衰老的特征[1]描述了端粒的磨损,这是染色体保护帽的逐渐丧失。端粒磨损限制了细胞分裂的次数,慢慢导致重要器官中细胞数量的减少。

所以,什么是端粒?

储存我们遗传信息的每一条染色体在每一端都有一个保护帽,称为端粒,a specific DNA sequence that is repeated thousands of times.The sequence has two purposes: firstly,它保护染色体的编码区域并防止它们被破坏,其次,它充当一个时钟,控制一个单元可以进行的复制数量。

端粒是保护帽。

The first function is fairly simple.The building blocks of DNA are designed to bond with each other as part of their function;这可能非常有用,but because they can bond with each other,这也使得它们能够与其他分子结合,这会导致危险的后果。Two chromosomes could potentially bond together,或者染色体甚至可以和其他东西结合!

Fortunately,our cells have a solution to this problem: they use protective caps on the ends of chromosomes to prevent this from happening.These caps bond with DNA in the same way that DNA base pairs bond to each other.因此,the ends of chromosomes must be identical;如果不是这样的话,then each chromosome would need its own cap,and mutations at the end of a gene could leave a chromosome open to fraying.所以,to avoid this issue,DNA has a sequence that just signals the end of a chromosome.

DNA损伤(突变)也可以自发地改变一个碱基对到另一个碱基对。This is most likely to happen on the exposed ends of a chromosome rather than the middle,which is better protected.编码区域的损坏很难被发现和修复,因为修复机制必须知道原始的碱基对是什么。

谢天谢地,对非编码区域的损坏严重程度要小得多,with repeating sequences,far easier to repair.在这种情况下,细胞需要做的就是让修复酶检查损伤是否接近染色体末端;if a damaged sequence in this area seems close to a normal telomere sequence,端粒酶只需将序列修复回正常状态。

Finally,由于DNA的结构是如何工作的,each time a chromosome is copied,副本比父副本短一点。This means that if a coding region is shortened,it could damage the resulting protein.To prevent this,端粒作为一个一次性的代码部分,可以在细胞分裂过程中不改变功能而被移除。

Telomeres are also a clock

The second function of telomeres is to act like a "clock",and this is a bit more complex.因为端粒只是由重复的代码组成,they are easy to lengthen after being shortened by cell division.然而,this only happens in eggs,精子,大多数干细胞;常规单元格不能替换丢失的内容。This means that in normal cells,the telomeres become shorter and shorter with each subsequent cell division.Once telomeres become critically short,the cell ceases to divide and enters cellular senescence,ready to be disposed of by the immune system.

Over time,这意味着我们健康分裂细胞的储备减少,导致组织和器官功能越来越差,as there are fewer cells to replace the ones that have ceased to divide.Combined with some cells becoming senescent but avoiding apoptosis and disposal by the immune system,所有这些都说明随着年龄的增长,组织修复和维护越来越差。这就引出了一个问题:为什么所有的细胞都不能无限期地分裂?

答案是,这很可能是预防癌症的保护措施。因为端粒起着“时钟”的作用,limiting cells to a set number of replications,老化和可能受损/突变的细胞不太可能继续复制更多的突变细胞。Mutations can be harmless,but they can also be the first step on the path to a cell becoming cancerous.Cancer cells divide many more times than regular cells,having lost replicative control due to mutation,so having a system that keeps that in check is a good thing;it is likely that cancer incidence would be far higher were this system not in place.

Conclusion

It is well known that lifestyle factors,比如健康的饮食和锻炼,can reduce the rate of telomere loss.On the other hand,poor lifestyle choices,such as poor diet,sedentary lifestyle,和压力,can speed up telomere loss.

一些研究人员也在研究延长端粒的方法,though it may make more sense to replace stem cell stocks and remove senescent cells,keeping a supply of fresh cells available rather than trying to keep aged and potentially mutated cells working.这就是说,therapies that can successfully restore telomeres in specific target cell populations may prove valuable for diseases that directly affect telomeres and may potentially boost wound healing from traumatic injury.

然而,astudy by researchers at the Salk Institute revealed a possible way around this problem [2].They used reprogramming factors to "reset" the epigenetic alterations hallmark in mice and,这样做,reset the telomeres,让它们变长。所以,以这种方式清除细胞的表观遗传记忆可能是可行的,从而使其功能上再次年轻化,thus repairing a large part of its damage.This technique is similar to how scientists create induced pluripotent stem cells in the lab,which involves resetting the age of cells by removing epigenetic markers.

有许多可能的解决方案来解决这一发展中的标志,so time will tell which one proves the winner.与此同时,eat well,当我们等待这些解决方案到来时,锻炼并避免压力以保持健康。

文学类

[1] López-Otín,C.,布拉斯科MA.,Partridge,L.,Serrano,M.,克勒默G.(2013)。The hallmarks of aging.Cell,153(6),1194-1217.

〔2〕Ocampo,A.,Reddy,P.Martinez-Redondo,P.Platero-Luengo,A.,Hatanaka,F.,HishidaT.,… & Araoka,T.(2016).In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming.Cell,167(7),1719-1733.