Telomere attrition in beta and alpha cells with age - PubMed (original) (raw)

doi: 10.1007/s11357-016-9923-0. Epub 2016 May 24.

Naotaka Izumiyama-Shimomura 2, Yoshiyuki Kimbara 3, Ken-Ichi Nakamura 2, Naoshi Ishikawa 4 5, Junko Aida 2 6, Yuko Chiba 3, Yoko Matsuda 6, Seijiro Mori 3, Tomio Arai 6, Mutsunori Fujiwara 7, Steven S S Poon 2 6, Tatsuro Ishizaki 8, Atsushi Araki 3, Kaiyo Takubo 2 6, Hideki Ito 3

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Telomere attrition in beta and alpha cells with age

Yoshiaki Tamura et al. Age (Dordr). 2016 Jun.

Abstract

We have reported telomere attrition in β and α cells of the pancreas in elderly patients with type 2 diabetes, but it has not been explored how the telomere lengths of these islet cells change according to age in normal subjects. To examine the telomere lengths of β and α cells in individuals without diabetes across a wide range of ages, we conducted measurement of the telomere lengths of human pancreatic β and α cells obtained from 104 autopsied subjects without diabetes ranging in age from 0 to 100 years. As an index of telomere lengths, the normalized telomere-centromere ratio (NTCR) was determined for β (NTCRβ) and α (NTCRα) cells by quantitative fluorescence in situ hybridization (Q-FISH). We found NTCRβ and NTCRα showed almost the same levels and both decreased according to age (p < 0.001 for both). NTCRs decreased more rapidly with age and were more widely distributed (p = 0.036 for NTCRβ, p < 0.001 for NTCRα) in subjects under 18 years of age than in subjects over 18 years. There was a positive correlation between NTCRβ and NTCRα only among adult subjects (p < 0.001). In conclusion, the telomeres of β and α cells become shortened with normal aging process.

Keywords: Aging; Alpha cell; Beta cell; Quantitative fluorescence in situ hybridization (Q-FISH); Telomere.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Fig. 1

Fig. 1

Representative FISH images showing immunofluorescence for insulin (a, b) and glucagon (c, d) in specimens from young (a, c) and old (b, d) subjects. Original magnification, ×40. In all slides, nuclear red, green, and blue signals are those for telomere-Cy3, centromere-FITC, and DAPI counterstaining for DNA, respectively. a, b Cytoplasmic green indicates the insulin-Cy-5 signal. a Image of a specimen from a 4-month-old infant. The NTCR for insulin-positive cells was 3.28. The reddish ivory color is not the telomere signal but non-specific fluorescence from the cytoplasm of islet cells. Red telomere and green centromere signals are always observed within the nuclei. b Images of a specimen from a 72-year-old woman. The NTCR for insulin-positive cells was 0.89. c, d Cytoplasmic pink indicates the glucagon-Cy-5 signal. c Image of a specimen from a 0-day-old neonate. The NTCR for glucagon-positive cells was 2.85 in this sample. d Image of a specimen from an 84-year-old woman. The NTCR for glucagon-positive cells was 0.88 in this sample

Fig. 2

Fig. 2

Telomere length dynamics in pancreatic α and β cells relevant to age. scatter plot analyses of the whole sample by a simple regression model, statistically significant regression lines are shown in red with decreasing slopes (p < 0.001, Solid line for NTCRβ: y = −0.0081_x_ + 1.81, and dotted line for NTCRα: y = −0.011_x_ + 1.86). In piecewise linear regression fits with a breakpoint at 18 years of age , regression lines are shown in black for each cell type (solid line for NTCRβ −0.0408_X_ + 2.029 (0–18 years), −0.0017_X_ + 1.326 (18–100 years), and dotted line for NTCRα −0.0506_X_ + 2.126 (0–18 years), −0.0032_X_ + 1.273 (18–100 years)). The regression models of NTCR to age for both β and α cells were significant (p < 0.001). The data distributions for NTCRα and NTCRβ were not significantly different from one another (p = 0.229)

Fig. 3

Fig. 3

Correlation between NTCRβ and NTCRα. (p < 0.001). a Plots for the subjects as a whole. NTCRβ and NTCRα were positively correlated with each other (p < 0.001). b Plots for the subjects divided into two age categories, under 18 and 18 years and over. A significant positive correlation was found only for the adult group (p = 0.01)

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