A genetic variant of ACE increases cell survival: a new paradigm for biology and disease

Atzmon

et al. 2005

Circulation Research

269

208

Section: Discussionmentioning

confidence: 99%

Association Between a Functional Variant of the KLOTHO Gene and High-Density Lipoprotein Cholesterol, Blood Pressure, Stroke, and Longevity

Atzmon

et al. 2005

Circulation Research

269

208

International Journal of Cardiology

“…The ACE DD genotype is associated with higher plasma levels of the enzyme, the II genotype with lower ACE levels, and the ID genotype with intermediate levels [5]. Data from experimental studies reported both a functional role for the ACE I/D polymorphism in modulating angiotensin II levels [6], and an increased mRNA expression in white blood cells from subjects carrying the ACE D allele in comparison to subjects carrying the I allele [7].…”

Section: Introductionmentioning

confidence: 96%

Lone and secondary nonvalvular atrial fibrillation: Role of a genetic susceptibility

Fatini

Sticchi

Gensini

et al. 2007

This study highlights the role of ACE gene in predisposing to both lone and secondary NVAF, further contributing to penetrate the genetic mechanisms responsible for this complex disease. The clinical relevance of our results may be related to the possible characterization of subjects predisposed to NVAF in the absence of traditional risk factors, and to the use of ACE-inhibitors therapy able to improve the arrhythmogenic substrate.

“…Studies using samples from these individuals have proved very valuable to identify a variety of factors that influence positively the rate of aging and survival. For instance, it has been demonstrated that several immune parameters are well conserved in healthy centenarians (reviewed in Franceschi et al 1995), at least one gene allele has been identified and linked with their increased longevity (reviewed in Petropoulou et al 2000) and several additional polymorphisms, including variants of the insulinlike growth factor I receptor, the phosphoinositide 3-kinase and ACE (Bonafe et al 2003;Hamdi and Castellon 2004), have been found to participate actively in contributing to the adaptive response during very old age, thus to longevity. Following these findings, one of us has proposed that centenarians are equipped with either more efficient protective molecules (or biochemical pathways to activate such molecules) or, alternatively, with the same protective molecules as found in normal individuals but having a prolonged duration of function (Gonos 2000).…”

Section: Introductionmentioning

confidence: 98%

Cloning of differentially expressed genes in skin fibroblasts from centenarians

et al. 2004

Normal human fibroblasts undergoing serial passaging have been extensively used to identify genes linked with aging. Most of the isolated genes relate to growth retardation signals and the failure of homeostasis that accompanies aging and senescence. In contrast, there is still limited knowledge regarding the nature of the genes that influence positively the rate of aging and longevity. Healthy centenarians represent the best example of successful aging and longevity. Studies using samples from these individuals have proved very valuable for identifying a variety of factors that contribute to successful aging. The aim of the current work was to take advantage of skin fibroblast cultures established from healthy donors including centenarians in order to clone differentially expressed genes in centenarians. First, we demonstrate that centenarian derived cultures follow the typical Hayflick curve and they enter senescence after serial passaging. Application of differential screening techniques in minimally passaged cultures of four control donors of different ages (18-80 years old) and four centenarians has resulted in the cloning of six differentially expressed genes in centenarians. Four of the cloned genes, namely adlican, KBL, EST 38 and EST 39, were over-expressed in centenarians, while VDUP1 and OCIF were down-regulated in the same samples. We have also compared the expression levels of two representative cloned genes in cultures of human embryonic and adult fibroblasts to establish potential links with replicative senescence. Interestingly, VDUP1 was found over-expressed in late passage cells, while EST 39 was down-regulated in the same cultures. Thus our work demonstrates that a combination of the use of both biopsies derived cells and classical in vitro cells passaging will facilitate the better understanding of the biology of aging and longevity.