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trends in CELL BIOLOGY (Vol. 10) July 2000 273

Every field has a favourite and, in cellbiology, the centrosome has alwaysbeen on the top of many a researcher’slist. The centrosome organizes micro-tubules and is found in a juxtanuclearposition during interphase and at thepoles of mitotic spindles. Centrosomesconsist of a pericentriolar matrix, whichnucleates the microtubules; at theircentre are two barrel-shaped entities0.5 mm in length called centrioles. Thefunction of centrioles is unknownbesides that, without them, vertebratecells seem unable to divide. How orwhen during the cell cycle these tinycentrioles assemble are also unan-swered questions; previous EM studieshave shown that one of the two centri-oles is the older and therefore called the‘mother’ – the other, younger, centrioleis called the ‘daughter’.

The centriole-duplication processbegins at the G1–S phase, where a smallprotrusion on the mother centriole isobserved; it takes about 1.5 cell cyclesto form a mother centriole. Until thestudy by Piel et al.1, there were nodynamic descriptions of how themother and daughter centriole behaveduring the cell cycle and whether theyare functionally distinct; this wasbecause all previous studies were per-formed by electron microscopy, whichrequires fixation. By using green-fluor-escent protein (GFP)-labelled centrin,which binds to centrioles, it was poss-ible, for the first time, to follow eachindividual centriole in real-time1.

The three major findings are: first, sur-prisingly, the daughter centriole movesin a maturation-dependent and micro-tubule- and actin-dependent way,

whereas the mother centriole shows nomovement at all, second, the juxtanu-clear position of the centrosome doesnot require the nucleus and is mediatedby microtubules, and, third, both cen-trioles seem to nucleate microtubules intheir vicinity, whereas only the mothercentriole anchors them (possibly in aninein-dependent way).

This work clearly shows that the activityof each centriole is different and matu-ration-dependent; the importance ofthese differences for the cell is unknownbut probably involves processes such ascytokinesis and cell motility1.

Daughter centrioles on the move

1 Piel, M. et al. (2000) The respectivecontributions of the mother anddaughter centrioles to centrosomeactivity and behavior in vertebrate cells.J. Cell Biol. 149, 317–329

answer to the question of whethergenomic instability or a transcrip-tional defect underlies Cockaynesymptoms remains elusive. In eithercase, it will be interesting to seewhether ‘jamming the transcriptionmachinery’ is also implicated in theprocess of human aging.

1 le Page, F. et al. (2000) Transcriptioncoupled repair of 8-oxoguanine:requirement of XPG, TFIIH, and CSB and implications for Cockayne syndrome. Cell 101,159–171

2 Berneburg, M. et al. (2000) UVdamage causes uncontrolled DNAbreakage in cells from patients withcombined features of XP-D andCockayne syndrome. EMBO J. 19,1157–1166

The causes of aging are not wellknown, although there is some evi-dence suggesting the involvement oftelomere shortening, mitochondrialmutations and chromosomal abnor-malities related to the accumulation ofoxidative damage in cells. In a reportby Ly and colleagues1, the causes ofaging were investigated by studyingfibroblast cell lines derived from normalyoung (NY), middle-age (NM) and old-age (NO) humans, and humans withprogeria (P, a genetic disease withaccelerated aging) in culture.

The authors observed that, instead ofthe elliptical morphology characteristicof NY and NM fibroblast nuclei, manyNO and P fibroblasts had multiplenuclei, multilobed nuclei or their nu-clear boundaries were irregular. In addi-tion, many NO and P fibroblasts had a4N (tetraploid) DNA content. Followingthis up, they used oligonucleotide

arrays containing probes for more than6000 known human genes to examinemRNA levels in NY, NM, NO and Pfibroblasts. The level of changes werecompared with the NY mRNA expres-sion level as the baseline. In comparingNY and NM samples, they found thatabout 1% of the number of genesshowed changes in the mRNA expres-sion level. Most of these gene productswere involved in cell-cycle progressionand regulation of the extracellularmatrix. Some others were related tokey enzymes involved in the conver-sion of arachidonic acids to theprostaglandins and thromboxane. Incomparing NY and NO, a similar pat-tern of downregulation of genesinvolved in G2–M phase of the cellcycle was observed. Many of the genescompared in NY and P also showed apattern of changes similar to those inNY versus NO. Comparison of NO and

P cells also revealed a number of genesthat might be specifically related toaging. For example, COX-2 expressionwas downregulated in NO and P, tally-ing with findings with COX-2-knock-out mice, which were previously foundto have aging-related abnormalities,such as renal dysplasia and cardiacfibrosis.

However, these changes in fibroblastsrelated to aging were not the same asthose found in other cell types, such asskeletal muscle cells, that were studiedpreviously. Considering the role offibroblasts in skin renewal, the loss ofcellular regeneration capacity might beone of the contributing factors inaging.

Secrets of youth: the age-old question

1 Ly, D.H. et al. (2000) Mitoticmisregulation and human aging.Science 287, 2486–2492