Mitotic misregulation and human aging

被引：464

作者：

Ly, DH

Lockhart, DJ

Lerner, RA

Schultz, PG

机构：

[1] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[3] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA

来源：

SCIENCE | 2000年 / 287卷 / 5462期

关键词：

D O I：

10.1126/science.287.5462.2486

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Messenger RNA Levels were measured in actively dividing fibroblasts isolated from young, middle-age, and old-ago humans and humans with progeria, a rare genetic disorder characterized by accelerated aging. Genes whose expression is associated with age-related phenotypes and diseases were identified. The data also suggest that an underlying mechanism of the aging process involves increasing errors in the mitotic machinery of dividing cells in the postreproductive stage of Life. We propose that this dysfunction leads to chromosomal pathologies that result in misregulation of genes involved in the aging process.

引用

收藏

页码：2486 / 2492

页数：7

相关论文

共 47 条

[1] Atm-deficient mice: A paradigm of ataxia telangiectasia [J].

Barlow, C ;

Hirotsune, S ;

Paylor, R ;

Liyanage, M ;

Eckhaus, M ;

Collins, F ;

Shiloh, Y ;

Crawley, JN ;

Ried, T ;

Tagle, D ;

WynshawBoris, A .

CELL, 1996, 86 (01) :159-171

[2] Mutation R120G in αB-crystallin, which is linked to a desmin-related myopathy, results in an irregular structure and defective chaperone-like function [J].

Bova, MP ;

Yaron, O ;

Huang, QL ;

Ding, LL ;

Haley, DA ;

Stewart, PL ;

Horwitz, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (11) :6137-6142

[3]

BROWN WT, 1992, AM J CLIN NUTR, V55, P1222

[4]

Carlsén S, 1998, CLIN EXP IMMUNOL, V114, P477

[5] Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1 [J].

Chan, GKT ;

Schaar, BT ;

Yen, TJ .

JOURNAL OF CELL BIOLOGY, 1998, 143 (01) :49-63

[6] A genome-wide transcriptional analysis of the mitotic cell cycle [J].

Cho, RJ ;

Campbell, MJ ;

Winzeler, EA ;

Steinmetz, L ;

Conway, A ;

Wodicka, L ;

Wolfsberg, TG ;

Gabrielian, AE ;

Landsman, D ;

Lockhart, DJ ;

Davis, RW .

MOLECULAR CELL, 1998, 2 (01) :65-73

[7] IDENTIFICATION OF 9 TISSUE-SPECIFIC TRANSCRIPTION FACTORS OF THE HEPATOCYTE NUCLEAR FACTOR-III FORKHEAD DNA-BINDING-DOMAIN FAMILY [J].

CLEVIDENCE, DE ;

OVERDIER, DG ;

TAO, WF ;

QIAN, XB ;

PANI, L ;

LAI, EE ;

COSTA, RH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (09) :3948-3952

[8] Relationship between donor age and the replicative lifespan of human cells in culture: A reevaluation [J].

Cristofalo, VJ ;

Allen, RG ;

Pignolo, RJ ;

Martin, BG ;

Beck, JC .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (18) :10614-10619

[9] Osf2/Cbfa1: A transcriptional activator of osteoblast differentiation [J].

Ducy, P ;

Zhang, R ;

Geoffroy, V ;

Ridall, AL ;

Karsenty, G .

CELL, 1997, 89 (05) :747-754

[10] Cdc25 mitotic inducer targeted by Chk1 DNA damage checkpoint kinase [J].

Furnari, B ;

Rhind, N ;

Russell, P .

SCIENCE, 1997, 277 (5331) :1495-1497

← 1 2 3 4 5 →