title: Serum factors in older individuals change cellular clock properties.
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.
authors.affiliation: Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric University Clinics, University of Basel, CH-4012 Basel, Switzerland.
authors.forename: Lucia
authors.initials: L
authors.lastname: Pagani
authors.forename: Karen
authors.initials: K
authors.lastname: Schmitt
authors.forename: Fides
authors.initials: F
authors.lastname: Meier
authors.forename: Jan
authors.initials: J
authors.lastname: Izakovic
authors.forename: Konstanze
authors.initials: K
authors.lastname: Roemer
authors.forename: Antoine
authors.initials: A
authors.lastname: Viola
authors.forename: Christian
authors.initials: C
authors.lastname: Cajochen
authors.forename: Anna
authors.initials: A
authors.lastname: Wirz-Justice
authors.forename: Steven A
authors.initials: SA
authors.lastname: Brown
authors.forename: Anne
authors.initials: A
authors.lastname: Eckert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D002478:Cells, Cultured; D057906:Circadian Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged
chemical_list: D036341:Intercellular Signaling Peptides and Proteins