Hertzog Radu G
Army Center for Medical Research, CA Rosetti 37, 020012 Bucharest, Romania.
Med Hypotheses. 2006;67(1):157-60. doi: 10.1016/j.mehy.2006.01.034. Epub 2006 Mar 10.
Like cells, all mammals have a limited life span. Among cells there are a few exceptions (e.g., immortal cells), among mammals not, even if some of them live longer. Many in vitro and in vivo studies support the consensus that telomere length is strongly correlated with life span. At the somatic cellular level, long telomeres have been associated with longer life span. A different situation can be seen in immortal cells, such as cancer, germ and stem cells, where telomeres are maintained by telomerase, a specialized reverse transcriptase that is involved in synthesis of telomeres. Irrespective of telomere length, if telomerase is active, telomeres can be maintained at a sufficient length to ensure cell survival. To the contrary, telomeres shorten progressively with each cell division and when a critical telomere length (Hayflick limit) is reached, the cells undergo senescence and subsequently apoptosis. In mammals, those with the longest telomeres (e.g., mice) have the shortest life span. Furthermore, the shorter the mean telomere length, the longer the mean life span, as observed in humans (10-14 kpb) and bowhead-whales (undetermined telomere length), which have the longest mean life span among mammals. Over the past centuries, human average life span has increased. The hypothesis presented here suggests that this continual increase in the mean life span could be due to a decrease of mean telomere length over the last hundreds years. Actually, the life span is not directly influenced by length of telomeres, but rather by telomere length - dependent gene expression pattern. According to Greider, "rather than average telomere length, it is the shortest telomere length that makes the biggest difference to a cell". In the context of fast-growing global elderly population due to increase in life expectancy, it also seem to be an age related increase in cancer incidence. Nevertheless, extending healthy life span could depend on how good cells achieve, during the prenatal period and few years after birth, the equilibrium between telomere length and telomerase activity, as seen in germ cells. After all, I suggest that decrease in mean telomere length might result in, on the one hand, an increased life span and, on the other, a higher risk of tumorigenesis.
与细胞一样，所有哺乳动物都有有限的寿命。在细胞中存在一些例外情况（例如，永生细胞），而在哺乳动物中则不存在，即便有些哺乳动物寿命更长。许多体外和体内研究都支持这样一种共识，即端粒长度与寿命密切相关。在体细胞水平上，长端粒与更长的寿命相关。在永生细胞中可以看到不同的情况，如癌细胞、生殖细胞和干细胞，其端粒由端粒酶维持，端粒酶是一种参与端粒合成的特殊逆转录酶。无论端粒长度如何，如果端粒酶活跃，端粒就能维持在足够的长度以确保细胞存活。相反，端粒会随着每次细胞分裂而逐渐缩短，当达到临界端粒长度（海弗利克极限）时，细胞会经历衰老并随后凋亡。在哺乳动物中，端粒最长的那些（如小鼠）寿命最短。此外，平均端粒长度越短，平均寿命越长，如在人类（10 - 14千碱基对）和北极露脊鲸（端粒长度未确定）中观察到的那样，它们在哺乳动物中平均寿命最长。在过去几个世纪里，人类平均寿命有所增加。这里提出的假说表明，平均寿命的这种持续增加可能是由于过去几百年间平均端粒长度的缩短。实际上，寿命并非直接受端粒长度的影响，而是受端粒长度依赖性基因表达模式的影响。根据格雷德的说法，“对细胞来说，起最大作用的不是平均端粒长度，而是最短端粒长度”。在全球老年人口因预期寿命增加而快速增长的背景下，癌症发病率似乎也随年龄增长而上升。然而，延长健康寿命可能取决于细胞在产前阶段和出生后几年内如何像生殖细胞那样实现端粒长度和端粒酶活性之间的平衡。毕竟，我认为平均端粒长度的缩短一方面可能导致寿命延长，另一方面可能导致肿瘤发生风险增加。
