Age-related Chronic Diseases Research Articles

Emerging roles of frailty and inflammaging in risk assessment of age-related chronic diseases in older adults: the intersection between aging biology and personalized medicine

Emerging roles of frailty and inflammaging in risk assessment of age-related chronic diseases in older adults: the intersection between aging biology and personalized medicine

Plasma protein-based organ-specific aging and mortality models unveil diseases as accelerated aging of organismal systems.

Aging is a complex process manifesting at molecular, cellular, organ, and organismal levels. It leads to functional decline, disease, and ultimately death, but the relationship between these fundamental biomedical features remains elusive. By applying elastic net regularization to plasma proteome data of over 50,000 human subjects in the UK Biobank and other cohorts, we report interpretable organ-specific and conventional aging models trained on chronological age, mortality, and longitudinal proteome data. These models predict organ/system-specific disease and indicate that men age faster than women in most organs. Accelerated organ aging leads to diseases in these organs, and specific diets, lifestyles, professions, and medications influence organ aging rates. We then identify proteins driving these associations with organ-specific aging. Our analyses reveal that age-related chronic diseases epitomize accelerated organ- and system-specific aging, modifiable through environmental factors, advocating for both universal whole-organism and personalized organ/system-specific anti-aging interventions.

The role of high mobility group proteins in cellular senescence mechanisms.

Aging is a universal physiological phenomenon, and chronic age-related diseases have become one of the leading causes of human mortality, accounting for nearly half of all deaths. Studies have shown that reducing the incidence of these diseases can not only extend lifespan but also promote healthy aging. In recent years, the potential role of non-histone high-mobility group proteins (HMGs) in the regulation of aging and lifespan has attracted widespread attention. HMGs play critical roles in cellular senescence and associated diseases through various pathways, encompassing multi-layered mechanisms involving protein interactions, molecular regulation, and chromatin dynamics. This review provides a comprehensive analysis of the interactions between HMG family proteins and senescence-associated secretory phenotype (SASP), chromatin structure, and histone modifications, offering a deeper exploration of the pivotal functions and impacts of HMGs in the aging process. Furthermore, we summarize recent findings on the contributions of HMG proteins to aging and age-related diseases. HMG proteins not only regulate senescence-associated inflammation through modulating the SASP but also influence genomic stability and cell fate decisions via interactions with chromatin and histones. Targeting HMG proteins holds great potential in delaying the progression of aging and its associated diseases. This review aims to provide a systematic overview of HMG proteins' roles in aging and to lay a solid foundation for future anti-aging drug development and therapeutic strategies. With the advancing understanding of the mechanisms by which HMGs regulate aging, developing therapeutic interventions targeting HMGs may emerge as a promising approach to extending lifespan and enhancing healthspan.

Fisetin as a senotherapeutic agent: Evidence and perspectives for age-related diseases

Fisetin, a flavonoid naturally occurring in plants, fruits, and vegetables, has recently gained attention for its potential role as a senotherapeutic agent for the treatment of age-related chronic diseases. Senotherapeutics target senescent cells, which accumulate with age and disease, in both circulating immune cell populations and solid organs and tissues. Senescent cells contribute to development of many chronic diseases, primarily by eliciting systemic chronic inflammation through their senescence-associated secretory phenotype. Here, we explore whether fisetin as a senotherapeutic can eliminate senescent cells, and thereby alleviate chronic diseases, by examining current evidence from in vitro studies and animal models that investigate fisetin’s impact on age-related diseases, as well as from phase I/II trials in various patient populations. We discuss the application of fisetin in humans, including challenges and future directions. Our review of available data suggests that targeting senescent cells with fisetin offers a promising strategy for managing multiple chronic diseases, potentially transforming future healthcare for older and multimorbid patients. However, further studies are needed to establish the safety, pharmacokinetics, and efficacy of fisetin as a senotherapeutic, identify relevant and reliable outcome measures in human trials, optimize dosing, and better understand the possible limitations of fisetin as a senotherapeutic agent.

