Earlier Acrophase Research Articles

CARDIORESPIRATORY FITNESS IS ASSOCIATED WITH CIRCADIAN BEHAVIORAL PARAMETERS OF PHYSICAL ACTIVITY IN OLDER ADULTS

Abstract Cardiorespiratory fitness (VO2peak) declines with age, and this may be due in part to weakened circadian functions. Rhythmic patterns of rest-activity behavior over 24h represents a novel feature of physical activity, indicative of circadian behavior. Whether VO2peak relates to rest-activity rhythms (RAR) is unknown. We determined cross-sectional associations between VO2peak and RAR in SOMMA (N=714, Age: ≥70 yrs). Activity data from wrist-worn accelerometry (ActiGraph GT9X) were collected in one-minute epochs, over 8, 24h periods. An extension to the traditional cosine model was used to map RAR to activity data, calculating these parameters: strength of the rhythm (amplitude); robustness of rhythm (pseudo-F statistic); and timing of peak activity (acrophase). RAR parameters were expressed as quartiles. Linear models examining associations of RAR and VO2peak were adjusted for potential confounders (age, race, height, comorbidities and lifestyle). Interactions of RAR predictors with sex were examined. Associations between VO2peak and rhythmic amplitude appears to differ by sex (p-interaction=0.07). Among men, VO2peak was positively associated with amplitude (adjusted mean Q1: 21.3 vs. Q4: 23.9, p-trend=0.005)-even after adjusting for moderate-to-vigorous physical activity levels (MVPA)-although associations were more modest and not significant in women. Those with higher VO2peak had an earlier acrophase (time of peak activity) (adjusted mean: Q1 <1:30PM: 21.0 vs. Q4>3:09PM 19.3, p-trend <0.0001) and no sex interaction was observed. There were no associations between the robustness of RAR and VO2peak. Analyses reveal that better cardiorespiratory fitness relates to features of circadian behavior independent of MVPA, supporting emerging research that circadian-based interventions promote healthy aging.

CROSS-SECTIONAL AND LONGITUDINAL RELATIONSHIPS BETWEEN REST-ACTIVITY RHYTHMS AND INFLAMMATION IN OLDER MEN

Sleep disturbances and physical inactivity have been associated with chronic inflammation, an important risk factor for cognitive decline in the aging population. However most previous studies focused on the cross-sectional relationships between sleep and physical activity and inflammation. In the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study, we studied both the cross-sectional and prospective associations between characteristics of 24-hour rest-activity rhythms measured by actigraphy and inflammation index measured by multiple circulating markers. In cross-sectional analysis, a lower amplitude is associated with elevated inflammation (Odds ratio Q4 vs Q1 (95% Confidence interval): 1.65 (1.22, 2.24)). In prospective analysis, an earlier acrophase (<12:30) is associated with a two-fold increase in the risk of developing elevated inflammation over four years of follow up (2.08 (1.02, 4.23)). No individual inflammatory markers are associated with rest-activity rhythms. Our findings suggest that rest-activity rhythm characteristics predicts elevated inflammation.

Sex differences in diurnal rhythms of food intake in mice caused by gonadal hormones and complement of sex chromosomes

We measured diurnal rhythms of food intake, as well as body weight and composition, while varying three major classes of sex-biasing factors: activational and organizational effects of gonadal hormones, and sex chromosome complement (SCC). Four Core Genotypes (FCG) mice, comprising XX and XY gonadal males and XX and XY gonadal females, were either gonad-intact or gonadectomized (GDX) as adults (2.5months); food intake was measured second-by-second for 7days starting 5weeks later, and body weight and composition were measured for 22weeks thereafter. Gonadal males weighed more than females. GDX increased body weight/fat of gonadal females, but increased body fat and reduced body weight of males. After GDX, XX mice had greater body weight and more fat than XY mice. In gonad-intact mice, males had greater total food intake and more meals than females during the dark phase, but females had more food intake and meals and larger meals than males during the light phase. GDX reduced overall food intake irrespective of gonad type or SCC, and eliminated differences in feeding between groups with different gonads. Diurnal phase of feeding was influenced by all three sex-biasing variables. Gonad-intact females had earlier onset and acrophase (peak) of feeding relative to males. GDX caused a phase-advance of feeding, especially in XX mice, leading to an earlier onset of feeding in GDX XX vs. XY mice, but earlier acrophase in GDX males relative to females. Gonadal hormones and SCC interact in the control of diurnal rhythms of food intake.

