Familial longevity is characterized by high circadian rhythmicity of serum cholesterol in healthy elderly individuals

Abstract

SummaryThe biological clock, whose function deteriorates with increasing age, determines bodily circadian (i.e. 24h) rhythms, including that of cholesterol metabolism. Dampening of circadian rhythms has been associated with aging and disease. Therefore, we hypothesized that individuals with a familial predisposition for longevity have a higher amplitude circadian serum cholesterol concentration rhythm. The aim of this study was to investigate circadian rhythmicity of serum cholesterol concentrations in offspring of nonagenarian siblings and their partners. Offspring from nonagenarian siblings (n = 19), and their partners as controls (n = 18), were recruited from the Leiden Longevity Study. Participants (mean age 65 years) were studied in a controlled in‐hospital setting over a 24‐h period, receiving three isocaloric meals at 9:00 h, 12:00 h and 18:00 h. Lights were off between 23:00 h and 8:00 h. Serum total cholesterol (TC), HDL cholesterol (HDL‐C), non‐HDL‐C and triglycerides (TG) were determined every 30 min over a 24‐h period. Serum TC concentrations were higher during day than during night in offspring (5.2 vs. 4.7 mm, P < 0.001) and in controls (5.3 vs. 5.0 mm, P < 0.001). The difference in TC concentrations between day and night tended to be greater in offspring than in controls (0.5 vs. 0.3 mm, P = 0.109), reaching statistical significance in females (P = 0.045). Notably, the day–night serum differences in non‐HDL‐C were twofold greater in offspring than in controls (0.43 vs. 0.21 mm, P = 0.044) and most explicit in females (0.53 vs. 0.22, P = 0.078). We conclude that familial longevity is characterized by a high circadian rhythmicity of non‐HDL‐C in healthy elderly offspring from nonagenarian siblings.

A Diurnal Rhythm in Brown Adipose Tissue Causes Rapid Clearance and Combustion of Plasma Lipids at Wakening

“…Participants were allowed to sleep from 2300 hr to 0800 hr, during which lights were off, and consumed identical standard liquid test meals at clock times 0900, 1200, and 1800 hr. TG levels of this cohort were reported before and were found to be rhythmic (van den Berg et al, 2017). Postprandial AUCs at 9-12 hr (3.2 ± 0.2 mM , hr) were lower compared to 12-15 hr (5.0 ± 0.3 mM , hr; p < 0.0001) and 18-21 hr (4.0 ± 0.2 mM , hr; p < 0.001) ( Figure S4).…”

“…In rodents, plasma TG and FA levels show diurnal variations reaching their lowest levels at the start of the dark, active period (Pan et al, 2010;Rudic et al, 2004;Shostak et al, 2013). We (van den Berg et al, 2017) and others (Chua et al, 2013) have shown that, also in humans, plasma lipid concentrations vary over the day, which could only partly be explained by food intake, suggesting a contribution of oscillations in the clearance of lipids by metabolic organs. We hypothesized that BAT contributes to the diurnal regulation of plasma lipids.…”

An impaired hepatic clock system effects lipid metabolism in rats with nephropathy

“…Their results are consistent with the present study; however, they did not evaluate a rhythmic component via the Fourier transform method. Significant daily variations in the HDL-C levels were detected by Rivera-Coll et al ( 48 ) and Van den Berg et al ( 49 ). However, Van Den Berg et al ( 49 ) did not evaluate a rhythmic component.…”

“…Significant daily variations in the HDL-C levels were detected by Rivera-Coll et al ( 48 ) and Van den Berg et al ( 49 ). However, Van Den Berg et al ( 49 ) did not evaluate a rhythmic component. Notably, different analytical methods in other studies make it difficult to compare the result that lack of circadian rhythm associated with HDL-C levels in the present study; a fact that may explain, in part, the observed differences in timing and daily amplitude between the present research and other studies.…”

Multi-ancestry analysis of gene-sleep interactions in 126,926 individuals identifies multiple novel blood lipid loci that contribute to our understanding of sleep-associated adverse blood lipid profile

“…We investigated SNP-sleep interactions in a large, multi-ancestry, meta-analysis of blood lipid levels. Given the growing evidence that sleep influences metabolism [39][40][41][42][43][44] HDL-c (1.00% and 0.97%) was low/modest, the novel lead SNPs identified include genes known to be associated with adiposity, inflammatory disorders, cognition, and liver function, thus identifying pathways by which sleep disturbances may influence lipid biology.…”