Diabetes is a major risk factor for developing cognitive impairment and studies have shown that poor glycemic control can increase this risk, but the neural mechanisms are poorly understood. Many studies have linked altered spontaneous cortical activity during the resting-state to Alzheimer’s disease and other neurological conditions associated with cognitive impairment. Herein, we examine whether the strength of spontaneous activity during the resting-state is differentially related to glycemic control in 37 biomarker-positive participants on the Alzheimer’s disease spectrum (ADS) and 43 cognitively normal aging adults. All participants completed resting-state magnetoencephalography (MEG), a blood draw to derive their level of glycemic control (i.e., A1C), and comprehensive neuropsychological assessment. Spontaneous activity was imaged in each of the canonical frequency bands (e.g., alpha) and probed for group differences in the relationship between neural activity and glycemic control. We found significant interactions between A1C and disease status (ADS vs. control) in the delta and alpha bands (p < 0.001). Specifically, delta power decreased with increasing A1C in the ADS group across a broad area of frontotemporal and inferior parietal cortices, while spontaneous alpha decreased with higher A1C in the control group across inferior frontal and temporal cortex. Importantly, delta activity in the superior frontal cortices mediated the effect of A1C on attention performance in the ADS group. In sum, these data suggest that the impact of glycemic dysregulation on spontaneous cortical activity may differ in those on the ADS compared with cognitively normal controls and that spontaneous delta may be critical for attention function.
Adult hypothalamic neural stem and progenitor cells (htNSCs) influence aging partly through exosome-associated microRNA (miRNA) cargo, yet how their miRNA targetome relates to hypothalamic aging remains unclear. We mapped htNSC-biased miRNAs onto miRTarBase to define a 1777-gene target union and tested whether gene-level target burden aligns with public hypothalamic aging transcriptomes. The primary Spearman correlation between miRTarBase-weighted burden and GSE188646 aging log fold-change is near zero (ρ = 0.0069, P = 0.784; n = 1579 genes). Equivalence was tested at |ρ| = 0.10. That margin was fixed before the test was computed, but only after the near-zero correlation had been observed, and it was not specified before the study began. The bootstrap 95
Torque teno viruses (TTVs) are ubiquitous components of the human virome whose replication is tightly regulated by host immunity. While elevated total TTV load has been associated with increased mortality in older adults, the clinical relevance of species-level virome composition remains unclear. We profiled the circulating anellovirome in 251 hospitalized older adults using amplicon-based whole-genome sequencing and investigated associations with frailty, cognitive impairment, mortality, immune remodeling, and epigenetic aging. Reduced TTV species evenness was associated with 1-year mortality (p = 0.013, FDR = 0.052); however, differences in species composition accounted for less than 1
Cellular senescence and its associated secretory phenotype (SASP) represent a fundamental mechanism of biological aging. SASP-related inflammation has been implicated in cardiovascular disease. However, its role in perioperative risk in cardiac surgery remains largely unexplored, and established risk scores such as EuroSCORE II and the STS Score do not regard biological aging or senescence. In this prospective single-center cohort study, 131 patients aged ≥ 65 years undergoing elective cardiac surgery were enrolled. A panel of 19 preoperative SASP biomarkers was quantified by a multiplex immunoassay. Of those, 17 markers were evaluated as predictors of a composite adverse outcome, an adapted multimorbidity score with 21.4
Rapamycin, an mTOR inhibitor, continues to be investigated for hypothesized physiological, disease prevention, and longevity benefits, but few studies have been conducted in humans. Using US national organ transplant registry data, one of the largest real-world datasets examining chronic rapamycin exposure in humans, we compared the Kaplan-Meier survival age distribution of 4885 kidney transplant recipients prescribed rapamycin compared to 6589 recipients not prescribed rapamycin. Recipients were followed a median of 11 years and 6443 died during the study period. Propensity score weighting was used to adjust for exposure group differences in age, BMI, diabetes, and 15 other factors. After adjusting for demographic and clinical differences between groups, the median survival age of 64.6 years in the rapamycin group and 64.3 years in the non-rapamycin group were statistically similar (95
