端粒在瓢體蟲前端再生及老化過程中的恆定

Abstract

端粒(Telomere)是一段存在於真核生物染色體末端的功能性結構，它能避免染色體降解與不正常融合的發生。隨著細胞分裂的進行，無法完全複製的端粒DNA將逐漸縮短。研究已經指出，許多老化相關的疾病與過短的端粒有著密不可分的關係。因此，端粒耗損(Telomere attrition)已被認為是造成生物衰老的一個影響因子。端粒酶具有延長端粒的功能，並且在特定組織中避免端粒縮短的情形發生。眾多研究發現，在組織的更新及再生過程中端粒必須維持一定的長度以確保細胞分裂得以進行。因此，端粒酶的功能可能在其中扮演關鍵角色。一般認為生物的再生能力會隨著老化的過程而下降，然而對於老化如何透過端粒與端粒酶的調控來影響再生進行，目前尚未徹底了解。瓢體蟲(Aeolosoma viride)是一種小型淡水生環節動物，其具有優異的再生能力與相對較短的壽命，因此適合作為研究該問題的實驗材料。在本研究中，瓢體蟲的端粒DNA序列TTAGGG已被清楚辨識，有助於後續測量端粒的長度變化，其端粒酶基因(Avi-tert)亦被成功選殖以作為基因表現的指標。研究結果顯示，端粒酶的酵素活性可在蟲體的頭部、軀幹及尾部被偵測到，因此端粒酶基因可能常態表現於瓢體蟲體內。此外，在前端再生的過程中，再生區域內的端粒酶基因表現與活性有顯著地上升，同時端粒長度亦維持不變，這表示端粒酶確實參與再生的過程。最後，追蹤端粒酶活性及端粒長度在老化過程中的變化，結果顯示兩者在老化的過程中並無減少或變短的情形。這些結果說明，端粒酶參與瓢體蟲的再生過程使端粒維持恆定，此外瓢體蟲的衰老、死亡並不是端粒耗損所造成的結果。

Telomeres are the functional chromosome elements which protect the ends of eukaryotic linear chromosomes from degradation and fusion. Incomplete telomere DNA replication results in length shortening following each cell division. It has been reported that shortened telomeres are involved in several age-related diseases. For that reason, telomere attrition is considered as one of the aging factors. Telomerase extends telomere ends to prevent telomere shortening in certain tissues. More and more studies suggest that telomere maintenance is necessary in tissue renewal and regeneration. Therefore, telomerase activation may play a pivotal role during these processes. In general, regeneration ability is compromised in aged individuals. However, it is unclear how aging affects regeneration process and whether it is through the regulation of telomere maintenance and telomerase activation in an organism. Aeolosoma viride is a fresh water annelid with strong regeneration ability. Because of its short lifespan, A. viride would be a suitable species to address this question. In the present study, the telomeric sequence, TTAGGG, in A. viride has been identified, and the telomerase reverse transcriptase gene, Avi-tert, has been cloned. Avi-tert may be constitutively expressed because telomerase activity could be detected in head, trunk, and tail regions of intact animal. Besides, during anterior regeneration, both Avi-tert expression and telomerase activity were significantly upregulated at the regenerating site where telomere length was maintained. These results suggest that although telomerase is constitutively expressed, a boost of gene expression and enzyme activity are required during the regeneration process in A. viride. Furthermore, it was found that telomere length and telomerase activity were both maintained during A. viride lifespan, which supports the unexpected scenario that telomere attrition may not be an aging factor in A. viride. All in all, aging is a multifaceted process, and more investigations are required to clarify its influence on regeneration.