Proceedings of the National Academy of Sciences of the United States of America
Telomere length in humans is emerging as a biomarker of aging because its shortening is associated with aging-related diseases and early mortality. However, genetic mechanisms responsible for these associations are not known. Here, in a cohort of Ashkenazi Jewish centenarians, their offspring, and offspring-matched controls, we studied the inheritance and maintenance of telomere length and variations in two major genes associated with telomerase enzyme activity, hTERT and hTERC.
BACKGROUND: Physical activity is associated with reduced risks of chronic diseases and premature death. Whether physical activity is also associated with improved overall health among those who survive to older ages is unclear. METHODS: A total of 13,535 Nurses' Health Study participants who were free of major chronic diseases at baseline in 1986 and had survived to age 70 years or older as of the 1995-2001 period made up the study population.
OBJECTIVES: To explore measures of metabolic syndrome and glucose metabolism in families with exceptional longevity. DESIGN: Case-control study. SETTING: A university hospital in Leiden, the Netherlands. PARTICIPANTS: One hundred twenty-one offspring of nonagenarian siblings, who were enriched for familial factors promoting longevity, and 113 of their partners. No subject had diabetes mellitus. MEASUREMENTS: Prevalence of metabolic syndrome was determined according to the criteria of the Third Report of the National Cholesterol Education Program.
Proceedings of the National Academy of Sciences of the United States of America
In the first paper to present formal theory explaining that senescence is a consequence of natural selection, W. D. Hamilton concluded that human postmenopausal longevity results from the contributions of ancestral grandmothers to the reproduction of their relatives. A grandmother hypothesis, subsequently elaborated with additional lines of evidence, helps explain both exceptional longevity and additional features of life history that distinguish humans from the other great apes.
The search for longevity-determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity.
The Journal of Clinical Endocrinology and Metabolism
CONTEXT: Few studies have examined whether the inflammatory markers IL-6 and C-reactive protein (CRP) are associated with exceptional longevity. OBJECTIVE: Our objective was to determine the association of serum CRP and IL-6 with adult lifespan. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective, population-based study of 610 men and 743 postmenopausal women, mean age 73 yr, who had serum IL-6 and CRP measurements at baseline (1984-1987) and who were followed for mortality for up to 23 yr (through 2008).
The PTPN22 gene, located on chromosome 1p13, encoding lymphoid protein tyrosine phosphatase (LYP), plays a crucial role in the negative control of T lymphocyte activation. Since the age-related change in T-cell signal transduction may be one of the most important causes of cell-mediated immune response decline with ageing, we performed a population-based association study to test whether the PTPN22 1858C>T (R620W) functional polymorphism affects the ability to survive to old age and to reach even exceptional life expectancy.
Individuals from families recruited for the Long Life Family Study (LLFS) (n= 4559) were examined and compared to individuals from other cohorts to determine whether the recruitment targeting longevity resulted in a cohort of individuals with better health and function. Other cohorts with similar data included the Cardiovascular Health Study, the Framingham Heart Study, and the New England Centenarian Study. Diabetes, chronic pulmonary disease and peripheral artery disease tended to be less common in LLFS probands and offspring compared to similar aged persons in the other cohorts.
The authors investigated whether cognitive function may be used as an endophenotype for longevity by assessing the cognitive performance of a family-based cohort consisting of 1380 individuals from 283 families recruited for exceptional survival in field centers in Boston, New York, Pittsburgh, and Denmark. Cognitive performance was assessed in the combined offspring of the Long Life Family Study (LLFS) probands and their LLFS siblings as compared with their spouses' cognitive performance.
Low handgrip strength has been linked with premature mortality in diverse samples of middle-aged and elderly subjects. The value of handgrip strength as marker of "exceptional" human longevity has not been previously explored. We postulated that the genetic influence on extreme survival might also be involved in the muscular strength determination pathway. Therefore, the objective of this study was to assess the muscle strength in a sample of middle-aged adults who are genetically enriched for exceptional survival and comparing them to a control group.