A reduced carbohydrate diet improves glycemic regulation in hyperglycemic older people in a retirement home: the SAGE study.

Poor glucose regulation associated with gradual insulin resistance is a significant risk factor in several age-related chronic diseases. An eating plan that promotes a lower carbohydrate intake may have a beneficial effect on glucose metabolism. This study aimed to evaluate how a diet reduced in carbohydrate by 32% (RCHO) over a 2 month period would influence the metabolic profile of older individuals (N=24) living in a retirement home (RH). A continuous glucose monitor was used to measure blood glucose during four periods: the standard diet before (baseline) and after (washout) the intervention, during the 4 initial days of the RCHO diet (RCHO-early), and the final days of the 2 month intervention (RCHO-end). The blood metabolic profile was also measured (glucose, ketones, insulin, triglycerides, and cholesterol). RCHO intake decreased average blood glucose compared to the standard diet in hyperglycemic participants: RCHO-early 7.8±1.0vs 7.5±1.1mM (p=0.012) and RCHO-end 7.8±1.0vs 7.0±0.9mM (p=0.050). In the hyperglycemic participants, the percentage of time spent in hyperglycemia (>10.0mM) decreased by 50% during the RCHO-early (p=0.012) and by 66% at RCHO-end (p =0.021) compared to baseline. Glycated hemoglobin was significantly lower at RCHO-end in both hyperglycemic and normoglycemic participants compared to baseline (p<0.008). Plasma ketones increased threefold in hyperglycemic participants at RCHO-end compared to baseline (p<0.028). This study shows that an RCHO diet has metabolic health benefits in an older population and confirms its safety, tolerability, and acceptability in an RH (NCT06022094).

A new model and precious tool to study molecular mechanisms of macrophage aging.

The accumulation of senescent cells, characterized by a senescence-associated secretory phenotype (SASP), contributes to chronic inflammation and age-related diseases (ARD). During aging, macrophages can adopt a senescent-like phenotype and an altered function, which promotes senescent cell accumulation. In the context of aging and ARD, controlling the resolution of the inflammatory response and preventing chronic inflammation, especially by targeting macrophages, must be a priority. Aging being a dynamic process, we developed a model of in vitro murine peritoneal macrophage aging. Our results show that macrophages cultured for 7 or 14 days exhibit a senescence-like phenotype: proliferation decrease, the levels of cyclin-dependent kinase inhibitors p16INK4A and p21CIP1 and of pro-inflammatory SASP components (MCP-1, IL-6, IL-1β, TNF-α, and MMP-9) increase, phagocytosis capacity decline and glycolytic activity is induced. In our model, chronic treatment with CB3, a thioredoxin-1 mimetic anti-inflammatory peptide, completely prevents p21CIP1 increase and enables day 14 macrophages to maintain proliferative activity.We describe a new model of macrophage aging with a senescence-like phenotype associated with inflammatory, metabolic and functional perturbations. This model is a valuable tool for characterizing macrophage aging mechanisms and developing innovative strategies with promising therapeutical purpose in limiting inflammaging and ARD.

Understanding dementia in minority ethnic communities: The perspectives of key stakeholders interviewed as part of the IDEAL programme.

Future populations of older adults in the UK, those aged 65+, will demonstrate increased diversity in terms of their ethnic identity resultant from the ageing of the post-war migrants from India, Pakistan, Bangladesh, and the Caribbean. As a consequence, there will be an increase in the numbers of older adults from these communities living with age-related chronic diseases such as dementia. In response to these demographic changes, we need to develop a research, policy and practice agenda that is inclusive and provides evidence for the development of culturally diverse and effective models of service delivery. This requires engagement with three key stakeholder groups: (a) people with dementia; (b) their carers; and (c) the wider community. As part of the IDEAL research programme on living well with dementia, we undertook semi-structured interviews with twelve community leaders, defined as known and trusted individuals active in their respective communities, and six community members (two people living with dementia and four carers). We explored their understandings, experiences, and views of about dementia. Our analysis identified two overarching themes. The migrant lifecourse highlighted issues of not belonging, discrimination and racism. This framed our second theme, the cultural context of dementia, which addressed dementia knowledge and attitudes, service provision and service access, and how being part of a minority ethnic community made a difference to these experiences. Our study highlights how lifecourse experiences of negative hostile social and policy environments and services can be profound and long-lasting and provide a prism through which accessing dementia care is experienced. Our findings argue for the inclusion of diverse views and lifecourse experiences within the context of developing a dementia strategy for research, policy and practice that is appropriate for a multicultural and heterogenous society.

