👤 Anna Andrianova

Intrinsic Capacity (IC) is defined as the composite of physical and mental abilities an individual possesses, encompassing five domains: cognition, psychological health, sensory function, vitality, and locomotion. This construct is central to the World Health Organization's framework for assessing functional ability in older adults. Growing evidence highlights the critical role of the musculoskeletal system in maintaining these domains, while conditions such as sarcopenia, osteoporosis, and their coexistence as osteosarcopenia (OS) are increasingly associated with IC decline. This narrative review compiles current evidence on the modulatory role of muscles and bones in IC and the impacts of sarcopenia, osteoporosis, and OS. Most findings suggest that musculoskeletal tissues influence IC not only through biomechanical functions but also as secretory organs, releasing myokines and osteokines with endocrine, paracrine, and autocrine effects. Among the most studied are brain-derived neurotrophic factor, irisin, osteocalcin, and interleukin-6. Dysregulation of these pathways, along with biomechanical dysfunction and systemic inflammation, links sarcopenia, osteoporosis, and OS to IC impairment. Further research is needed to clarify the specific mechanisms involved, particularly in the sensory and vitality domains, to inform targeted interventions that promote healthy aging. Show less

Leukocyte-platelet aggregates (LPAs) play a crucial role in the pathogenesis of inflammatory diseases, linking pathological immune responses with thrombosis.The levels of LPAs, their composition, and cellular reactivity were determined in patients with distinct inflammatory conditions, namely coronavirus disease 2019 (COVID-19), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE), compared with healthy controls. Flow cytometry was used to identify cell types and measure LPA levels in the blood. The ability of platelets, neutrophils, and monocytes to form additional LPAs in response to hyperstimulation with phorbol-12-myristate-13-acetate (PMA) was assessed. Coaggregation of isolated neutrophils and platelets in vitro was visualized using scanning electron microscopy. Blood tests included coagulation, hematology, biochemistry, and immunology.LPA levels were significantly higher in all patient groups compared with controls, with variations in the composition: neutrophil-platelet aggregates predominated in the COVID-19 patients, whereas monocyte-platelet aggregates prevailed in the blood of RA and SLE patients. Platelet-to-leukocyte ratios within aggregates varied in a broad range with a substantial prevalence of platelets over leukocytes. Morphological analysis revealed coaggregation of platelets with neutrophils, including relatively large homotypic platelet aggregates associated with one or two neutrophils. In PMA-treated pathological blood samples from COVID-19, RA, and SLE patients, the ability to form additional LPAs over the patients' baseline level was reduced compared with normal blood samples, indicating impaired reactivity (exhaustion) of neutrophils and monocytes in all patient groups.This study highlights distinct changes in the number and composition of LPAs in inflammatory diseases of various etiologies associated with altered functionality of the innate immune cells. Show less

Transcription factors LXRs, PPARs, and SREBPs have been implicated in a multitude of physiological and pathological processes including atherogenesis. However, little is known about the regulation of these transcription factors at different stages of atherosclerosis progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to compare the contents of mRNAs in pairs intact-injured aorta fragments taken from the same donors. Only minor changes in LXRα, LXRβ, PPARα, PPARγ, SREBP1, and SREBP2 mRNA levels were found in initial lesions as compared with intact non-diseased tissue. The contents of all mRNAs but SREBP2 mRNA were found to be progressively up-regulated in fatty streaks and fibrous lipoid plaques. These changes were only partially reproduced in cultured macrophages upon lipid loading. Wave-shaped changes in abundance of correlations between given group of mRNAs and 28 atherosclerosis-related mRNA species in the course of atherogenesis were observed. The impact of specific mRNA correlations on the total correlations also significantly varied between different lesion types. The study suggests that the extent and forms of LXR/PPAR/SREBP participation in intima functions vary nonlinear in individual fashion in atherogenesis. We speculate that the observed changes in mRNAs expression and coupling reflect shifts in lipid ligands availability and cellular composition in the course of atherosclerosis progression. Show less