Vai trò của sự rối loạn telomere trong quá trình lão hóa và việc phát hiện nó qua các chỉ số sinh học

Springer Science and Business Media LLC - Tập 87 Số 12 - Trang 1165-1171 - 2009
von Figura, Guido1,2, Hartmann, Daniel1,3, Song, Zhangfa1, Rudolph, Karl Lenhard1
1Department of Molecular Medicine and Max-Planck-Research Group on Stem Cell Aging, University of Ulm, Ulm, Germany
2Department of Internal Medicine I, University of Ulm, Ulm, Germany
3Department of Surgery, Technical University of Munich, Ulm, Germany

Tóm tắt

Lão hóa là một quá trình phức tạp đã được chứng minh là liên quan đến sự tích lũy tổn thương DNA. Sự rút ngắn telomere đại diện cho một cơ chế nội tại của tế bào dẫn đến sự tích lũy tổn thương DNA và kích hoạt các điểm kiểm tra tổn thương DNA trong các tế bào lão hóa. Sự kích hoạt các điểm kiểm tra tổn thương DNA phản ứng với sự rối loạn telomere dẫn đến việc kích thích trạng thái lão hóa tế bào—một sự ngừng chu kỳ tế bào vĩnh viễn. Trạng thái lão hóa đại diện cho một cơ chế ức chế khối u, bảo vệ tế bào khỏi sự tiến hóa bất ổn genom và chuyển đổi. Dưới tác động tiêu cực, việc rút ngắn telomere cũng có thể hạn chế khả năng tái tạo mô và khả năng phục hồi của các mô trong phản ứng với lão hóa và bệnh mãn tính. Trong các cơ quan già, sự rút ngắn telomere cũng có thể làm tăng nguy cơ ung thư do việc khởi phát bất ổn nhiễm sắc thể, mất khả năng cạnh tranh sinh sản của các tế bào gốc già và lựa chọn các dòng tế bào phát triển bất thường. Kết quả là, những người lớn tuổi có nguy cơ cao hơn và dễ bị tổn thương bởi các bệnh khác nhau và cho thấy nguy cơ ung thư tăng cao. Gần đây, đã phát hiện ra các protein, mà được kích thích bởi sự rối loạn telomere và tổn thương DNA. Các protein này đã được chứng minh là các chỉ số sinh học mới của lão hóa và bệnh tật ở người. Tại đây, chúng tôi xem xét nền tảng khoa học và dữ liệu thực nghiệm về các chỉ số sinh học mới được phát hiện này.

Từ khóa

#lão hóa; tổn thương DNA; telomere; chỉ số sinh học; ung thư

Tài liệu tham khảo

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