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.
Highlights
During the past decades, life expectancy has increased substantially, resulting in a growing number of individuals with a high age (Oeppen & Vaupel, 2002)
Multiple polymorphisms associated with human longevity were identified in genes involved in lipid metabolism, including several apolipoproteins (e.g. APOB De Benedictis et al, 1997; APOA1 Garasto et al, 2003; APOC1 Garasto et al, 2003 and APOE Soerensen et al, 2013 which are involved in lipid transport), uncoupling protein-1, adiponectin and cholesteryl ester transfer protein
We hypothesized that human familial longevity, which is associated with a lower risk of metabolic syndrome (Rozing et al, 2010) and cardiovascular and cardiometabolic diseases at advanced middle age (Westendorp et al, 2009), is associated with a higher rhythmicity in serum cholesterol concentrations. We investigated this hypothesis by comparing circadian rhythmicity of serum cholesterol concentrations between individuals with a familial predisposition for longevity and age-matched controls
Summary
Life expectancy has increased substantially, resulting in a growing number of individuals with a high age (Oeppen & Vaupel, 2002). Familial human longevity has been associated with a less atherogenic lipid profile, which includes a larger LDL particle size (Barzilai et al, 2003), and lower circulating concentrations of triglycerides (Vaarhorst et al, 2011). Multiple polymorphisms associated with human longevity were identified in genes involved in lipid metabolism, including several apolipoproteins (e.g. APOB De Benedictis et al, 1997; APOA1 Garasto et al, 2003; APOC1 Garasto et al, 2003 and APOE Soerensen et al, 2013 which are involved in lipid transport), uncoupling protein-1 (which mediates triglyceride lowering effects through mediating thermogenesis in brown adipose tissue Rose et al, 2011), adiponectin (an antiinflammatory adipokine that increases b-oxidation and triglyceride clearance Roszkowska-Gancarz et al, 2012) and cholesteryl ester transfer protein (involved in determining the lipoprotein balance by mediating transfer of cholesteryl esters from HDL to LDL Barzilai et al, 2003; Soerensen et al, 2013). Human plasma lipid concentrations, including those of triglycerides and cholesterol, are rhythmic over a 24-h period (Rivera-Coll et al, 1994), independent of feeding and waking conditions (Chua et al, 2013)
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