Phenotypic and mutational spectrum of ROR2-related Robinow syndrome.

Robinow syndrome is characterized by a triad of craniofacial dysmorphisms, disproportionate-limb short stature, and genital hypoplasia. A significant degree of phenotypic variability seems to correlate with different genes/loci. Disturbances of the noncanonical WNT-pathway have been identified as the main cause of the syndrome. Biallelic variants in ROR2 cause an autosomal recessive form of the syndrome with distinctive skeletal findings. Twenty-two patients with a clinical diagnosis of autosomal recessive Robinow syndrome were screened for variants in ROR2 using multiple molecular approaches. We identified 25 putatively pathogenic ROR2 variants, 16 novel, including single nucleotide variants and exonic deletions. Detailed phenotypic analyses revealed that all subjects presented with a prominent forehead, hypertelorism, short nose, abnormality of the nasal tip, brachydactyly, mesomelic limb shortening, short stature, and genital hypoplasia in male patients. A total of 19 clinical features were present in more than 75% of the subjects, thus pointing to an overall uniformity of the phenotype. Disease-causing variants in ROR2, contribute to a clinically recognizable autosomal recessive trait phenotype with multiple skeletal defects. A comprehensive quantitative clinical evaluation of this cohort delineated the phenotypic spectrum of ROR2-related Robinow syndrome. The identification of exonic deletion variant alleles further supports the contention of a loss-of-function mechanism in the etiology of the syndrome.

Telomere Length, SIRT1, and Insulin in Male Master Athletes: The Path to Healthy Longevity?

Lower SIRT1 and insulin resistance are associated with accelerated telomere shortening. This study investigated whether the lifestyle of master athletes can attenuate these age-related changes and thereby slow aging. We compared insulin, SIRT1, and telomere length in highly trained male master athletes (n=52; aged 49.9±7.2 yrs) and age-matched non-athletes (n=19; aged 47.3±8.9 yrs). This is a cross-sectional study, in which all data were collected in one visit. Overnight fasted SIRT1 and insulin levels in whole blood were assessed using commercial kits. Relative telomere length was determined in leukocytes through qPCR analyses. Master athletes had higher SIRT1, lower insulin, and longer telomere length than age-matched non-athletes (p<0.05 for all). Insulin was inversely associated with SIRT1 (r=-0.38; p=0.001). Telomere length correlated positively with SIRT1 (r=0.65; p=0.001), whereas telomere length and insulin were not correlated (r=0.03; p=0.87). In conclusion, master athletes have higher SIRT1, lower insulin, and longer telomeres than age-matched non-athletes. Furthermore, SIRT1 was negatively associated with insulin and positively associated with telomere length. These findings suggest that in this sample of middle-aged participants reduced insulin, increased SIRT1 activity, and attenuation of biological aging are connected.

Influence of Body Fat on Oxidative Stress and Telomere Length of Master Athletes.

ABSTRACT: Aguiar, SS, Rosa, TS, Sousa, CV, Santos, PA, Barbosa, LP, Deus, LA, Rosa, EC, Andrade, RV, and Simões, HG. Influence of body fat on oxidative stress and telomere length of master athletes. J Strength Cond Res 35(6): 1693-1699, 2021-The present investigation analyzed the role of body fat and training history on biological aging of master athletes by comparing and verifying the relationships between markers of adiposity, oxidative balance, and telomere length (TL) in middle-aged runners and untrained individuals. Master athletes (sprinters and endurance runners, n = 21; 51.62 ± 8.19 years) and untrained age-matched controls (n = 11; 45.41 ± 10.34 years) had blood samples collected for biochemical and biomolecular analyzes. Pro-oxidant and antioxidant measures as well as DNA extraction were performed using commercial kits. Relative TL (T/S) was determined in leukocytes through quantitative polymerase chain reaction analyses. Master athletes had lower body fat and longer TL than untrained controls (body fat: 12.21 ± 4.14% vs. 26.03 ± 4.29%; TL: 1.10 ± 0.84 vs. 0.56 ± 0.56 T/S; p < 0.05). Furthermore, master athletes also showed a better oxidative balance than untrained controls (p < 0.05). A negative correlation was observed between TL and body fat (r = -0.471; p = 0.007), and conicity index (r = -0.407; p = 0.021), catalase activity (r = -0.569; p = 0.001), and CAT/TBARS ratio (r = -0.463; p = 0.008) for the whole sample. In conclusion, master athletes have longer TL, better oxidative profile, and lower body fat than untrained individuals. Moreover, for this middle-aged sample, body fat was inversely correlated with both TL and markers of oxidative balance, demonstrating the key role of adiposity in biological aging.

