Developmental and epileptic encephalopathies (DEEs) are a group of neuropediatric diseases associated with epileptic seizures, severe delay or regression of psychomotor development, and cognitive and behavioral deficits. What sets DEEs apart is their complex interplay of epilepsy and developmental delay, often driven by genetic factors. These two aspects influence one another but can develop independently, creating diagnostic and therapeutic challenges. Intellectual disability is severe and complicates potential treatment. Pathogenic variants are found in 30–50% of patients with DEE. Many genes mutated in DEEs encode ion channels, causing current conduction disruptions known as channelopathies. Although channelopathies indeed make up a significant proportion of DEE cases, many other mechanisms have been identified: impaired neurogenesis, metabolic disorders, disruption of dendrite and axon growth, maintenance and synapse formation abnormalities —synaptopathies. Here, we review recent publications on non-channelopathies in DEE with an emphasis on the mechanisms linking epileptiform activity with intellectual disability. We focus on three major mechanisms of intellectual disability in DEE and describe several recently identified genes involved in the pathogenesis of DEE.

Cognitive abilities decline with age, constituting a major manifestation of aging. The quantitative biomarkers of this process, as well as the correspondence to different biological clocks, remain largely an open problem. In this paper we employ the following cognitive tests: 1. differentiation of shades (campimetry); 2. evaluation of the arithmetic correctness and 3. detection of reversed letters and identify the most significant age-related cognitive indices. Based on their subsets we construct a machine learning-based Cognitive Clock that predicts chronological age with a mean absolute error of 8.62 years. Remarkably, epigenetic and phenotypic ages are predicted by Cognitive Clock with an even better accuracy. We also demonstrate the presence of correlations between cognitive, phenotypic and epigenetic age accelerations that suggests a deep connection between cognitive performance and aging status of an individual.

Nowadays, cardiovascular diseases (CVDs) occupy a leading position in population mortality. Since it is known that the development of cardiovascular pathologies is determined mainly by the human genetic burden, an urgent task of primary prevention of CVDs is to assess the contribution of gene polymorphism to the formation of cardiovascular risk. The material for the study was the blood of volunteers aged 21 to 102 years. Polymorphisms were determined by real–time PCR. Multichannel volumetric sphygmography was performed to analyze the functional state of the vascular wall. The study revealed that the rs5742904 polymorphism of the ApoB gene was found to be absent in the studied groups of long-livers and descendants of long-livers. Results indicated that the carriage of the heterozygous variant of the MMP9 polymorphism is associated with a favorable prognosis for cardiovascular system functioning. A tendency towards an increase in the rate of biological age acceleration among subgroups with AA and GG genotypes of the MMP9 gene and a negative value of biological age acceleration among heterozygous carriers of this polymorphism allele were found. The conducted studies make it possible to identify new associations of the studied polymorphisms with the functional state of the cardiovascular system, which is of great clinical importance and requires further study.

Sleep–wake cycle disorders most often accompany the elderly and are frequently associated with the development of neurodegenerative processes, primarily Alzheimer’s disease. Sleep disturbances can be diagnosed in patients with AD even before the onset of memory and cognitive impairment, and become more pronounced as the disease progresses. Therefore, the expansion of our knowledge of how sleep relates to AD pathogenesis needs to be addressed as soon as possible. Here, we investigated the influence of chronic sleep deprivation on the motor and orienting–exploratory activity of 5xFAD mice, as well as their spatial learning ability and long-term memory retention. The studies carried out revealed that chronic sleep deprivation negatively affects the processes of spatial memory reconsolidation in 5xFAD mice. This leads to the development of stress-related behavioral responses, including aggressive behavior. In addition, the morphological changes in the cerebral cortex, including changes in the nuclear–cytoplasmic ratio and degradation of neuronal processes are observed. Moreover, we found an increase in the level of total DNA methylation in the blood of the sleep-deprived mice, which may be one of the mechanisms of the two-way relationship between sleep and neurodegeneration.

Yakutia is one of the coldest permanently inhabited regions in the world, characterized by a subarctic climate with average January temperatures near −40 °C and the minimum below −60 °C. Recently, we demonstrated accelerated epigenetic aging of the Yakutian population in comparison to their Central Russian counterparts, residing in a considerably milder climate. In this paper, we analyzed these cohorts from the inflammaging perspective and addressed two hypotheses: a mismatch in the immunological profiles and accelerated inflammatory aging in Yakuts. We found that the levels of 17 cytokines displayed statistically significant differences in the mean values between the groups (with minimal p-value = 2.06 × 10⁻¹⁹), and 6 of them are among 10 SImAge markers. We demonstrated that five out of these six markers (PDGFB, CD40LG, VEGFA, PDGFA, and CXCL10) had higher mean levels in the Yakutian cohort, and therefore, due to their positive chronological age correlation, might indicate a trend toward accelerated inflammatory aging. At the same time, a statistically significant biological age acceleration difference between the two cohorts according to the inflammatory SImAge clock was not detected because they had similar levels of CXCL9, CCL22, and IL6, the top contributing biomarkers to SImAge. We introduced an explainable deep neural network to separate individual inflammatory profiles between the two groups, resulting in over 95% accuracy. The obtained results allow for hypothesizing the specificity of cytokine and chemokine profiles among people living in extremely cold climates, possibly reflecting the effects of long-term human (dis)adaptation to cold conditions related to inflammaging and the risk of developing a number of pathologies.