Morbidity of Tokyo-Area Centenarians and Its Relationship to Functional Status

This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. The ApoE gene is associated with the risk of Alzheimer or cardiovascular disease but its influence on exceptional longevity (EL) is uncertain. Our primary purpose was to determine, using a case-control design, if the ApoE gene is associated with EL. We compared ApoE allele/genotype frequencies among the following cohorts: cases (centenarians, most with 1 + major disease condition; n = 163, 100-111 years) and healthy controls (n = 1039, 20-85 years) from Spain; disease-free cases (centenarians; n = 79, 100-104 years) and healthy controls (n = 597, age 27-81 years) from Italy; and cases (centenarians and semi-supercentenarians, most with 1+ major disease condition; n = 729, 100-116 years) and healthy controls (n = 498, 23-59 years) from Japan. Our main findings were twofold. First, the ε4-allele was negatively associated with EL in the three cohorts, with the following odds ratio (OR) values (adjusted by sex) having been found: 0.55 (95% confidence interval (CI): 0.33, 0.94), P = 0.030 (Spain); 0.41 (95%CI: 0.18, 0.99), P = 0.05 (Italy); and 0.35 (95%CI: 0.26, 0.57), P b 0.001 (Japan). Second, although no association was found in the Spanish cohort (OR = 1.42 (95%CI: 0.89, 2.26), P = 0.145), the ε2-allele was positively associated with EL in the Italian (OR = 2.14 (95%CI: 1.18, 3.45), P = 0.01) and Japanese subjects (OR = 1.81 (95%CI: 1.25, 2.63), P = 0.002). Notwithstanding the limitations of case-control designs, our data suggest that the ApoE might be a candidate to influence EL. The ε4-allele appears to decrease the likelihood of reaching EL among individuals of different ethnic/geographic origins. An additional, novel finding of our study was that the ε2-allele might favor EL, at least in the Italian and Japanese cohorts.

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Section: Japanese Cohortmentioning

confidence: 99%

ApoE gene and exceptional longevity: Insights from three independent cohorts

Garatachea

Emanuele

Calero

et al. 2014

Experimental Gerontology

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“…Consequently, a total of 450 centenarians (58 men, 392 women) were enrolled in the SSC-J by the end of November 2011. The phenotype and disease characteristics of the Japanese centenarians are described elsewhere (Takayama et al 2007), with a prevalence of hypertension, CVD, and dementia of 63.6, 28.8, and 59.4 %, respectively. Inclusion criteria for the control group, which was recruited during years 2008-2012 by advertising, were being man or woman aged <60 years, and free of diagnosed stroke, cardiac disease, and chronic renal failure (as reported in a questionnaire).…”

Section: Japanese Cohortmentioning

confidence: 99%

FNDC5 (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs

Sanchís-Gomar

Garatachea

et al. 2014

AGE

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Irisin might play an important role in reducing the risk of obesity, insulin resistance, or several related diseases, and high irisin levels may contribute to successful aging. Thus, the irisin precursor (FNDC5) gene is a candidate to influence exceptional longevity (EL), i.e., being a centenarian. It has been recently shown that two single-nucleotide polymorphisms (SNPs) in the FNDC5 gene, rs16835198 and rs726344, are associated with in vivo insulin sensitivity in adults. We determined luciferase gene reporter AGE (2014) 36:9733 DOI 10.1007 Fabian Sanchis-Gomar and Nuria Garatachea contributed equally to this paper activity in the two above-mentioned SNPs and studied genotype distributions among centenarians (n=175, 144 women) and healthy controls (n=347, 142 women) from Spain. We also studied an Italian [79 healthy centenarians (40 women) and 316 healthy controls (156 women)] and a Japanese cohort [742 centenarians (623 women) and 499 healthy controls (356 women)]. The rs726344 SNP had functional significance, as shown by differences in luciferase activity between the constructs of this SNP (all P≤0.05), with the variant A-allele having higher luciferase activity compared with the G-allele (P = 0.04). For the rs16835198 SNP, the variant T-allele tended to show higher luciferase activity compared with the G-allele (P=0.07). However, we found no differences between genotype/allele frequencies of the two SNPs in centenarians versus controls in any cohort, and no significant association (using logistic regression adjusted by sex) between the two SNPs and EL. Further research is needed with different cohorts as well as with additional variants in the FNDC5 gene or in other genes involved in irisin signaling.

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“…Paolisso et al were the first to report that glucose tolerance and insulin sensitivity are better preserved in healthy centenarians in comparison to elderly individuals over 75 years of age 33) . A series of crosssectional studies have reproducibly demonstrated that the prevalence of type 2 diabetes, which is closely associated with age-related insulin resistance, is very low among Finnish 34) , Italian 35) , and Japanese centenarians 36) . In addition, Barzilai et al reported a low prevalence of MS among centenarians and their offspring, which was associated with a larger particle size of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) 37) .…”

Section: Human Data On the Adipose Tissue Phenotype In Centenariansmentioning

confidence: 99%

Adipokines and Aging

Arai

Takayama

Abe

et al. 2011

JAT

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Dysregulation of adipose tissue-derived bioactive molecules, termed adipokines, is recognized as common ground for insulin resistance and metabolic syndrome associated with obesity. However, adipokine dysregulation is paradoxically associated with lipodystrophy and lipoatrophy with aging. In familial partial lipodystrophic syndromes and Hutchinson-Gilford progeria syndrome, both of which are caused by mutations in the LMNA gene, loss of adipose tissue is associated with adipokine dysregulation, insulin resistance, and atherosclerosis, suggesting a critical role of adipose tissue function in controlling whole body energy metabolism, age-related pathologies, and longevity. Centenarians, a model of healthy aging and longevity, are reported to exhibit preserved insulin sensitivity as well as favorable adipokine profiles, particularly high levels of circulating adiponectin. Furthermore, adipose tissue dysfunction indicated by dysregulation of leptin, tumor necrosis factor-, and adiponectin is associated with poor prognosis in centenarians. In contrast to results obtained for obesity, adipokine dysregulation in centenarians is associated with very low leptin levels, suggesting that age-related lipoatrophy is the major factor for adipose tissue dysfunction at an advanced age. These observations suggest that adipose tissue excess as well as its aging is implicated in the regulation of adipokines, insulin sensitivity, and lifespan in humans.J Atheroscler Thromb, 2011; 18:545-550.

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Morbidity of Tokyo-Area Centenarians and Its Relationship to Functional Status

Cited by 87 publications

References 25 publications

ApoE gene and exceptional longevity: Insights from three independent cohorts

ApoE gene and exceptional longevity: Insights from three independent cohorts

FNDC5 (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs

Adipokines and Aging

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