ABSTRACT
Introducción. La longevidad viene determinada por la genética propia de cada especie y por factores externos, tales como nutricionales, ambientales, sociales, etc. Sin embargo, los individuos más longevos se caracterizan por presentar una mayor adaptación al entorno condicionada predominantemente por su propia genética. Dentro de una misma población con relativa homogeneidad genotípica, podemos encontrar cambios sutiles en la secuencia de ADN que afectan únicamente a un nucleótido. Estos cambios denominados polimorfismos de nucleótido simple (Single Nucleotide Polimorphisim [SNP]) se encuentran con una prevalencia mayor al 1-5% de la población. Por ello, nos planteamos estudiar en individuos centenarios si las posibles variaciones genéticas, analizando SNP, podrían tener alguna relevancia en la longevidad extrema que experimentan. Material y métodos. Se reclutó a 92 sujetos: 28 centenarios y 64 controles. Se les extrajo sangre, se aisló y amplificó ADN para el análisis de SNP mediante la tecnología Axiom Genotyping de Affymetrix. Los análisis estadísticos se realizaron mediante el programa Plink y varias bibliotecas de R para Windows (library SNPassoc, skatMeta). Resultados. Los resultados del análisis muestran 12 SNP que presentan un valor de p inferior a 0,001, donde 5 de ellos (DACH1, LOC91948, BTB16, NFIL3 y HDAC4) tienen funciones reguladoras de la expresión de otros genes. Conclusiones. Así pues, los resultados sugieren que las variaciones genéticas observadas entre centenarios y controles tienen lugar en 5 genes que están implicados en la regulación de la expresión génica, capacitándolos a adaptarse a diferentes condiciones ambientales con mejor éxito (AU)
Introduction. Longevity is determined by genetic and external factors, such as nutritional, environmental, social, etc. Nevertheless, when living conditions are optimal, longevity is determined by genetic variations between individuals. In a same population, with relative genotypic homogeneity, subtle changes in the DNA sequence affecting a single nucleotide can be observed. These changes, called single nucleotide polymorphisms (SNP) are present in 1-5% of the population. Material and methods. A total of 92 subjects were recruited, including 28 centenarians and 64 controls, in order to find SNP that maybe implicated in the extreme longevity, as in the centenarians. Blood samples were collected to isolate and amplify the DNA in order to perform the analysis of SPN by Axiom Genotyping of Affymetrix technology. Statistical analyses were performed using the Plink program and libraries SNPassoc and skatMeta. Results. Our results show 12 mutations with a p<.001, where 5 of these (DACH1, LOC91948, BTB16, NFIL3 y HDAC4) have regulatory functions of the expressions of others genes. Conclusions. Therefore, these results suggest that the genetic variation between centenarians and controls occurs in five genes that are involved in the regulation of gene expression to adapt to environmental changes better than controls (AU)
Subject(s)
Humans , Male , Female , Middle Aged , Amplified Fragment Length Polymorphism Analysis/methods , Amplified Fragment Length Polymorphism Analysis , Gene Expression/physiology , Longevity/physiology , Blood Chemical Analysis/methods , Genotyping Techniques/methods , 28599 , Aging/pathology , Bioethics/trends , Case-Control Studies , Helsinki Declaration , Informed Consent/standardsABSTRACT
INTRODUCTION: Human longevity is a complex issue influenced by genetic and environmental factors. Oxidative stress (OE) could play an important role in this process. Succesful aging could be related with the organism ability facing OE. In the present study we compared malondialdehyde (MDA) and oxidized proteins (OP) plasma levels, in elderly people older than 97 years and 70-80 years old, to better understand the effects of OE on human longevity. MATERIAL AND METHODS: Population-based case control study. We considered as cases patients who were born and live on la Ribera county in Valencia (Spain) older than 97 years old and who accepted to participate in the study. Controls were from the same poblational base, chosen randomly, and 70-80 years old. We made a descriptive analysis of sociodemographic, clinic and functional variables; an odds ratio (OR) estimation of being centenarian by OP and MDA quartiles; and a tendency analysis by Mantel-Haenszel test. RESULTS: Twenty eight cases and 31 controls were included. Functional state and robust percentage were worse in cases. MDA (1,44±0,45 vs 1,84±0,59, p=0,005), and OP (64,29±15,73 vs. 76,52±13,44, p=0,002) levels, were significantly lower in cases. The OR of being centenarian in lower/higher quartile were 3,8 for MDA and 5,7 for OP, with a Mantel-Haenszel signification of 0,029 and 0,044 respectively. CONCLUSIONS: In our study OE level were lower in centenarians than in younger elderly, and the lower the OE grade, the higher were the likelihood of being centenarian.
