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신생아와 노인 유래 섬유아세포의 노화과정에서의 세포학적 성질의 비교

Comparison of Cellular Senescence Phenotype in Human Fibroblasts from New-born and Aged Donors.

  • 이혜원 (서울시립대학교 생명과학과) ;
  • 황은성 (서울시립대학교 생명과학과)
  • 발행 : 2008.03.31

초록

이 논문에서는 신생아와 노인 유래의 섬유아세포들의 노화의 특징들을 비교하여 사람의 나이와 세포의 수명 및 세포 형질의 관계에 대해 연구하였다. 본 연구의 결과는 비록 한가지의 노인세포에 대해 얻어진 것이기는 하지만 다음과 같은 세 가지 중요한 가능성을 제시한다. 첫째로, 노인에서 유래한 섬유아세포의 증식속도가 신생아 유래의 세포에 비해서 느릴 가능성이 있다. 이러한 결과는 실제로 노인 신체에 존재하는 세포가 신생아에 존재하는 세포에 비해 낮은 속도로 증식할 가능성을 시사하는 것으로서, 노인에서 관찰되는 조직실질의 감소 원인을 설명하는 자료가 될 수 있겠다. 둘째로, 노인 유래 섬유아세포의 early passage 세포가 신생아 유래의 세포의 early passage 세포와 동일하게 낮은 수준의 SA ${\beta}-Gal$ 활성, autofluorescence, lysosome 함량, 그리고 활성산소 수준을 갖고 있었다. 이 점은, early passage 때의 세포가 보이는 형질이 신체에 존재하는 세포의 상황과 크게 다르지 않다고 가정할 때, 노인 신체의 조직에 존재하는 세포들이 신생아의 세포와 유사한 상태로 존재할 가능성을 시사하는 것이다. 즉, 노인 신체에서는 in vitro 노화세포에서 나타나는 수준의 세포노화가 일어나 있지 않다는 것이다. 셋째, 노인세포가 노화했을 때는 신생아세포의 경우와 거의 동일한 수준의 활성산소, lysosome, SA ${\beta}-Gal$ activity 증가를 보이고 있었는데, 이는 노인 유래의 세포가 in vitro 배양 시 신생아 유래의 세포보다 더 심하거나 또는 빠른 산화적 손상이나 세포학적 변화를 겪지는 않는다는 것을 보여주는 것으로서, 세포가 보유한 항산화적 기능이 노인이 되면서 크게 약화되지는 않음을 시사하고 있다. 결론적으로 노인 유래의 세포는 세포증식 속도를 제외하면 대체로 신생아 때의 상태와 동일한 세포 내 상태를 갖고 있다고 결론 내릴 수 있겠다.

Normal somatic cells proliferate for a limited number of doublings in culture and then enter an irreversible growth-arrest state called replicative senescence. Replicative senescence has been believed a reason for the limited cellular turnover and deterioration of tissue function in aged animals. However, there is no experimental evidence supporting this assumption. Furthermore, cells from aged person have been poorly characterized with an exception of the cases of T cells. In this study, we examined cell biological changes occurring in replicative senescence of fibroblast strains originated from a new-born (NHF-NB) and a 87 year old man (NHF-87). NHF-87 (and the cells from a 75-year old) proliferated to smaller population doublings and with longer doubling times than NHF-NB did. At early passages, NHF-87 exhibited a low senescence-associated ${\beta}-Gal$ (SA ${\beta}-Gal$) activity and lipofuscin level, typical markers for cellular senescence. Furthermore, they maintained low levels of lysosome and reactive oxygen species (ROS). All of these levels increased dramatically in the late passage NHF-87 quite similarly as those in the late passaged NHF-NB did. These results indicate that most cells originated from the aged maintain a phenotype of the cells originated from new-born donors and undergo replicative senescence with the same kinetics as that of the cells from new-born. It is also indicated that not SA ${\beta}-gal$ activity but cell proliferation rate may be qualified as a biomarker for cells aged in vivo.

키워드

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