Limits...
Accelerated in vivo epidermal telomere loss in Werner syndrome.

Ishikawa N, Nakamura K, Izumiyama-Shimomura N, Aida J, Ishii A, Goto M, Ishikawa Y, Asaka R, Matsuura M, Hatamochi A, Kuroiwa M, Takubo K - Aging (Albany NY) (2011)

Bottom Line: Regression analyses indicated that the TRF length in WS was significantly shorter than that in controls (p < 0.001).Furthermore, we found that TRF lengths in muscle adjacent to the examined epidermis were also significantly shorter than those of controls (p = 0.047).These data demonstrate for the first time that in vivo telomere loss is accelerated in systemic organs of WS patients, suggesting that abnormal telomere erosion is one of the major causes of early onset of age‐related symptoms and a predisposition to sarcoma and carcinoma in WS.

View Article: PubMed Central - PubMed

Affiliation: Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173‐0015, Japan. naoshi@tmig.or.jp

ABSTRACT
Many data pertaining to the accelerated telomere loss in cultured cells derived from Werner syndrome (WS), a representative premature aging syndrome, have been accumulated. However, there have been no definitive data on in vivo telomere shortening in WS patients. In the present study, we measured terminal restriction fragment (TRF) lengths of 10 skin samples collected from extremities of 8 WS patients aged between 30 and 61 years that had been surgically amputated because of skin ulceration, and estimated the annual telomere loss. Whereas the values of TRF length in younger WS patients (in their thirties) were within the normal range, those in older WS patients were markedly shorter relative to non‐WS controls. Regression analyses indicated that the TRF length in WS was significantly shorter than that in controls (p < 0.001). Furthermore, we found that TRF lengths in muscle adjacent to the examined epidermis were also significantly shorter than those of controls (p = 0.047). These data demonstrate for the first time that in vivo telomere loss is accelerated in systemic organs of WS patients, suggesting that abnormal telomere erosion is one of the major causes of early onset of age‐related symptoms and a predisposition to sarcoma and carcinoma in WS.

Show MeSH

Related in: MedlinePlus

Scatter plot analysis of HinfI-digested TRF length in skin samples from WS patients and controlsMultiple regression analysis yielded a regression line for the 8 WS patients (10 samples) (Y = 20.7 − 0.139X (age) − 3.6 (WS group: 1); in red), and a regression line for the non-WS control subjects, aged between 30 and 80 years (n = 21) (Y = 20.7 − 0.139X (age) − 3.6 (control group: 0); control line denoted in blue). The difference of TRF values between the groups was significant. P = 0.00026. The same patient at the ages of 37 and 43 years (WS-4 case: ◆). The same patient at the ages of 41 and 44 years (WS-7 case: ■).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3117457&req=5

Figure 3: Scatter plot analysis of HinfI-digested TRF length in skin samples from WS patients and controlsMultiple regression analysis yielded a regression line for the 8 WS patients (10 samples) (Y = 20.7 − 0.139X (age) − 3.6 (WS group: 1); in red), and a regression line for the non-WS control subjects, aged between 30 and 80 years (n = 21) (Y = 20.7 − 0.139X (age) − 3.6 (control group: 0); control line denoted in blue). The difference of TRF values between the groups was significant. P = 0.00026. The same patient at the ages of 37 and 43 years (WS-4 case: ◆). The same patient at the ages of 41 and 44 years (WS-7 case: ■).

Mentions: The median values of the HinfI-digested TRF lengths for 10 WS subjects were plotted as a function of age (Figure 3, Supplementary data Figure S2A). The median values of the HinfI-digested TRF lengths for skin in the 56 non-WS control subjects were also plotted as a function of age (Supplementary data, Figure S2A).


Accelerated in vivo epidermal telomere loss in Werner syndrome.

Ishikawa N, Nakamura K, Izumiyama-Shimomura N, Aida J, Ishii A, Goto M, Ishikawa Y, Asaka R, Matsuura M, Hatamochi A, Kuroiwa M, Takubo K - Aging (Albany NY) (2011)

Scatter plot analysis of HinfI-digested TRF length in skin samples from WS patients and controlsMultiple regression analysis yielded a regression line for the 8 WS patients (10 samples) (Y = 20.7 − 0.139X (age) − 3.6 (WS group: 1); in red), and a regression line for the non-WS control subjects, aged between 30 and 80 years (n = 21) (Y = 20.7 − 0.139X (age) − 3.6 (control group: 0); control line denoted in blue). The difference of TRF values between the groups was significant. P = 0.00026. The same patient at the ages of 37 and 43 years (WS-4 case: ◆). The same patient at the ages of 41 and 44 years (WS-7 case: ■).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117457&req=5

Figure 3: Scatter plot analysis of HinfI-digested TRF length in skin samples from WS patients and controlsMultiple regression analysis yielded a regression line for the 8 WS patients (10 samples) (Y = 20.7 − 0.139X (age) − 3.6 (WS group: 1); in red), and a regression line for the non-WS control subjects, aged between 30 and 80 years (n = 21) (Y = 20.7 − 0.139X (age) − 3.6 (control group: 0); control line denoted in blue). The difference of TRF values between the groups was significant. P = 0.00026. The same patient at the ages of 37 and 43 years (WS-4 case: ◆). The same patient at the ages of 41 and 44 years (WS-7 case: ■).
Mentions: The median values of the HinfI-digested TRF lengths for 10 WS subjects were plotted as a function of age (Figure 3, Supplementary data Figure S2A). The median values of the HinfI-digested TRF lengths for skin in the 56 non-WS control subjects were also plotted as a function of age (Supplementary data, Figure S2A).

Bottom Line: Regression analyses indicated that the TRF length in WS was significantly shorter than that in controls (p < 0.001).Furthermore, we found that TRF lengths in muscle adjacent to the examined epidermis were also significantly shorter than those of controls (p = 0.047).These data demonstrate for the first time that in vivo telomere loss is accelerated in systemic organs of WS patients, suggesting that abnormal telomere erosion is one of the major causes of early onset of age‐related symptoms and a predisposition to sarcoma and carcinoma in WS.

View Article: PubMed Central - PubMed

Affiliation: Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173‐0015, Japan. naoshi@tmig.or.jp

ABSTRACT
Many data pertaining to the accelerated telomere loss in cultured cells derived from Werner syndrome (WS), a representative premature aging syndrome, have been accumulated. However, there have been no definitive data on in vivo telomere shortening in WS patients. In the present study, we measured terminal restriction fragment (TRF) lengths of 10 skin samples collected from extremities of 8 WS patients aged between 30 and 61 years that had been surgically amputated because of skin ulceration, and estimated the annual telomere loss. Whereas the values of TRF length in younger WS patients (in their thirties) were within the normal range, those in older WS patients were markedly shorter relative to non‐WS controls. Regression analyses indicated that the TRF length in WS was significantly shorter than that in controls (p < 0.001). Furthermore, we found that TRF lengths in muscle adjacent to the examined epidermis were also significantly shorter than those of controls (p = 0.047). These data demonstrate for the first time that in vivo telomere loss is accelerated in systemic organs of WS patients, suggesting that abnormal telomere erosion is one of the major causes of early onset of age‐related symptoms and a predisposition to sarcoma and carcinoma in WS.

Show MeSH
Related in: MedlinePlus