Temporal profiles of physical activity and energy expenditure in cancer in-patients

Fifty-three cancer in-patients (37 males and 16 females) were randomly selected from the Regional Cancer Center, Pt. J.N.M. College, Dr. B.R. Ambedkar Hospital, Raipur, India. Rhythms in physical activity (PA) and energy expenditure (EE) were studied non-invasively using Actical (Mini Mitter Co. Inc., USA) and compared with 24 apparently healthy subjects (11 males and 13 females). Data were gathered at 1-min epoch length for at least three to four consecutive days and were analyzed using several statistical techniques, such as Cosinor rhythmometry, ANOVA, Duncan's multiple-range test, and t-test. Most of the cancer in-patients and all control subjects exhibited a statistically significant circadian rhythm in PA and EE. However, the rhythm detection ratio was low among cancer in-patients. Patients had significantly lower 24-h average, lower amplitude, and an earlier acrophase in PA and EE rhythms. Further, significant effect of factor disease was discerned on total activity count (TAC) and total energy expenditure (TEE). TAC and TEE were significantly lower in cancer in-patients as compared to control subjects, irrespective of gender. In addition, a gradual decrement in PA intensity levels from sedentary to vigorous was validated in patients. From the present findings, it can be concluded that the factor disease might alter the temporal profiles of the PA and EE. However, further intensive studies involving more patients are required to reinforce the above conclusion.

Thyrotropin Secretion in Mild and Severe Primary Hypothyroidism Is Distinguished by Amplified Burst Mass and Basal Secretion with Increased Spikiness and Approximate Entropy

Twenty-four-hour TSH secretion profiles in primary hypothyroidism have been analyzed with methods no longer in use. The insights afforded by earlier methods are limited. We studied TSH secretion in patients with primary hypothyroidism (eight patients with severe and eight patients with mild hypothyroidism) with up-to-date analytical tools and compared the results with outcomes in 38 healthy controls. Patients and controls underwent a 24-h study with 10-min blood sampling. TSH data were analyzed with a newly developed automated deconvolution program, approximate entropy, spikiness assessment, and cosinor regression. Both basal and pulsatile TSH secretion rates were increased in hypothyroid patients, the latter by increased burst mass with unchanged frequency. Secretory regularity (approximate entropy) was diminished, and spikiness was increased only in patients with severe hypothyroidism. A diurnal TSH rhythm was present in all but two patients, although with an earlier acrophase in severe hypothyroidism. The estimated slow component of the TSH half-life was shortened in all patients. Increased TSH concentrations in hypothyroidism are mediated by amplification of basal secretion and burst size. Secretory abnormalities quantitated by approximate entropy and spikiness were only present in patients with severe disease and thus are possibly related to the increased thyrotrope cell mass.

Chronomics reveal and quantify circadian rhythmic melatonin in duodenum of rats

A circadian rhythm is documented in duodenal melatonin in rats, peaking 16.8 hours after light onset. This component is more readily detected after log10-transformation of the data. It differs between male and female rats, females having a larger circadian amplitude and an earlier acrophase. The circadian rhythm in duodenal melatonin is also found to lead that of pineal melatonin. The results are qualified by the presence at the start of mapping of the second extremum of a double magnetic storm.

The relationship between dementia severity and rest/activity circadian rhythms

Patients with dementia have been shown to have disturbed sleep/wake rhythms. There is evidence of impairment in endogenous generation of rhythms and deficient environmental cues in this population. This study sought to examine patterns of rest/activity rhythms as they relate to dementia severity. Three days of actigraphy were collected from 150 nursing-home patients with dementia and used to compute rhythm parameters. Dementia severity was estimated with the Mini-Mental State Examination (MMSE). The relationship between rhythm parameters and dementia severity was examined. Rhythm parameters were not associated with dementia in the sample as a whole, but relationships emerged when the sample was divided on the basis of overall rhythm robustness (F-statistic). Within the group with less robust rhythms, those with stronger rhythms had less severe dementia. In the group with more robust rhythms, milder dementia was associated with having an earlier acrophase (timing of the peak of the rhythm) and narrower peak of the rhythm (shorter duration of peak activity). These results suggested a three-stage model of rest/activity rhythm changes in dementia in which dementia patients have a rapid decline in rhythmicity followed by a slight return to stronger rhythms. In the later stages of dementia, rhythms decline even further.

