Nakamura Ken-Ichi, Takubo Kaiyo, Izumiyama-Shimomura Naotaka, Sawabe Motoji, Arai Tomio, Kishimoto Hiroshi, Fujiwara Mutsunori, Kato Motonobu, Oshimura Mitsuo, Ishii Akio, Ishikawa Naoshi
Research Team for Geriatric Diseases, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
Exp Gerontol. 2007 Oct;42(10):944-50. doi: 10.1016/j.exger.2007.05.003. Epub 2007 May 21.
Many studies have demonstrated the association between telomere length in mitotic cells and carcinogenesis and mortality, but little attention has been focused on post-mitotic cells and human life expectancy. We assessed the relationship between telomere length in cerebral gray and white matter and longevity in 72 autopsied Japanese patients aged 0-100 years using Southern blot hybridization. The mean telomere lengths in the gray and white matter were 12.3+/-2.5 kilobase pairs and 11.4+/-2.1 kilobase pairs, respectively. The mean telomere lengths in 60-69 year decadal group were less than those of neonates, and declined further in the 70-79-year age group, but those in groups of further advanced age were longer than in the 70-79 year group (70-79<80-89<90-100 years of age). Thus, the 90-100-year age group possessed significantly longer telomeres than the 70s (p=0.029). Autopsy protocols showed a decrease in the rate of cancer death in individuals in their 80s (p=0.041) and 90s (p=0.017) versus those in their 60s, and in their 80s the mean telomere length in the gray matter from cancer death patients was significantly shorter than that of patients who died of other diseases (p=0.04). These data suggest that innate telomere lengths are maintained very well in the cerebrum, and are associated with longevity. Our study lends indispensable support to the hypothesis that longer telomeres protect the genome from instability (a major cause of carcinogenesis) and are beneficial for longevity.
许多研究已经证实有丝分裂细胞中的端粒长度与致癌作用和死亡率之间存在关联,但对于有丝分裂后细胞和人类预期寿命的关注却很少。我们使用Southern印迹杂交技术评估了72例年龄在0至100岁之间的日本尸检患者脑灰质和白质中的端粒长度与寿命之间的关系。灰质和白质中的平均端粒长度分别为12.3±2.5千碱基对和11.4±2.1千碱基对。60 - 69岁十年组的平均端粒长度小于新生儿组,在70 - 79岁年龄组中进一步下降,但年龄更大组的端粒长度比70 - 79岁组更长(70 - 79<80 - 89<90 - 100岁)。因此,90 - 100岁年龄组的端粒明显长于70多岁组(p = 0.029)。尸检记录显示,80多岁(p = 0.041)和90多岁(p = 0.017)的个体与60多岁个体相比,癌症死亡率有所下降,并且在80多岁时,癌症死亡患者灰质中的平均端粒长度明显短于死于其他疾病的患者(p = 0.04)。这些数据表明,大脑中先天性端粒长度保持得非常好,并且与寿命相关。我们的研究为更长的端粒保护基因组免受不稳定性(致癌作用的主要原因)影响并有利于长寿这一假说提供了不可或缺的支持。