Journal
AGING-US
Volume 8, Issue 4, Pages 642-663Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.100895
Keywords
calorie restriction; circadian rhythm; hunger; hypothalamus; transcriptomics
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Funding
- UK Biotechnology and Biological Sciences Research Council BBSRC [BB/G009953/1, BB/J020028/1]
- Centre for Genome Enabled Biology and Medicine, Aberdeen, UK
- BBSRC grant [BB/JO20028/1]
- Biotechnology and Biological Sciences Research Council [BB/M012360/1, BB/G009953/1, BB/J020028/1, 1438803] Funding Source: researchfish
- BBSRC [BB/G009953/1, BB/J020028/1, BB/M012360/1] Funding Source: UKRI
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Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti-ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin-like growth factor 1 (IGF-1), insulin, and tumor necrosis factor alpha (TNF-alpha). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF-alpha, leptin and IGF-1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes.
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