Twenty-four—hour variation in serum leptin in the elderly

To investigate the possibility that the aging process may affect the diurnal variation in serum leptin in humans, serum leptin levels were measured by a sensitive radioimmunoassay method in 12 elderly (aged 72 to 87 years) and 10 middle-aged (35 to 50 years) lean male subjects. Fasting blood samples (4 mL) were drawn at 8:00 AM, and then every 4 hours until 10:00 PM and every 2 hours from 12:00 midnight to 8:00 AM of the next morning. Circadian rhythmicity analysis was performed using the cosinor method. In elderly subjects, serum leptin levels showed a significant diurnal rhythm, which was similar to that observed in controls. Single cosinor analysis showed a significant rhythm in eight of 12 elderly subjects and in all middle-aged subjects but one. Compared with middle-aged subjects, similar mesor mean values (7.8 ± 1.0 v 8.1 ± 0.8 ng/mL) but a decreased amplitude (1.4 ± 0.3 v 2.3 ± 0.2 ng/mL) and an earlier acrophase (11:56 PM v 2:04 AM) were observed in the elderly. The data demonstrate that the diurnal variation in serum leptin is generally preserved in the elderly. However, the amplitude of leptin diurnal excursion undergoes a reduction with advancing age. It can be speculated that the blunted diurnal variation in serum leptin observed in the elderly may result in an alteration of the afferent signal in the adipose tissue—central nervous system homeostatic loop.

Twenty-four hour melatonin pattern in acromegaly: effect of acute octreotide administration.

We investigated the melatonin (MT) circadian rhythm before and after somatostatin (octreotide) acute administration in ten subjects (4 M, 6 F. 23-52 yr old) with active acromegaly due to pituitary microadenoma. Blood samples were drawn every 2 hours over a 48-h span; after 24-h basal blood collection, octreotide (Sandostatin, Sandoz) 100 micrograms sc/8 h was administered. As control, 7 healthy adult subjects (3M, 4F; 26-50 yr old) were studied in basal condition over a 24-h span. Plasma MT and GH levels were measured by RIA in each sample, IGF-1 levels were measured by immunoradiometric assay in basal and after octreotide morning samples. The comparisons were made by Mann-U-Withney and Wilcoxon test as appropriate; the existence of a MT circadian rhythm was validated by cosinor analysis; GH and MT values were correlated by Pearson's correlation coefficient. All of 7 control subjects and 2 of 10 acromegalics had significant 24-h MT rhythm. The area under curve (AUC), mesor and amplitude of the MT rhythms in acromegalics were significantly lower than in the controls (p < 0.001, 0.002 and 0.0006, respectively), with an earlier acrophase (median value: 22:14 vs 02:08 h of controls). Basal plasma IGF-1 levels and circadian GH concentrations were significantly increased in acromegalics in comparison with the control group. Octreotide administration significantly reduced GH, restoring a circadian MT rhythm in 5 of 10 acromegalics, with MT mean mesor and AUC not different from controls. Mean amplitude still remained lower than controls (p < 0.0006), with an earlier acrophase (median 00:01 h). No significant correlation was found between individual GH and MT levels. Our data indicate a reduction of MT circadian secretion in acromegaly, due especially to a blunted nocturnal increase with earlier MT peak; moreover, acute octreotide administration increase MT levels without modifying amplitude and phase of night-time secretion significantly. These findings suggest a negative interrelationship between GH and MT secretions or a facilitatory influence of somatostatin on daytime MT release only. This partial recovery of pineal secretion after octreotide in acromegalics could be a clinically significant contribution to improve their quality of life, considering that MT is involved in the regulation of several important functions.

Individual differences in circadian rhythm parameters and short-term tolerance to shiftwork: a follow-up study.

The relationship between individual differences in the phase and amplitude of circadian rhythms and tolerance to shiftwork has been the subject of several studies. Those studies recorded circadian rhythms and shiftwork tolerance at approximately the same time. The present study aimed to examine the predictive relationships between the amplitude, phase, and mesor of 24 h rhythms obtained before exposure to shiftwork, and subsequent indices of tolerance measured after one and three years of shiftwork. The results revealed some stable relations between the various rhythm parameters and subsequent tolerance measures. Workers who had a higher mesor of positive moods, and a lower mesor of negative moods and fatigue, before entering shiftwork tended to tolerate shiftwork better. Further, those whose heart rate rhythm showed an earlier acrophase had better subsequent sleep quality scores, while those with a smaller amplitude of their temperature, negative mood and fatigue rhythms showed better night-shift tolerance.

Apparent phase advance in diurnal MHPG rhythm in depression.

Several investigators have proposed that diurnal rhythms, particularly that of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), show abnormalities in affective disorders. The present study compared diurnal MHPG rhythms in the plasma of 18 male depressed patients and 12 healthy male volunteers. A diurnal rhythm of MHPG closely fit to a cosine model was observed in volunteers and, to a lesser extent, in depressed patients. Patients, especially those with endogenous depression (N = 11), demonstrated an earlier acrophase (mean +/- SD = 12.53 +/- 3.38 hours), and treatment with desipramine was associated with a significant (3-hour) phase delay. This study confirms and extends previous reports of apparent phase advances in circadian noradrenergic rhythms in depressed patients.