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

Abstract

The 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.

Keywords: aging; biological clock; cholesterol; circadian rhythm; longevity.

Figure 1

Circadian pattern of serum cholesterol concentrations in all participants combined. Mean serum cholesterol concentrations are displayed every 30 min over a 24‐h period for all participants combined (n = 37); total cholesterol (TC) (A), HDL cholesterol (HDL‐C) (C) and non‐HDL cholesterol (non‐HDL‐C) (E) Shaded area indicates dark/sleeping period. Black arrows indicate the time of three isocaloric meals (9:00 h, 12:00 h and 18:00 h). B, D and F present the mean ± SEM serum cholesterol concentrations during the day and night period for TC, HDL‐C and non‐HDL‐C, respectively.

Figure 2

Serum cholesterol concentrations in offspring and controls. Mean serum cholesterol concentrations are displayed every 30 min over a 24‐h period stratified for offspring (n = 19; open circles) and controls (n = 18; solid circles); total cholesterol (TC) (A), HDL cholesterol (HDL‐C) (C) and non‐HDL cholesterol (non‐HDL‐C) (E). Shaded area indicates dark/sleeping period. Black arrows indicate the time of three isocaloric meals (9:00 h, 12:00 h and 18:00 h). B, D and F present the mean ± SEM serum cholesterol concentrations during the day and night period for TC, HDL‐C and non‐HDL‐C, respectively.