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体外培养的真皮成纤维细胞中的DNA损伤标志物反映了供体的实际年龄。

DNA damage markers in dermal fibroblasts in vitro reflect chronological donor age.

作者信息

Waaijer Mariëtte E C, Croco Eleonora, Westendorp Rudi G J, Slagboom P Eline, Sedivy John M, Lorenzini Antonello, Maier Andrea B

机构信息

Department of Gerontology and Geriatrics, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.

Department for Life Quality Studies, University of Bologna, 40126 Bologna, Italy.

出版信息

Aging (Albany NY). 2016 Jan;8(1):147-57. doi: 10.18632/aging.100890.

Abstract

The aging process is accompanied by an accumulation of cellular damage, which compromises the viability and function of cells and tissues. We aim to further explore the association between in vitro DNA damage markers and the chronological age of the donor, as well as long-lived family membership and presence of cardiovascular diseases. Therefore, numbers of 53BP1 foci, telomere-associated foci (TAF) and micronuclei were measured in cultured dermal fibroblasts obtained from three age groups of donors (mean age 22, 63 and 90 years). Fibroblasts were cultured without a stressor and with 0.6 μM rotenone for 3 days. We found that 53BP1 foci and TAF were more frequently present in fibroblasts of old donors compared to middle-aged and young donors. No association between micronuclei and donor age was found. Within the fibroblasts of the middle-aged donors we did not find associations between DNA damage markers and long-lived family membership or cardiovascular disease. Results were comparable when fibroblasts were stressed in vitro with rotenone. In conclusion, we found that DNA damage foci of cultured fibroblasts are significantly associated with the chronological age, but not biological age, of the donor.

摘要

衰老过程伴随着细胞损伤的积累,这会损害细胞和组织的活力与功能。我们旨在进一步探究体外DNA损伤标志物与供体实际年龄之间的关联,以及长寿家族成员关系和心血管疾病的存在情况。因此,我们在来自三个年龄组供体(平均年龄分别为22岁、63岁和90岁)的培养皮肤成纤维细胞中测量了53BP1病灶、端粒相关病灶(TAF)和微核的数量。成纤维细胞在无应激源的情况下以及在含有0.6μM鱼藤酮的条件下培养3天。我们发现,与中年和年轻供体相比,老年供体的成纤维细胞中53BP1病灶和TAF更为常见。未发现微核与供体年龄之间存在关联。在中年供体的成纤维细胞中,我们未发现DNA损伤标志物与长寿家族成员关系或心血管疾病之间存在关联。当成纤维细胞在体外受到鱼藤酮应激时,结果具有可比性。总之,我们发现培养的成纤维细胞的DNA损伤病灶与供体的实际年龄显著相关,但与生物学年龄无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7171/4761719/ac542537078e/aging-08-147-g001.jpg

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