A - 117 Double Trouble: a Case Study on Cardiac Amyloidosis and Alzheimer’s Disease

Abstract Objective Transthyretin amyloidosis (ATTR) is an increasingly recognized cause of heart failure amongst older adults. The median age upon diagnosis is 75 with 90% of patients reported as men. The amyloidogenic protein is transthyretin (TTR), which is primarily produced in the liver, but is also produced in the choroid plexus and neurons under distress. There are two types of ATTR: an autosomal dominant and a wild-type (wt) variant. ATTRwt is the amyloid precursor in the cardiac depositions found in older adults. We present the first neuropsychological evaluation of a patient with ATTRwt. Method An 87-year-old right-handed White woman reported a 2 year history of slowly progressive short term memory decline. Her family noted rapid cognitive decline and paranoia approximately 6 months ago. Medical history was notable for heart failure, along with lumbar stenosis, carpal tunnel syndrome, arthritis, scoliosis, and hyperlipidemia. ATTRwt diagnosis was made during cardiac clearance for lumbar surgery. Neuroimaging documented age-related cerebral atrophy and chronic microvascular ischemic disease. Results Inspection of data revealed an amnestic presentation, with impaired confrontational naming, spatial judgment, and processing speed performances. She denied depressogenic and anxiolytic symptoms while family endorsed symptoms of apathy and executive dysfunction. Conclusions The relationship between cardiac and nervous systems has garnished increasing attention in the literature and in clinical planning. Overall, the relationship between cardiac TTR amyloid and brain amyloid beta deposition in humans is unclear. Neuropsychologists should be aware of this heart condition that is increasingly recognized in older adults and the intriguing findings implicated around the cardiac-brain axis.

Aged bone marrow macrophages drive systemic aging and age-related dysfunction via extracellular vesicle-mediated induction of paracrine senescence.

The accumulation and systemic propagation of senescent cells contributes to physiological aging and age-related pathology. However, which cell types are most susceptible to the aged milieu and could be responsible for the propagation of senescence has remained unclear. Here we found that physiologically aged bone marrow monocytes/macrophages (BMMs) propagate senescence to multiple tissues, through extracellular vesicles (EVs), and drive age-associated dysfunction in mice. We identified peroxisome proliferator-activated receptor α (PPARα) as a target of microRNAs within aged BMM-EVs that regulates downstream effects on senescence and age-related dysfunction. Demonstrating therapeutic potential, we report that treatment with the PPARα agonist fenofibrate effectively restores tissue homeostasis in aged mice. Suggesting conservation to humans, in a cohort study of 7,986 participants, we found that fenofibrate use is associated with a reduced risk of age-related chronic disease and higher life expectancy. Together, our findings establish that BMMs can propagate senescence to distant tissues and cause age-related dysfunction, and they provide supportive evidence for fenofibrate to extend healthy lifespan.

Role of Phytochemicals in Treatment of Aging and Cancer: Focus on Mechanism of FOXO3 Activation.

