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The rs2802292, rs2764264 and rs13217795 variants of FOXO3 have been associated with extreme longevity in multiple human populations, but the mechanisms underpinning this remain unclear. We aimed to characterise potential effects of longevity-associated variation on the expression and mRNA processing of the FOXO3 gene. We performed a comprehensive assessment of FOXO3 isoform usage across a wide variety of human tissues and carried out a bioinformatic analysis of the potential for longevity-associated variants to disrupt regulatory regions involved in isoform choice. We then related the expression of full length and 5′ truncated FOXO3 isoforms to rs13217795 genotype in peripheral blood and skeletal muscle from individuals of different rs13217795 genotypes. FOXO3 isoforms displayed considerable tissue specificity. We determined that rs13231195 and its tightly aligned proxy variant rs9400239 may lie in regulatory regions involved in isoform choice. The longevity allele at rs13217795 was associated with increased levels of full length FOXO3 isoforms in peripheral blood and a decrease in truncated FOXO3 isoforms in skeletal muscle RNA. We suggest that the longevity effect of FOXO3 SNPs may in part derive from a shift in isoform usage in skeletal muscle away from the production of 5′ truncated FOXO3 isoforms lacking a complete forkhead DNA binding domain, which may have compromised functionality. [ABSTRACT FROM AUTHOR]

Basho-fu (Musa liukiuensis) weaving has long been part of the cultural identity of Ogimi villagers and has continued in the village as a cottage industry despite its almost complete disappearance throughout the rest of the Ryukyu archipelago. It has survived largely due to the concerted efforts of a few villagers and is now carried on mainly by middle-aged and older women. Almost every elderly woman in Ogimi has at least some experience in basho-fu weaving, and most still participate in some stage of the production process. Aged women form the bulk of the core group of workers that carries out the labor-intensive u-umi (spooling) and u-biki (fiber-cleaning) activities. Without this core group of elderly women, the whole production process would be in jeopardy. Thus, older women in Ogimi play a key role as valued workers in maintaining the basho-fu production process. In exchange for their continued participation, these elderly women receive symbolic capital in the form of respect and honors, as well as wages for their labor. We argue that participating in traditional basho-fu weaving helps these older women maintain an active engagement with life as healthy and productive members of society, a role that has been culturally sanctioned and has taken on moral import in Japan's rapidly aging society. Interestingly, "doing basho" may be considered one means to help achieve successful aging in this particular cultural context. [ABSTRACT FROM AUTHOR]

Centenarians represent a rare phenotype appearing in roughly 10-20 per 100,000 persons in most industrialized countries but as high as 40-50 per 100,000 persons in Okinawa, Japan. Siblings of centenarians in Okinawa have been found to have cumulative survival advantages such that female centenarian siblings have a 2.58-fold likelihood and male siblings a 5.43-fold likelihood (versus their birth cohorts) of reaching the age of 90 years. This is indicative of a strong familial component to longevity. Centenarians may live such extraordinarily long lives in large part due to genetic variations that either affect the rate of aging and/or have genes that result in decreased susceptibility to age-associated diseases. Some of the most promising candidate genes appear to be those involved in regulatory pathways such as insulin signaling, immunoinflammatory response, stress resistance or cardiovascular function. Although gene variants with large beneficial effects have been suggested to exist, only APOE, an important regulator of lipoproteins has been consistently associated with a longer human lifespan across numerous populations. As longevity is a very complex trait, several issues challenge our ability to identify its genetic influences, such as control for environmental confounders across time, the lack of precise phenotypes of aging and longevity, statistical power, study design and availability of appropriate study populations. Genetic studies on the Okinawan population suggest that Okinawans are a genetically distinct group that has several characteristics of a founder population, including less genetic diversity, and clustering of specific gene variants, some of which may be related to longevity. Further work on this population and other genetic isolates would be of significant interest to the genetics of human longevity. [ABSTRACT FROM AUTHOR]

Caloric (or dietary) restriction (CR) extends lifespan and lowers risk for age associated diseases in a phylogenetically diverse group of species. Whether prolonged CR increases average or maximum lifespan or promotes a more youthful physiology in humans at advanced ages is not yet known. However, available epidemiological evidence indicates that CR may already have contributed to an extension of average and maximum life span in one human population and appears to have lowered risk for age associated chronic diseases in other human populations. We review the human studies in the context of a special human population, older Okinawans, who appear to have undergone a mild form of prolonged CR for about half their adult lives. [ABSTRACT FROM AUTHOR]