免疫抑制劑

 人類長生不老的秘密，藏在南太平洋神秘小島。智利復活節島的土壤中發現可抑制細胞老化的成分「免疫抑制劑」，在實驗中成功反轉自早衰症患者取得的細胞。這種成分未來將應用於抗老，以後人類或許能多活10年以上。


有「永遠年輕藥」之稱的免疫抑制劑（rapamycin），是科學家在復活節島土壤內細菌中發現的一種化學成分，目前用於抑制器官移植病患的免疫系統，避免排斥作用。

美國權威基因學家柯林斯（Francis Collins）率領的研究團隊發現，免疫抑制劑不但成功清除3名早衰症（HGPS）患者細胞內的突變蛋白質progerin，甚至有反轉老化的效果。實驗發現，免疫抑制劑可延長細胞壽命。

科學家認為，早衰症和人類老化的細胞作用相似，老化乃因人體代謝廢物的能力變差，因此這項發現可應用於抗老化研究，免疫抑制劑可能成為人類的長生不老仙丹。這項研究發表於「科學轉譯醫學」（Science Translational Medicine）期刊。

Sci Transl Med 29 June 2011:
Vol. 3, Issue 89, p. 89ra58
DOI: 10.1126/scitranslmed.3002346

• Research Article

Progeria

Rapamycin Reverses Cellular Phenotypes and Enhances Mutant Protein Clearance in Hutchinson-Gilford Progeria Syndrome Cells

1. Kan Cao¹,²,*,


2. John J. Graziotto³,*,


3. Cecilia D. Blair¹,


4. Joseph R. Mazzulli³,


5. Michael R. Erdos¹,


6. Dimitri Krainc³,† and


7. Francis S. Collins¹,†

+ Author Affiliations

1. 
   ¹Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892–8004, USA.
2. 
   ²Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
3. 
   ³Department of Neurology, Massachusetts General Hospital, MassGeneral Institute for Neurodegenerative Disease, Harvard Medical School, Charlestown, MA 02129, USA.

1. †To whom correspondence should be addressed. E-mail: francis.collins@nih.gov (F.S.C.); krainc@helix.mgh.harvard.edu (D.K.)

Abstract

Hutchinson-Gilford progeria syndrome (HGPS) is a lethal genetic disorder characterized by premature aging. HGPS is most commonly caused by a de novo single-nucleotide substitution in the lamin A/C gene (LMNA) that partially activates a cryptic splice donor site in exon 11, producing an abnormal lamin A protein termed progerin. Accumulation of progerin in dividing cells adversely affects the integrity of the nuclear scaffold and leads to nuclear blebbing in cultured cells. Progerin is also produced in normal cells, increasing in abundance as senescence approaches. Here, we report the effect of rapamycin, a macrolide antibiotic that has been implicated in slowing cellular and organismal aging, on the cellular phenotypes of HGPS fibroblasts. Treatment with rapamycin abolished nuclear blebbing, delayed the onset of cellular senescence, and enhanced the degradation of progerin in HGPS cells. Rapamycin also decreased the formation of insoluble progerin aggregates and induced clearance through autophagic mechanisms in normal fibroblasts. Our findings suggest an additional mechanism for the beneficial effects of rapamycin on longevity and encourage the hypothesis that rapamycin treatment could provide clinical benefit for children with HGPS.

Footnotes

• 
  
  ↵* These authors contributed equally to this work.
• 
  
  Citation: K. Cao, J. J. Graziotto, C. D. Blair, J. R. Mazzulli, M. R. Erdos, D. Krainc, F. S. Collins, Rapamycin Reverses Cellular Phenotypes and Enhances Mutant Protein Clearance in Hutchinson-Gilford Progeria Syndrome Cells. Sci. Transl. Med. 3, 89ra58 (2011).

• Copyright © 2011, American Association for the Advancement of Science

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