Circulating microRNA profile of long-lived Okinawans identifies novel potential targets for optimizing lifespan and health span.

Nonagenarians and centenarians serve as successful examples of aging and extended longevity, showcasing robust regulation of biological mechanisms and homeostasis. Given that human longevity is a complex field of study that navigates molecular and biological mechanisms influencing aging, we hypothesized that microRNAs, a class of small noncoding RNAs implicated in regulating gene expression at the post-transcriptional level, are differentially regulated in the circulatory system of young, middle-aged, and nonagenarian individuals. We sequenced circulating microRNAs in Okinawan males and females <40, 50-80, and >90 years of age accounting for FOXO3 genetic variations of single nucleotide polymorphism (SNP) rs2802292 (TT - common vs. GT - longevity) and validated the findings through RT-qPCR. We report five microRNAs exclusively upregulated in both male and female nonagenarians with the longevity genotype, play predictive functional roles in TGF-ß, FoxO, AMPK, Pi3K-Akt, and MAPK signaling pathways. Our findings suggest that these microRNAs upregulated in nonagenarians may provide novel insight into enhanced lifespan and health span. This discovery warrants further exploration into their roles in human aging and longevity.

Safety and efficacy of dynamic catheter-directed cerebral digital subtraction angiography for diagnosis of bowhunter syndrome spectrum disorders: A systematic review of the literature.

INTRODUCTION: Dynamic catheter-directed cerebral digital subtraction angiography (dcDSA) is the gold standard for diagnosing dynamic vascular occlusion syndromes such as bowhunter syndrome (BHS). Nonetheless, concerns about its safety exist and no standardized protocols have been published to date. METHODS: We describe our methodology and insights regarding the use of dcDSA in patients with BHS. We also perform a systematic literature review to identify cases of typical and atypical presentations of BHS wherein dcDSA was utilized and report on any procedural complications related to dcDSA. RESULTS: Our study included 104 cases wherein dcDSA was used for the diagnosis of BHS. There were 0 reported complications of dcDSA. DcDSA successfully established diagnosis in 102 of these cases. Thirty-eight cases were deemed atypical presentations of BHS. Fourteen patients endorsed symptoms during neck flexion/extension. In eight cases, there was dynamic occlusion of bilateral vertebral arteries during a single maneuver. Three patients had multiple areas of occlusion along a single vertebral artery (VA). An anomalous entry of the VA above the C6 transverse foramen was observed in four patients. One patient had VA occlusion with neutral head position and recanalization upon contralateral lateral head tilt. CONCLUSION: Our study highlights the safety and diagnostic benefits of dcDSA in characterizing the broad spectrum of BHS pathology encountered in clinical practice. This technique offers a powerful means to evaluate changes in cerebral blood flow and cervical arterial morphology in real time, overcoming the constraints of static imaging methods. Our findings pave the way for further studies on dcDSA to enhance cross-sectional imaging methods for the characterization of BHS and other dynamic vascular occlusion syndromes.

Novel protective effect of the FOXO3 longevity genotype on mechanisms of cellular aging in Okinawans.

The genetic association of FOXO3 genotypes with human longevity is well established, although the mechanism is not fully understood. We now report on the relationship of the FOXO3 longevity variant rs2802292 with telomere length, telomerase activity, FOXO3 expression, and inflammatory cytokine levels in men and women. In agreement with earlier work, the FOXO3 longevity variant conferred protection against telomere shortening of peripheral blood mononuclear cells from adults aged 55 years and older. This was accompanied by higher levels of telomerase activity in mononuclear cells for carriers of the longevity-associated FOXO3 G-allele of SNP rs2802292 (P = 0.015). FOXO3 mRNA expression increased slightly with age in both young (P = 0.02) and old (P = 0.08) G-allele carriers. Older female G-allele carriers displayed a modest decline in levels of pro-inflammatory cytokine IL-6 with age (P = 0.07). In contrast, older male G-allele carriers displayed an age-dependent increase in levels of anti-inflammatory cytokine IL-10 with age (P = 0.04). Thus, FOXO3 may act through several different pro-longevity mechanisms, which may differ by age and sex.

Case-based radiological anatomy instruction using cadaveric MRI imaging and delivered with extended reality web technology.

PURPOSE: Extended reality (XR) technology enhances learning in medical education. The purpose of this study was to develop and apply a case-based approach for teaching radiological anatomy utilizing XR technology for improved student exploration and engagement. METHODS: The workflow consisted of MRI scanning cadavers followed by radiological, pathological, and anatomical assessment, and finally case presentation based on XR visualizations and student interaction. Case information (Subject, History, and Physical Exam) was presented to student groups who generated and recorded hypotheses using Google Forms. RESULTS: Use of all components of the system was voluntary and a total of 74 students responded to the survey request (response rate = 95%). Assessment of the experience was conducted through a qualitative survey comprising four Likert scale questions (1-5, 1 lowest), three binary questions, and open-ended comments. Mean, standard deviation, and overall agreement (mean ± SD, OA) showed that students found MRI scans of cadavers to be helpful for dissections (4.14 ± 1.1, 74.3%) and provided an understanding of relevant anatomy (4.32 ± 0.9, 79.7%), while 78.4% of students used the DICOM viewer to visualize scans of cadavers. The difficulty of use was found to be average (2.90 ± 1.0, 23%). zSpace visualizations were used by 40.5% of students, generally agreeing that an understanding of spatial relationships improved as a result (3.60 ± 1.0, 43.2%). More case-based sessions were favored by 97.3% of students. CONCLUSIONS: Results suggest that cadaveric MRI radiological visualization and XR technology enhance understanding of case-based anatomical dissections and encourage student exploration and engagement.

