RESUMEN
Many studies have demonstrated the association between telomere length in mitotic cells and carcinogenesis and mortality, but little attention has been focused on post-mitotic cells and human life expectancy. We assessed the relationship between telomere length in cerebral gray and white matter and longevity in 72 autopsied Japanese patients aged 0-100 years using Southern blot hybridization. The mean telomere lengths in the gray and white matter were 12.3+/-2.5 kilobase pairs and 11.4+/-2.1 kilobase pairs, respectively. The mean telomere lengths in 60-69 year decadal group were less than those of neonates, and declined further in the 70-79-year age group, but those in groups of further advanced age were longer than in the 70-79 year group (70-79<80-89<90-100 years of age). Thus, the 90-100-year age group possessed significantly longer telomeres than the 70s (p=0.029). Autopsy protocols showed a decrease in the rate of cancer death in individuals in their 80s (p=0.041) and 90s (p=0.017) versus those in their 60s, and in their 80s the mean telomere length in the gray matter from cancer death patients was significantly shorter than that of patients who died of other diseases (p=0.04). These data suggest that innate telomere lengths are maintained very well in the cerebrum, and are associated with longevity. Our study lends indispensable support to the hypothesis that longer telomeres protect the genome from instability (a major cause of carcinogenesis) and are beneficial for longevity.
Asunto(s)
Longevidad/genética , Lóbulo Occipital/ultraestructura , Telómero/ultraestructura , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/genética , Southern Blotting , Transformación Celular Neoplásica/genética , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Persona de Mediana EdadRESUMEN
We have conducted systematic studies to measure telomere length in human tissues of all types. Progressive telomere shortening with aging was studied in specimens of normal pancreas obtained at autopsy from 69 subjects aged 0 to 100 yr, and age-related shortening of telomere length at a rate of 36 base pairs (bp) per year was detected. Mean telomere length (+/-SD) was 13.9+/-1.4 kilobase pairs (kbp) in 16 neonates, as opposed to 8.4 kbp in 2 centenarians. Mean telomere length (+/-SD) in four age groups, 0-24, 25-49, 50-74, and 75-100 yr, was 13.5+/-1.5, 12.3+/-0.7, 11.3+/-2.5, and 10.7+/-1.8, respectively.
Asunto(s)
Envejecimiento/genética , Páncreas/fisiología , Telómero/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , ADN/análisis , Femenino , Humanos , Lactante , Longevidad/genética , Masculino , Persona de Mediana Edad , Páncreas/química , Páncreas/citologíaRESUMEN
We investigated progressive telomere shortening in normal human epidermis and lingual epithelium during aging, and attempted, in particular, to ascertain whether the telomere shortening that accompanies aging occurs at the same rate in different tissues. We studied telomeric DNA integrity, and estimated annual telomere loss, in 52 specimens of epidermis and 48 specimens of lingual epithelium collected at autopsy from subjects who had died at ages between 0 and 101 y. Most of the DNA samples were measured twice by southern blot hybridization. In addition, the correlation between telomere lengths in the two types of tissues was examined. The telomere reduction rates in epidermis and lingual epithelium were 36 bp and 30 bp per y, respectively, and these were significantly different. The rates obtained by the second measurements in epidermis and lingual epithelium were 39 and 32 bp per y, respectively, and these were also significantly different. The mean telomere lengths in the epidermis of eight neonates and the lingual epithelium of seven neonates were 13.2+/-1.0 and 13.8+/-1.0 kb, respectively. Comparison of telomere lengths in the two tissues for 41 paired samples showed that the mean telomere length in the epidermis (10.7+/-2.3 kb) was less than that in the lingual epithelium (12.4+/-2.5 kb); however, statistical analysis revealed a very significant relationship between epidermal and lingual epithelial telomere length (r=0.842, p<0.0001). These results indicate that the telomeres in epidermis and lingual epithelium are characterized by tissue-specific loss rates.
Asunto(s)
Epidermis/patología , Envejecimiento de la Piel/patología , Telómero/patología , Lengua/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Southern Blotting , Niño , Preescolar , Epitelio/patología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Análisis de Regresión , Telómero/genéticaRESUMEN
BACKGROUND: A great deal of attention has been focused on telomeres in relation to cellular aging, immortality, and cancer. However, there is no simple link between telomeres and tissue turnover. We recently proposed a hypothesis that telomere shortening with aging and telomere lengths in different organs are characteristic for human individuals. METHODS: To test this, telomere lengths were measured using DNA from cerebral cortex, myocardium, liver, renal cortex and spleen tissues obtained from human subjects ranging in age from neonates to centenarians. RESULTS: Regression analyses demonstrated telomere reduction rates of 29-60 base pair (bp) per year in the liver, renal cortex and spleen, but no such decrease in the cerebral cortex and myocardium. Significant correlation was found between tissues within individuals, such as cerebral cortex versus (vs) myocardium, cerebral cortex vs liver, cerebral cortex vs renal cortex, myocardium vs liver, myocardium vs renal cortex, and liver vs renal cortex. In most cases, the longest telomeres were observed in the myocardium and the shortest in the liver or renal cortex. CONCLUSIONS: Telomere lengths did not show clear correlation with tissue renewal times in vivo, but rather were characteristic for individuals.