Sedentary Behavior: A Key Component in the Interaction between an Integrated Lifestyle Approach and Cardiac Autonomic Function in Active Young Men.

This study aimed to verify the association between autonomic cardiac function (CAF) and the integration of caloric expenditure by physical activity (PA) intensity, sedentary behavior (SB), and sleep quality (PSQI) in active young men. Thirty-five subjects were included, and caloric expenditure in moderate-to-vigorous and light-intensity PA, SB, and PSQI were assessed using questionnaires. Heart rate variability (HRV) was recorded for short periods of time in the supine and orthostatic positions. Multiple linear regression was realized unadjusted and adjusted for covariables, such as age, body mass index, and fat mass. No adjusted analysis indicated that, in the supine position, there were negative associations between the SB and the TP, HF, and NorHF indices, and positive associations between SB and NorLF and LF/HF. In the orthostatic position, an interaction between SB and NorLF was found. Significance of proportion with the TP, HF, and LF/HF indices was confirmed. When adjusted, for the supine position, negative interactions were documented between SB and the TP as well as the HF indices, and between PSQI and the LF/HF index, with interference under the HF and LF/HF indices. Finally, our findings indicate that the proposed approach interacts with CAF, and SB is significantly related to CAF in young active men.

Telomere length and redox balance in master endurance runners: The role of nitric oxide.

Leukocyte telomere length (LTL), a biological marker of aging that is associated with age-related diseases, is longer in master endurance runners (ER) than age-matched controls, but the underlying mechanisms are poorly investigated. The LTL, nitric oxide (NO), and redox balance of ER master runners were analyzed and compared to untrained middle-aged and young adults. We hypothesized that NO and redox balance at baseline would be related to longer LTL in ER athletes. Participants (n = 38) were long-term ER runners (n = 10; 51.6 ±â€¯5.2 yrs.; 28.4 ±â€¯9.4 yrs. of experience) and untrained age-matched (n = 17; 46.6 ±â€¯7.1 yrs) and young controls (n = 11; 21.8 ±â€¯4.0 yrs). Volunteers were assessed for anamnesis, anthropometrics, and blood sampling. Measurements of pro-and anti-oxidant status and DNA extraction were performed using commercial kits. Relative LTL was determined with qPCR analyses (T/S). While the middle-aged controls had shorter LTL than the young group, no difference was observed between ER athletes and young participants. A large effect size between the LTL of ER athletes and middle-aged controls (d = 0.85) was also observed. The ER athletes and untrained young group had better redox balance according to antioxidant/pro-oxidant ratios compared to middle-aged untrained participants, which also had lower values for redox parameters (TEAC/TBARS, SOD/TBARS, and CAT/TBARS; all p < 0.05). Furthermore, the NO level of ER athletes (175.2 ±â€¯31.9 µM) was higher (p < 0.05) than middle-aged controls (67.2 ±â€¯23.3 µM) and young participants (129.2 ±â€¯17.3 µM), with a significant correlation with LTL (r = 0.766; p = 0.02). In conclusion, ER runners have longer LTL than age-matched controls, which in turn may be related to better NO bioavailability and redox balance status.