Adult

OBJECTIVES: To assess the cause of death for centenarians' offspring and controls. DESIGN: Cross-sectional study. SETTING: Community-based, nationwide sample. PARTICIPANTS: Family pedigree information was collected on 295 offspring of centenarians (from 106 families with a parent already enrolled in the nationwide New England Centenarian Study) and on 276 controls (from 82 control families) from 1997 to 2000. Controls were individuals whose parents were born in the same year as the centenarians but at least one of whom died at the average life expectancy.

Recently, chromosome 4q25 was linked to exceptional human longevity, and a haplotype of the positional candidate microsomal transfer protein (MTP) gene was associated to the phenotype in U.S. Caucasians. We investigated whether linkage to 4q25 could be detected in 164 nonagenarian sibships of the Leiden Longevity Study. Additionally, we compared the MTP -493G/T and Q95H allele and haplotype frequencies in the Leiden Longevity Study (379 nonagenarians, 525 of their offspring, and 251 partners of their offspring) and in the Leiden 85-Plus Study (655 octogenarians and 244 young controls).

Starting from young to very old subjects, aging is associated with a progressive remodeling. Such an age-dependent remodeling process mainly affects anthropometrics, endocrine and thus, also metabolic factors. Interestingly, it occurs in some individuals successfully, while in others unsuccessfully. Centenarians in good health conditions are a very selected group of subjects representing an exceptional condition. Why the centenarians reach the extreme human life span is still unknown.

The exceptional longevity of centenarians is due in part to inherited genetic factors, as deduced from data that show that first degree relatives of centenarians live longer and have reduced overall mortality. In recent years, a number of groups have performed genetic association studies on long-living individuals (LLI) and young controls to identify alleles that are either positively or negatively selected in the centenarian population as consequence of a demographic pressure. Many of the reported studies have shown genetic loci associated with longevity.

The human forkhead box O3A gene (FOXO3A) encodes an evolutionarily conserved key regulator of the insulin-IGF1 signaling pathway that is known to influence metabolism and lifespan in model organisms. A recent study described 3 SNPs in the FOXO3A gene that were statistically significantly associated with longevity in a discovery sample of long-lived men of Japanese ancestry [Willcox et al. (2008) Proc Natl Acad Sci USA 105:13987-13992]. However, this finding required replication in an independent population.

Frontier populations provide exceptional opportunities to test the hypothesis of a trade-off between fertility and longevity. In such populations, mechanisms favoring reproduction usually find fertile ground, and if these mechanisms reduce longevity, demographers should observe higher postreproductive mortality among highly fertile women.

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.

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.

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).