Biological aging alters circadian mechanisms in murine adipose tissue depots

Abstract

Biological aging alters the metabolism and volume of adipose tissue depots. Recent evidence suggests that circadian mechanisms play a role in promoting adipogenesis, obesity, and lipodystrophy.The current study compared cohorts of younger (5-9 months) and older (24-28 months) C57BL/6 mice as a function of biological age and circadian time. Advanced age significantly reduced the weight of the AGE (2013) 35:533-547 DOI 10.1007 Electronic supplementary material The online version of this article (doi:10.1007/s11357-012-9389-7) contains supplementary material, which is available to authorized users. brown, epididymal, inguinal, and retroperitoneal adipose depots but not total body weight. The older mice reduced their physical activity by >50% and delayed their activity initiation after light offset. The expressed transcriptome in brown and white adipose depots and liver of both cohorts displayed evidence of circadian rhythmicity; however, the oscillating mRNAs differed significantly between age groups and across tissues. The amplitude of Cry1, a component of the negative arm of the circadian apparatus, and downstream regulators such as Rev-erbα were elevated in the older relative to the younger cohorts as a function of circadian time. Overall, transcript levels differed significantly for 557 (inguinal adipose), 1,016 (liver), and 1,021 (brown adipose) expressed sequences between the cohorts as a function of age. These included transcripts encoding proteins within the canonical and non-canonical Wnt pathways. Since the Wnt pathway regulates adipose stem cell differentiation and shares a critical enzyme, glycogen synthase kinase 3β, with the circadian mechanism, the intersection between these two fundamental regulatory mechanisms merits further investigation with respect to biological aging of adipose tissues.

Modulation of mRNA circadian transcription cycle by microRNAs

“…Based on the new data, it is evident that the overall pattern of circadian oscillation is consistent with the previously analyzed [11,12] and reanalyzed [2,3] murine liver samples. In spite of the technological differences, as in all other microarray data sets with a similar sampling rate, the number of oscillating genes revealed by traditional, one-at-atime, independent testing was around 20% of the total number of transcripts interrogated by a particular microarray.…”

“…By using analyzed mouse liver samples collected in similar timeline experiments, but with different computational techniques [3,11,12], the current study can answer additional questions without repeating the study of Ne et al. The questions we will try to address first are the following.…”

Genome-wide circadian regulation: A unique system for computational biology

“…Biological rhythmic regulatory systems are involved in regulating metabolic processes, development, aging, and sleep [65] , [107] , [108] , [109] , [133] , [134] , [135] . Mutations in circadian genes are associated with diseases including major depressive disorder and cancer [110] , [136] , [137] .…”

Human adipose-derived stem cells cultured in keratinocyte serum free medium: Donor’s age does not affect the proliferation and differentiation capacities

“…In aged mice, an altered metabolism and volume of adipose tissue depots was observed. The weight of the brown, epididymal, inguinal, and retroperitoneal adipose depots were reduced by advanced age when total body weight was not changed [36]. …”