👤 Zbigniew Jost

Cognitive decline during aging may be influenced by peripheral factors, including neuroproteins and pro-inflammatory cytokine levels, body composition, and physical fitness. However, the specific associations between these factors and cognitive performance remain underexplored. A comprehensive assessment, including peripheral cytokine and neuroprotein levels, body composition, physical performance (aerobic fitness and muscle strength), and cognitive function was performed in a cohort of 87 older adults (mean age: 69.3 ± 3.4 years; 66 females, 21 males) with a range of Body Mass Index (BMI): 19.7 - 41.9. Elevated blood levels of N-lactoyl-phenylalanine (Lac-Phe) were associated with better psychomotor speed (r = -0.223, p = 0.034) as measured by the Trial Making Test-A (TMT-A). Elevated pro-inflammatory cytokines (IL-6, IL-8, IL-12) and peripheral clusterin concentrations were also associated with poorer cognitive performance. No significant associations were found between cortisol, brain-derived neurotrophic factor and cognitive function. BMI and fat mass (kg) were positively associated with performance on the Stroop Test, suggesting a negative effect of increased adipose tissue on inhibitory control. In contrast, greater skeletal muscle mass was positively associated with better memory. Physical fitness parameters, including VO Show less

In contemporary research practice, high-intensity interval training (HIIT) has received growing attention compared to other types of endurance training [e.g., moderate-intensity continuous training (MICT)]. This is primarily related to HIIT's ability to induce higher metabolic stress, driving an increased exerkine secretory response (i.e., of specific proteins) compared to MICT. To date, previous reviews on HIIT have primarily focused on single exerkines, while a more comprehensive analysis, as required to gain a more comprehensive understanding of the complex exercise-related physiological processes, is absent. To reduce non-exercise protocol-related outcome heterogeneity, the rigorous inclusion criteria (i.e., exercise intensity in the HIIT adjusted for the target population of healthy, diseased, or older individuals, and not taking any medications) were applied. A total of 39 studies were selected for the systematic review, with fourteen, twenty-two, and three for the acute, chronic, and both acute and chronic effects of HIIT on exerkine concentrations, respectively. Acute HIIT appears to result in greater changes in BDNF and VEGF concentration than the control group performing lower-intensity exercise or no exercise. Metabolically active exerkine, such as adiponectin, mainly fluctuates among overweight and obese participants. This systematic review did not yield any definitive results regarding alterations in IGF-1, irisin, cortisol, and interleukin levels. Tendentially, HIIT is more effective than MICT and non-exercise interventions to induce a greater secretory response of certain exerkines, such as BDNF, VEGF and adiponectin. Evidence regarding exerkine secretion in response to HIIT among older adults remains limited, highlighting the need for further investigation. Identifier CRD420251003743. Show less

Mice lacking the bHLH transcription factor (TF) Neurog3 do not form pancreatic islet cells, including insulin-secreting beta cells, the absence of which leads to diabetes. In humans, homozygous mutations of NEUROG3 manifest with neonatal or childhood diabetes. Despite this critical role in islet cell development, the precise function of and downstream genetic programs regulated directly by NEUROG3 remain elusive. Therefore, we mapped genome-wide NEUROG3 occupancy in human induced pluripotent stem cell (hiPSC)-derived endocrine progenitors and determined NEUROG3 dependency of associated genes to uncover direct targets. We generated a novel hiPSC line (NEUROG3-HA-P2A-Venus) where NEUROG3 is HA-tagged and fused to a self-cleaving fluorescent VENUS reporter. We used the CUT&RUN technique to map NEUROG3 occupancy and epigenetic marks in pancreatic endocrine progenitors (PEP) that were differentiated from this hiPSC line. We integrated NEUROG3 occupancy data with chromatin status and gene expression in PEPs as well as their NEUROG3-dependence. In addition, we investigated whether NEUROG3 binds type 2 diabetes mellitus (T2DM)-associated variants at the PEP stage. CUT&RUN revealed a total of 863 NEUROG3 binding sites assigned to 1263 unique genes. NEUROG3 occupancy was found at promoters as well as at distant cis-regulatory elements that frequently overlapped within PEP active enhancers. De novo motif analyses defined a NEUROG3 consensus binding motif and suggested potential co-regulation of NEUROG3 target genes by FOXA or RFX transcription factors. We found that 22% of the genes downregulated in NEUROG3 Mapping NEUROG3 genome occupancy in PEPs uncovered unexpectedly broad, direct control of the endocrine genes, raising novel hypotheses on how this master regulator controls islet and beta cell differentiation. Show less