Circadian period of luciferase expression shortens with age in human mature adipocytes from obese patients

Abstract

Daily rhythms in physiology and behavior change with age. An unresolved question is to what extent such age-related alterations in circadian organization are driven by the central clock in the suprachiasmatic nucleus (SCN), modifying timing signals to contributing peripheral tissue oscillators, and are mediated by underlying changes in the local cellular oscillators themselves. Using a bioluminescence reporter approach, we sought to determine whether circadian clock function in human adipocytes from subcutaneous (SAT) and visceral (VAT) adipose tissues changeswith age. SAT andVAT biopsies were obtained from obese individuals during gastric bypass surgeries [n = 16; body mass index: 44.8 6 11.4 kg/m2; age: 44 6 9 yr (range: 30-58)]. Cells were isolated and transduced with a lentiviral circadian reporter construct [brain and muscle aryl hydrocarbon receptor nuclear translocator-like:luciferase (BMAL:LUC)], and bioluminescence was recorded over a period of 3 d. Human BMAL1:LUC adipocytes displayed a robust luminescence rhythm with comparable within-individual periods in mature and preadipocytes (P > 0.05).With increasing age, the circadian period decreased in mature adipocytes (P = 0.005) (b = 4 min/yr; P < 0.05). Our ex vivo approach indicated that ageing changes the organization of endogenous circadian oscillators in human adipocytes, independent of SCNsignaling.