老化と神経変異は,ヒトの単一の神経細胞の変異の増加と関連しています

Michael A Lodato^1,2,3, Rachel E Rodin^1,2,3,4, Craig L Bohrson⁵

¹Division of Genetics and Genomics, Manton Center for Orphan Disease, and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA.

Science (New York, N.Y.)

|December 9, 2017

まとめ

体内の変異は歳と共にニューロンに蓄積されゲノセニウムと呼ばれるプロセスですこの蓄積は海馬で高く神経退行性疾患ではより顕著で遺伝的変化と脳の老化との関連を示唆しています

科学分野:

神経科学
遺伝学
老化に関する研究

背景:

老化と神経変性疾患は,神経細胞の体内の変異を伴うと仮定されている.
以前の研究ではこの仮説を直接検証するにあたって方法論的な課題に直面していました

研究の目的:

人間の神経細胞の老化,神経変性,体内の変異との関連を調査する.
異なる年齢と疾患状態のニューロンにおける体内単核酸変異 (sSNV) を定量化する.

主な方法:

sSNVを特定するために単細胞全ゲノム配列を解析した.
4ヶ月から82歳までの人の前頭前皮質と海馬の 161個のニューロンのDNAを分析しました
正常な老化とDNA修復障害による早期発症の神経変性 (コケイン症候群,キセロダーマ・ピグメントスウム) を含む.

主要な成果:

sSNVは,脳の両方の領域で年齢とともに線形的に増加し,ヒポカンプスではより高い割合が観察されました.
ソマティック変異は神経変性疾患を持つ個人のニューロンに多く見られた.
"ゲノセニウム"と呼ばれる体内突然変異の蓄積は,年齢に関係する,地域に関係する,および病気に関係する分子シグネチャーを示しました.

結論:

神経細胞における体内変異の蓄積 (ゲノセニウム) は,年代別年齢と脳領域に関連している.
体の変異の増加は神経変性疾患と関連しています.
ゲノセニウムは,他の年齢に関係する人間の状態に役割を果たす可能性があります.

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