How lifespan associated genes modulate aging changes: lessons from analysis of longitudinal data

نویسندگان

  • Anatoliy I. Yashin
  • Konstantin G. Arbeev
  • Deqing Wu
  • Liubov S. Arbeeva
  • Alexander Kulminski
  • Igor Akushevich
  • Irina Culminskaya
  • Eric Stallard
  • Svetlana V. Ukraintseva
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Proteomic analysis of age-dependent changes in protein solubility identifies genes that modulate lifespan

While it is generally recognized that misfolding of specific proteins can cause late-onset disease, the contribution of protein aggregation to the normal aging process is less well understood. To address this issue, a mass spectrometry-based proteomic analysis was performed to identify proteins that adopt sodium dodecyl sulfate (SDS)-insoluble conformations during aging in Caenorhabditis elegan...

متن کامل

Aging, Pensions and Long-term Care: What, Why, Who, How?; Comment on “Financing Long-term Care: Lessons From Japan”

Japan has been aging faster than other industrialized nations, and its experience offers useful lessons to others. Japan has been willing to expand its welfare state with a long-term care (LTC) insurance to finance home care and nursing home care for frail elderly. As Ikegami shows, it created new facilities and expanded specialized staffing for home care, developed a c...

متن کامل

Longitudinal RNA-Seq Analysis of Vertebrate Aging Identifies Mitochondrial Complex I as a Small-Molecule-Sensitive Modifier of Lifespan.

Mutations and genetic variability affect gene expression and lifespan, but the impact of variations in gene expression within individuals on their aging-related mortality is poorly understood. We performed a longitudinal study in the short-lived killifish, Nothobranchius furzeri, and correlated quantitative variations in gene expression during early adult life with lifespan. Shorter- and longer...

متن کامل

Aging-related Genes

Genetic factors affect an individual’s maximum possible lifespan. In humans, the average lifespan is about 40 years shorter than the maximum lifespan. Any gene that influences the development of a disease is called a disease-susceptibility gene. The impacts of disease-susceptibility genes on aging and average lifespan would be much stronger than the impacts of aging genes on maximum lifespan. M...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 4  شماره 

صفحات  -

تاریخ انتشار 2013