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Serum factors in older individuals change cellular clock properties

Pagani, Lucia and Schmitt, Karen and Meier, Fides and Izakovic, Jan and Roemer, Konstanze and Viola, Antoine and Cajochen, Christian and Wirz-Justice, Anna and Brown, Steven A. and Eckert, Anne. (2011) Serum factors in older individuals change cellular clock properties. Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, H. 17. pp. 7218-7223.

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Official URL: http://edoc.unibas.ch/dok/A6006489

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Abstract

Human aging is accompanied by dramatic changes in daily sleep-wake behavior: Activity shifts to an earlier phase, and the consolidation of sleep and wake is disturbed. Although this daily circadian rhythm is brain-controlled, its mechanism is encoded by cell-autonomous circadian clocks functioning in nearly every cell of the body. In fact, human clock properties measured in peripheral cells such as fibroblasts closely mimic those measured physiologically and behaviorally in the same subjects. To understand better the molecular mechanisms by which human aging affects circadian clocks, we characterized the clock properties of fibroblasts cultivated from dermal biopsies of young and older subjects. Fibroblast period length, amplitude, and phase were identical in the two groups even though behavior was not, thereby suggesting that basic clock properties of peripheral cells do not change during aging. Interestingly, measurement of the same cells in the presence of human serum from older donors shortened period length and advanced the phase of cellular circadian rhythms compared with treatment with serum from young subjects, indicating that a circulating factor might alter human chronotype. Further experiments demonstrated that this effect is caused by a thermolabile factor present in serum of older individuals. Thus, even though the molecular machinery of peripheral circadian clocks does not change with age, some age-related circadian dysfunction observed in vivo might be of hormonal origin and therefore might be pharmacologically remediable.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Erwachsenenpsychiatrie (Lang)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Erwachsenenpsychiatrie (Lang)
03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Klinische Stress- und Traumaforschung (Holsboer-Trachsler)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Klinische Stress- und Traumaforschung (Holsboer-Trachsler)
UniBasel Contributors:Cajochen, Christian and Eckert, Anne
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:National Academy of Sciences
ISSN:0027-8424
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:13 Sep 2013 07:59
Deposited On:13 Sep 2013 07:49

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