Mitotic misregulation and human aging.
Messenger RNA levels were measured in actively dividing fibroblasts isolated from young, middle-age, and old-age 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.
Ly
D H
DH
Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Lockhart
D J
DJ
Lerner
R A
RA
Schultz
P G
PG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000473:pathology; D001669:Biochemical Phenomena; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000648:ultrastructure; D002648:Child; D020090:Chromosome Segregation / Q000235:genetics; D004194:Disease / Q000209:etiology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008938:Mitosis / Q000235:genetics; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011371:Progeria / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
D012333:RNA, Messenger; D014157:Transcription Factors