank J . The J-curve in hypertension. Curr Cardiol Rep. 2003; 5(6):441-52. DOI: 10.1007/s11886-003-0105-1. View

11.

Deelen J, Beekman M, Uh H, Helmer Q, Kuningas M, Christiansen L . Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited. Aging Cell. 2011; 10(4):686-98. PMC: 3193372. DOI: 10.1111/j.1474-9726.2011.00705.x. View

12.

Cruickshank J . Coronary flow reserve and the J curve relation between diastolic blood pressure and myocardial infarction. BMJ. 1988; 297(6658):1227-30. PMC: 1834729. DOI: 10.1136/bmj.297.6658.1227. View

13.

Blauw G, Lagaay A, Knook D, Meinders A, Westendorp R . Total cholesterol and risk of mortality in the oldest old. Lancet. 1997; 350(9085):1119-23. DOI: 10.1016/s0140-6736(97)04430-9. View

14.

Isles C, Hole D . Is there a J curve distribution for diastolic blood pressure?. Clin Exp Hypertens A. 1992; 14(1-2):139-49. DOI: 10.3109/10641969209036177. View

15.

Manolio T, PEARSON T, Wenger N, Barrett-Connor E, Payne G, HARLAN W . Cholesterol and heart disease in older persons and women. Review of an NHLBI workshop. Ann Epidemiol. 1992; 2(1-2):161-76. DOI: 10.1016/1047-2797(92)90051-q. View

16.

Upmeier E, Lavonius S, Lehtonen A, Viitanen M, Isoaho H, Arve S . Serum lipids and their association with mortality in the elderly: a prospective cohort study. Aging Clin Exp Res. 2010; 21(6):424-30. DOI: 10.1007/BF03327441. View

17.

Richmond J, Aharonoff G, Zuckerman J, Koval K . Mortality risk after hip fracture. J Orthop Trauma. 2002; 17(1):53-6. DOI: 10.1097/00005131-200301000-00008. View

18.

Bohm M, Cotton D, Foster L, Custodis F, Laufs U, Sacco R . Impact of resting heart rate on mortality, disability and cognitive decline in patients after ischaemic stroke. Eur Heart J. 2012; 33(22):2804-12. DOI: 10.1093/eurheartj/ehs250. View

19.

Kannel W, Kannel C, Paffenbarger Jr R, Cupples L . Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J. 1987; 113(6):1489-94. DOI: 10.1016/0002-8703(87)90666-1. View

20.

Karlamangla A, Singer B, Reuben D, Seeman T . Increases in serum non-high-density lipoprotein cholesterol may be beneficial in some high-functioning older adults: MacArthur studies of successful aging. J Am Geriatr Soc. 2004; 52(4):487-94. DOI: 10.1111/j.1532-5415.2004.52152.x. View