Extreme longevity variants at the FOXO3 locus may moderate FOXO3 isoform levels.

The rs2802292, rs2764264 and rs13217795 variants of FOXO3 have been associated with extreme longevity in multiple human populations, but the mechanisms underpinning this remain unclear. We aimed to characterise potential effects of longevity-associated variation on the expression and mRNA processing of the FOXO3 gene. We performed a comprehensive assessment of FOXO3 isoform usage across a wide variety of human tissues and carried out a bioinformatic analysis of the potential for longevity-associated variants to disrupt regulatory regions involved in isoform choice. We then related the expression of full length and 5' truncated FOXO3 isoforms to rs13217795 genotype in peripheral blood and skeletal muscle from individuals of different rs13217795 genotypes. FOXO3 isoforms displayed considerable tissue specificity. We determined that rs13231195 and its tightly aligned proxy variant rs9400239 may lie in regulatory regions involved in isoform choice. The longevity allele at rs13217795 was associated with increased levels of full length FOXO3 isoforms in peripheral blood and a decrease in truncated FOXO3 isoforms in skeletal muscle RNA. We suggest that the longevity effect of FOXO3 SNPs may in part derive from a shift in isoform usage in skeletal muscle away from the production of 5' truncated FOXO3 isoforms lacking a complete forkhead DNA binding domain, which may have compromised functionality.

Weight-Bearing Versus Traditional Strength Assessments of the Hip Musculature.

CONTEXT: Traditional nonweight-bearing (NWB) hip-strength assessments may not directly translate to functional strength during weight-bearing (WB) activity. How NWB assessments of hip muscle strength compare with WB assessments in various positions is currently unknown. OBJECTIVE: To determine the magnitude of the differences and correlations between NWB hip strength and WB functional strength during the squatting and lunge (LNG) positions in female athletes. DESIGN: Crossover design. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Female athletes (N = 51, age = 16.2 ± 3.5 years, height = 161.5 ± 8.3 cm, mass = 58.3 ± 11.6 kg). INTERVENTION(S): Isometric resistance (N/kg) was determined for the dominant and nondominant limbs via WB assessments (squat-bilateral [legs tested simultaneously], squat-unilateral, and lunge positions) and NWB assessments (hip external rotation [HER], hip extension [HEXT], and hip abduction [HAB]). MAIN OUTCOME MEASURE(S): To compare differences between positions (P ≤ .05), we used effect sizes (d) and matched-pairs t tests, and we calculated Pearson r and R2 values. RESULTS: During the squat-bilateral on the dominant limb, females produced the most hip torque (6.13 ± 1.12 N/kg). The magnitudes of differences were very large compared with HER (3.96 ± 0.83, d = 2.2), HEXT (3.22 ± 0.69, d = 3.2), and HAB (3.80 ± 1.01, d = 2.2; all P values ≤ .01), and positions were moderately correlated (r = 0.347-0.419, R2 = 0.12-0.18). The lunge position produced the least amount of torque in the dominant limb (2.44 ± 0.48 N/kg) compared with HER (d = -2.3), HEXT (d = -1.3), and HAB (d = -1.7; all P values ≤ .001), and correlations were small to moderate (r = 0.236-0.310, R2 = 0.06-0.10). CONCLUSIONS: Strength in WB positions was different than strength evaluated using traditional NWB assessments in female athletes. Weight-bearing tests may provide clinicians with additional information regarding strength and function.

Minimal Shortening of Leukocyte Telomere Length Across Age Groups in a Cross-Sectional Study for Carriers of a Longevity-Associated FOXO3 Allele.

FOXO3 is one of the most prominent genes demonstrating a consistently reproducible genetic association with human longevity. The mechanisms by which these individual gene variants confer greater organismal lifespan are not well understood. We assessed the effect of longevity-associated FOXO3 alleles on age-related leukocyte telomere dynamics in a cross-sectional study comprised of samples from 121 healthy Okinawan-Japanese donors aged 21-95 years. We found that telomere length for carriers of the longevity associated allele of FOXO3 single nucleotide polymorphism rs2802292 displayed no significant correlation with age, an effect that was most pronounced in older (>50 years of age) participants. This is the first validated longevity gene variant identified to date showing an association with negligible loss of telomere length with age in humans in a cross-sectional study. Reduced telomere attrition may be a key mechanism for the longevity-promoting effect of the FOXO3 genotype studied.