Circadian monitoring as an aging predictor.

The ageing process is associated with sleep and circadian rhythm (SCR) frailty, as well as greater sensitivity to chronodisruption. This is essentially due to reduced day/night contrast, decreased sensitivity to light, napping and a more sedentary lifestyle. Thus, the aim of this study is to develop an algorithm to identify a SCR phenotype as belonging to young or aged subjects. To do this, 44 young and 44 aged subjects were recruited, and their distal skin temperature (DST), activity, body position, light, environmental temperature and the integrated variable TAP rhythms were recorded under free-living conditions for five consecutive workdays. Each variable yielded an individual decision tree to differentiate between young and elderly subjects (DST, activity, position, light, environmental temperature and TAP), with agreement rates of between 76.1% (light) and 92% (TAP). These decision trees were combined into a unique decision tree that reached an agreement rate of 95.3% (4 errors out of 88, all of them around the cut-off point). Age-related SCR changes were very significant, thus allowing to discriminate accurately between young and aged people when implemented in decision trees. This is useful to identify chronodisrupted populations that could benefit from chronoenhancement strategies.

Impact of a shift work-like lighting schedule on the functioning of the circadian system in the short-lived fish Nothobranchius furzeri.

Adult Nothobranchius furzeri of the MZM-04/10 strain were individually kept and subjected to a "5 + 2" shifting lighting schedule (SHIFT) for 8 weeks in order to evaluate the desynchronizing effects of a simulated human-like shift-work schedule on the functioning of the circadian system (CS). With this aim, sixteen 21-week-old N. furzeri were placed into a Morning, Night and Evening schedule (lights on from 08:00 to 16:00, 00:00 to 08:00 and 16:00 to 00:00 h, respectively) and fed once a day in the middle of the corresponding photophase (12:00, 04:00 and 20:00 h, respectively). Then, in the weekends (2 days), fish were always returned to the Morning shift. As controls, 16 fish were maintained under a non-shifting LD cycle condition (CONTROL) throughout the whole experiment, with lights on from 08:00 to 16:00 h. Rest-activity rhythm (RAR) of fish subjected to SHIFT showed several symptoms of chronodisruption, such as a decrease in the percentage of diurnal activity and a reduction of the relative amplitude and the circadian function index with time. When a periodogram analysis was performed, RAR of N. furzeri under SHIFT conditions showed up to three separate circadian components: one longer than 24 h (26.5 h) that followed the weekly 8 h delays; a short-period component (~23 h) that was related to the weekend's phase advances, and finally, a 24 h component. The shifting LD schedule also affected fish CS at a molecular level, with several significant differences in the expression of core genes of the molecular clock (bmal1, clock, rorα, rev-erbα) between SHIFT and CONTROL animals. RAR impairment along with changes in clock gene expression could be associated with high stress and accelerated aging in these fish.

Age-related changes in fatty acid profile and locomotor activity rhythms in Nothobranchius korthausae.

The life cycle of Nothobranchius korthausae, a Cyprinodontiformes fish, was studied in our laboratory to characterise the ageing process. Some morphological changes, such as spine curvature, skin colour, and fin and eye appearance are described. Growth and survival curves reflected a fast life cycle with rapid initial growth until 4weeks of age, after which the fish grew more slowly before reaching their final size in week 40. Senescence onset was established at week 48 with a decrease in spawn size and viability and a general decline in the animal's appearance (weight and colouration losses, caudal fin degradation, and cataractogenesis). The fatty acid composition changed with age, with high unsaturation in the adult stage as reflected by a high peroxidation index, a condition that is associated with high susceptibility to oxidative damage if elevated reactive oxygen species (ROS) production occurs. Senescent fish had an increase in monounsaturated fatty acid proportions and a lower peroxidation index (226.5±19.7 in adults versus 120.2±19.1 in senescent fish, P<0.05). The circadian system, as reflected by locomotor activity rhythms, showed noticeable changes with age. Twenty-four-week-old fish (adults) had a robust diurnal rhythm that showed a decrease in total activity, an increase in rhythm fragmentation, and a fall in amplitude and regularity with age. Changes were clearly reflected in the Circadian Function Index variations (0.56, 0.47 and 0.25 at 24, 48 and 72weeks of age, respectively). In conclusion, N. korthausae appears to be a species with appropriate characteristics for ageing studies because it manifests clear signs of progressive ageing. Comparing species of Nothobranchius genus with different lifespans may be useful for increasing our understanding of the ageing process.