Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, Canada.
Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Aging Cell. 2022 May;21(5):e13614. doi: 10.1111/acel.13614. Epub 2022 Apr 20.
Telomerase levels in most human cells are insufficient to prevent loss of telomeric DNA with each replication cycle. The resulting "Hayflick" limit may have allowed lifespan to increase by suppressing the development of tumors early in life be it at the expense of compromised cellular responses late in life. At any given age, the average telomere length in leukocytes shows considerably variation between individuals with females having, on average, longer telomeres than males. Sex differences in average telomere length are already present at birth and correspond to reported differences in the average life expectancy between the sexes. Levels of telomerase RNA and dyskerin, encoded by DKC1, are known to limit telomerase activity in embryonic stem cells. X-linked DKC1 is expressed from both alleles in female embryo cells and higher levels of dyskerin and telomerase could elongate telomeres prior to embryo implantation. The hypothesis that embryonic telomerase levels set the stage for the sex differences in telomere length and lifespan deserves further study.
大多数人类细胞中的端粒酶水平不足以防止每个复制周期中端粒 DNA 的丢失。由此产生的“Hayflick”限制可能通过抑制生命早期肿瘤的发展来增加寿命,尽管这是以牺牲生命后期细胞反应为代价的。在任何给定的年龄,白细胞中端粒的平均长度在个体之间有很大的差异,女性的端粒通常比男性长。端粒平均长度的性别差异在出生时就已经存在,与报告的两性平均预期寿命差异相对应。端粒酶 RNA 和 DKC1 编码的 dyskerin 的水平已知会限制胚胎干细胞中端粒酶的活性。X 连锁的 DKC1 在女性胚胎细胞的两个等位基因中都有表达,较高水平的 dyskerin 和端粒酶可以在胚胎植入前延长端粒。胚胎端粒酶水平为端粒长度和寿命的性别差异奠定基础的假设值得进一步研究。