Middle Aged

The SIR2/Sirt1 gene has been demonstrated as regulating lifespan in many model organisms, including yeast, Caenorhabditis elegans and rodents. These findings render the human homologue, SIRT1, a very plausible candidate as a modifier of human life expectancy. We therefore sought to investigate whether common allelic variation in the SIRT1 gene was associated with human longevity.

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).

As the elderly population is increasing rapidly, there is a lot of scientific interest in clarifying the differential life-style, genetic, biochemical and molecular factors contributing to mortality or exceptional longevity. Within the framework of the ZINCAGE project, 249 old (60-85 years) and nonagenarian Greek subjects (>/=85 years old) were recruited and anthropometrical, blood and biochemical indices as well as blood pressure measurements were obtained.

We report an illustrative case of bilateral Moore arthroplasty with the clinical and radiographic results at 36 years follow-up. The femoral prostheses were implanted for necrosis of the femoral head when the patient was 46 years old. At implantation the patient's physical activity level was high (Devane 4) and remained so until retirement at age 65 years. His activity level remained high (Devane 3) to the age of 82 years when the patient suffered a Vancouver B1 periprosthetic fracture on the left. At this date, both arthroplasties were free of loosening an osteolysis.

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.

We investigated the hypothesis that gene expression profiles in cultured cell lines from adults, aged 57-97 years, contain information about the biological age and potential longevity of the donors. We studied 104 unrelated grandparents from 31 Utah CEU (Centre d'Etude du Polymorphisme Humain - Utah) families, for whom lymphoblastoid cell lines were established in the 1980s.

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.

Recent studies documented that most centenarians were survivors with multiple comorbidities. We examined morbidities and physical and cognitive function of 302 Japanese centenarians living in Tokyo, and assessed the association between morbidities and functional status. Most centenarians have chronic diseases such as hypertension, heart disease, and stroke. Notably, the prevalence of diabetes mellitus was very low compared with middle-aged Japanese adults. Stroke and fracture were significantly associated with poorer physical and cognitive function.

BACKGROUND: Longevity is a multifactorial trait with a genetic contribution, and mitochondrial DNA (mtDNA) polymorphisms were found to be involved in the phenomenon of longevity. METHODOLOGY/PRINCIPAL FINDINGS: To explore the effects of mtDNA haplogroups on the prevalence of extreme longevity (EL), a population based case-control study was conducted in Rugao--a prefecture city in Jiangsu, China. Case subjects include 463 individuals aged > or = 95 yr (EL group).

CONTEXT: Exceptional longevity is associated with raised serum TSH. OBJECTIVE: The aim of this study was to examine whether offspring of people with exceptional longevity have elevated serum TSH and whether specific single nucleotide polymorphisms (SNPs) in the TSH-B gene and TSH receptor (TSHR) gene are associated with this phenotype. DESIGN/SETTING/PATIENTS: We measured serum TSH and free T(4) in Ashkenazi Jewish centenarians (n = 232; median age, 97 yr), their offspring (n = 366; median age, 69 yr), and age-matched controls without familial longevity (n = 163; median age, 70 yr).