Kristina Shpiliukova

N6-methyladenosine (m⁶A) modifications are among the most prevalent epigenetic marks in eukaryotic RNAs, regulating both coding and non-coding RNAs and playing a pivotal role in RNA metabolism. Given their widespread influence, m⁶A modifications are deeply implicated in the pathogenesis of various cancers, including highly aggressive malignancies such as lung cancer, melanoma, and liver cancer. Dysregulation of m⁶A dynamics—marked by an imbalance in methylation and demethylation—can drive tumor progression, enhance metastatic potential, increase aggressiveness, and promote drug resistance, while also exerting context-dependent tumor-suppressive effects. Given this dual role, precise modulation of m⁶A levels and the activity of its regulatory enzymes (writers, erasers, and readers) represent a promising therapeutic avenue. In this review, we highlight recent advances in targeting m⁶A machinery, including small-molecule inhibitors, antisense oligonucleotides, and CRISPR/Cas-based editing tools, capable of both writing and erasing m⁶A marks and altering m⁶A methylation sites per se. By evaluating these strategies, we aim to identify the most effective approaches for restoring physiological m⁶A homeostasis or for strategically manipulating the m⁶A machinery for therapeutic benefit.

Aging is accompanied by a significant increase in the number of age-associated diseases, which has a serious impact on the individual and society. Against the background of a steady increase in the number of elderly people, the concept of frailty is now actively used in medicine. It implies increased vulnerability to various health problems associated with a decrease in physiological reserves against the background of aging, including accelerated aging in neurodegeneration. Psychosocial, environmental and age-related biological factors contribute to the decline in physical and cognitive abilities. Their culmination leads to the condition known as physical frailty, in addition to which a lot of researchers are emphasizing the phenomenon of cognitive frailty as a manifestation of cognitive impairment on the background of increasing physical weakness. The review presents an up-to-date analysis of the literature on frailty as a multidimensional and dynamic process, focusing on the role of cognitive reserve in aging. Evidence from cross-sectional and longitudinal studies is reviewed, showing that cognitive frailty is associated with increased risk of disability, impaired quality of life, hospitalizations, mortality, and neurocognitive disorders. This emphasizes the importance of introducing this concept into the clinical practice of geriatricians and neurologists. The article reviews data on the epidemiology, diagnostic approaches used, and perspectives.

The article examines the relationship between social fragility and cognitive impairment (CI) in elderly in the context of population ageing and the increasing proportion of age-related diseases. Social fragility is defined as a progressive loss of social resources, including support and social engagement, which is associated with an increased risk of depression, cognitive decline and dementia.A comprehensive review of studies published between 2017, and November 2024 was conducted to examine social fragility and its association with CI. The paper provides an overview of current approaches to assessing social fragility, including the use of indices and scales. The main risk factors, including depression, physical activity and CI, and the mechanisms underlying this relationship are analyzed in detail.Particular attention is paid to the consequences of social fragility for cognitive health and possible prevention strategies. The article discusses the role of social isolation, loneliness, reduced physical activity and diminished social interactions as key aspects that increase the risk of cognitive decline. It also points out that maintaining an active social network and participating in social life can slow the progression of CI and improve the quality of life of elderly.Our work emphasizes the need for an interdisciplinary approach to the diagnosis and treatment of social fragility, which includes the development of social relationships, the promotion of physical activity and the participation in group activities. These measures can help to strengthen cognitive reserves, reduce the negative effects of social fragility and ensure an active, long life for the elderly population.