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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.

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Related in: MedlinePlus

Representative histological features of the skin from patients with Werner syndrome (WS)Representative images of skin specimens from WS patients, stained with hematoxylin and eosin. The left panel (A) shows a sample of skin after removal of dermal tissue with a scalpel, and the right panel (B) shows a sample before such treatment. Dashed line indicates the treatment border. Figures A and B show microscopic views of skin from the ankle of a 43-year-old man (WS-2) and the lower leg of a 41-year-old man (WS-7), respectively. Remarkable atrophy of the epidermis and dermis is evident. Mild hyperkeratosis, mild dermal hyalinization, and atrophy of the skin appendages (hair follicles) are present in both cases, with marked flattening of the rete ridges in (A). No marked inflammatory cell infiltration is evident in either case. Scale bar, 50 μm.
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Figure 1: Representative histological features of the skin from patients with Werner syndrome (WS)Representative images of skin specimens from WS patients, stained with hematoxylin and eosin. The left panel (A) shows a sample of skin after removal of dermal tissue with a scalpel, and the right panel (B) shows a sample before such treatment. Dashed line indicates the treatment border. Figures A and B show microscopic views of skin from the ankle of a 43-year-old man (WS-2) and the lower leg of a 41-year-old man (WS-7), respectively. Remarkable atrophy of the epidermis and dermis is evident. Mild hyperkeratosis, mild dermal hyalinization, and atrophy of the skin appendages (hair follicles) are present in both cases, with marked flattening of the rete ridges in (A). No marked inflammatory cell infiltration is evident in either case. Scale bar, 50 μm.

Mentions: To define the histopathological characteristics of the skin samples, we performed microscopy analyses. Figures 1A and B show representative microscopic views of the skin tissues from WS patients. The sample on the left (A) is a piece of skin tissue from which dermal tissue had been removed with a scalpel, and the sample on the right (B) is one that was not subjected to such treatment. To determine the representative cell species in each tissue, we counted the numbers of nuclei. The numbers of keratinocytes and non-keratinocytes (including dermal fibroblasts, capillary endothelial cells, and lymphocytes) in section A were 3.3 × 102 (182) and 1.2 × 102 (112), respectively, and those in section B were 5.7 × 102 (242) and 2.2 × 102 (152), respectively. Hence, the ratio of keratinocytes to non-keratinocytes in the samples from which genomic DNA was extracted was 183: 113 in (A) and 243: 153 in (B), thus being approximately 4:1 in both cases. Similar values were obtained in the other cases of WS. Consequently, keratinocytes were considered to be a suitable representative cell type for each skin sample. With regard to muscle tissues, myocytes were the representative cell type.


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)

Representative histological features of the skin from patients with Werner syndrome (WS)Representative images of skin specimens from WS patients, stained with hematoxylin and eosin. The left panel (A) shows a sample of skin after removal of dermal tissue with a scalpel, and the right panel (B) shows a sample before such treatment. Dashed line indicates the treatment border. Figures A and B show microscopic views of skin from the ankle of a 43-year-old man (WS-2) and the lower leg of a 41-year-old man (WS-7), respectively. Remarkable atrophy of the epidermis and dermis is evident. Mild hyperkeratosis, mild dermal hyalinization, and atrophy of the skin appendages (hair follicles) are present in both cases, with marked flattening of the rete ridges in (A). No marked inflammatory cell infiltration is evident in either case. Scale bar, 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Representative histological features of the skin from patients with Werner syndrome (WS)Representative images of skin specimens from WS patients, stained with hematoxylin and eosin. The left panel (A) shows a sample of skin after removal of dermal tissue with a scalpel, and the right panel (B) shows a sample before such treatment. Dashed line indicates the treatment border. Figures A and B show microscopic views of skin from the ankle of a 43-year-old man (WS-2) and the lower leg of a 41-year-old man (WS-7), respectively. Remarkable atrophy of the epidermis and dermis is evident. Mild hyperkeratosis, mild dermal hyalinization, and atrophy of the skin appendages (hair follicles) are present in both cases, with marked flattening of the rete ridges in (A). No marked inflammatory cell infiltration is evident in either case. Scale bar, 50 μm.
Mentions: To define the histopathological characteristics of the skin samples, we performed microscopy analyses. Figures 1A and B show representative microscopic views of the skin tissues from WS patients. The sample on the left (A) is a piece of skin tissue from which dermal tissue had been removed with a scalpel, and the sample on the right (B) is one that was not subjected to such treatment. To determine the representative cell species in each tissue, we counted the numbers of nuclei. The numbers of keratinocytes and non-keratinocytes (including dermal fibroblasts, capillary endothelial cells, and lymphocytes) in section A were 3.3 × 102 (182) and 1.2 × 102 (112), respectively, and those in section B were 5.7 × 102 (242) and 2.2 × 102 (152), respectively. Hence, the ratio of keratinocytes to non-keratinocytes in the samples from which genomic DNA was extracted was 183: 113 in (A) and 243: 153 in (B), thus being approximately 4:1 in both cases. Similar values were obtained in the other cases of WS. Consequently, keratinocytes were considered to be a suitable representative cell type for each skin sample. With regard to muscle tissues, myocytes were the representative cell type.

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