Telomere shortening with aging in human esophageal mucosa

Abstract

Progressive telomere shortening with aging was studied using normal esophageal mucosal specimens from 177 human subjects aged between 0 and 102 years (yrs). We observed age-related shortening of the telomere, at a rate of 60 base pairS (bp) per year (yr). The mean telomere length of 12 neonates was 15.2 kilobase pairs (kbp) and that of 2 centenarians was 9.3 kbp. Mean (+ SD) telomere lengths were 14.9+1.3, 14.0-~_1.8, 10.1+3.7, 10.4+3.3 and 9.5+3.1 kbp for the age groups less than 2 yrs, 2-20 yrs, 21-60 yrs, 61-80 yrs and 81-102 yrs, respectively. The variation in telomere length among individuals in the same age group was greater for the 3 older groups than for the 2 younger groups, as shown by the SDs. Furthermore, older individuals had greater telomere length variation than younger individuals, based on the lengths of DNA digested smears. Although the telomere length decreased significantly with aging at the rate of 60 bp per yr, differences in the mean telomere lengths between the 3 older age groups were not significant. Rapid shortening occurred in the young generations and there was no further substantial decrease in the esophageal mucosa after 60 yrs of age. Compared to the very rapid renewal rate of the esophageal epithelial cells, the annual reduction rate in telomere length was very low. These findings support the hypothesis that germ cells in the esophageal epithelium have a mechanism to lengthen telomeres.

Telomere shortening in gastric carcinoma with aging despite telomerase activation

“…Terminal restriction fragment lengths, determined by comparing the position of the maximum radioactivity in each lane with the molecular size markers, were regarded as the telomere lengths in these experiments. The clear dierence in smear widths evident for telomeres, indicative of more variation from cell to cell in older individuals, was also found in esophageal mucosae and liver in our previous studies (Takubo et al 1999;Takubo et al 2000).…”

“…In one normal somatic cell division, chromosomes would be expected to lose 50±200 bp of the telomeric sequence (Harley et al 1990;Vaziri et al 1993) and the turnover of gastric epithelia is very rapid, occurring about every 2±6 days (Eastwood 1977), with germ cells demonstrating frequent mitoses. Our data for telomere length in non-neoplastic mucosa, point to a variation across tissues, if one takes into account the ®nding that the telomeres of human esophageal mucosa and liver are 12±15 kbp long at the time of birth (Takubo et al 1999;Takubo et al 2000). Given the fact that the mucous membrane of the stomach is thought to have a renewal time of 5 days or less, 50 or more cell divisions would be required per year for maintenance (Eastwood 1977).…”

“…Human telomere shortening with aging has been reported in peripheral lymphocytes (41 bp/year) (Vaziri et al 1993), epidermal cells (19.8 bp/year) (Lindsey et al 1991), peripheral blood cells (33 bp/year) (Hastie et al 1990), human intestinal mucosa of the large and small intestines (42 bp/year) (Hiyama et al 1996), esophageal mucosa (60 bp/year) (Takubo et al 1999), and liver (55 bp/year) (Takubo et al 2000). The annual telomere loss in gastric mucosa was 46 bp from a mean telomere length for neonatal gastric mucosa of 11.8 kbp.…”

“…We have conducted systemic studies to clarify the reduction rates each year from human tissue of all types and we have found values of 60 bp and 55 bp for esophageal mucosa and liver tissue respectively (Takubo et al 1999;Takubo et al 2000).…”

Determination of Telomere Length by the Quantitative Fluorescence <i>in Situ</i> Hybridization (Q-FISH) Method

“…We have previously determined the annual rates of telomere shortening in a number of different tissues and organs using Southern blotting [2] [3] [14]- [18]. However, unlike cultured cells, tissues are composed of a variety of different cell types, and Southern blotting cannot measure telomere lengths in heterogeneous cell populations, for example in myocardium, which is composed of muscle cells with a few endothelial cells and fibroblasts, hepatic tissue composed of hepatocytes with endothelial cells, fibroblasts and biliary duct cells, and epidermis composed of keratotic cells, granular cells, prickle cells, parabasal cells, and basal cells.…”