There have been many studies reporting that the regular consumption of fruits and vegetables is associated with reduced risks of cancer and age-related chronic diseases. Recent studies have demonstrated that reducing reactive oxygen species and inflammation by phytochemicals derived from natural sources can extend lifespans in a range of model organisms. Phytochemicals derived from fruits and vegetables have been known to display both preventative and suppressive activities against various types of cancer via in vitro and in vivo research by interfering with cellular processes critical for tumor development. The current challenge lies in creating tailored supplements containing specific phytochemicals for individual needs. Achieving this goal requires a deeper understanding of the molecular mechanisms through which phytochemicals affect human health. In this review, we examine recently (from 2010 to 2024) reported plant extracts and phytochemicals with established anti-aging and anti-cancer effects via the activation of FOXO3 transcriptional factor. Additionally, we provide an overview of the cellular and molecular mechanisms by which these molecules exert their anti-aging and anti-cancer effects in specific model systems. Lastly, we discuss the limitations of the current research approach and outline for potential future directions in this field.

Inflammaging, Epigenetic Damage, Mitochondrial Dysfunctions, and Macrophage Alterations are the Main Missing Pieces in the Complex Mosaic of Stem Cell Physiology.

Aging is frequently associated with a progressive increase in chronic low-grade inflammation, known as "inflammaging". Numerous studies have shown that inflammaging is closely linked to the development of several age-related diseases. However, the underlying mechanism and its causal role are still not fully understood despite this association. In the complex context of aging, mesenchymal stem cells (MSCs) undergo changes in behavior and functionality. This narrative topical review examines the recent advances in aging research, specifically focusing on the role of inflammaging and related mechanisms that contribute to age-related chronic diseases. The authors critically investigated whether and how inflammaging, epigenetic damage, mitochondrial changes, and macrophage alterations may influence stem cell behavior, highlighting the interplay between these factors and their potential therapeutic implications. By elucidating the mechanisms underlying these processes, we can gain valuable insights into the maintenance and regeneration of stem cell populations, providing the basis for novel therapeutic strategies targeting age-related decline and disease progression.

Ferroptosis-A Shared Mechanism for Parkinson's Disease and Type 2 Diabetes.

Type 2 diabetes (T2D) and Parkinson's disease (PD) are the two most frequent age-related chronic diseases. There are many similarities between the two diseases: both are chronic diseases; both are the result of a decrease in a specific substance-insulin in T2D and dopamine in PD; and both are caused by the destruction of specific cells-beta pancreatic cells in T2D and dopaminergic neurons in PD. Recent epidemiological and experimental studies have found that there are common underlying mechanisms in the pathophysiology of T2D and PD: chronic inflammation, mitochondrial dysfunction, impaired protein handling and ferroptosis. Epidemiological research has indicated that there is a higher risk of PD in individuals with T2D. Moreover, clinical studies have observed that the symptoms of Parkinson's disease worsen significantly after the onset of T2D. This article provides an up-to-date review on the intricate interplay between oxidative stress, reactive oxygen species (ROS) and ferroptosis in PD and T2D. By understanding the shared molecular pathways and how they can be modulated, we can develop more effective therapies, or we can repurpose existing drugs to improve patient outcomes in both disorders.

The Antioxidant and Anti-Inflammatory Properties of Bee Pollen from Acorn (Quercus acutissima Carr.) and Darae (Actinidia arguta).

Aging is a complex biological process characterized by a progressive decline in physical function and an increased risk of age-related chronic diseases. Additionally, oxidative stress is known to cause severe tissue damage and inflammation. Pollens from acorn and darae are extensively produced in Korea. However, the underlying molecular mechanisms of these components under the conditions of inflammation and oxidative stress remain largely unknown. This study aimed to investigate the effect of bee pollen components on lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophages. This study demonstrates that acorn and darae significantly inhibit the LPS-induced production of inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), in RAW 264.7 cells. Specifically, bee pollen from acorn reduces NO production by 69.23 ± 0.04% and PGE2 production by 44.16 ± 0.08%, while bee pollen from darae decreases NO production by 78.21 ± 0.06% and PGE2 production by 66.23 ± 0.1%. Furthermore, bee pollen from acorn and darae reduced active oxygen species (ROS) production by 47.01 ± 0.5% and 60 ± 0.9%, respectively. It increased the nuclear potential of nuclear factor erythroid 2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 cells. Moreover, treatment with acorn and darae abolished the nuclear potential of nuclear factor κB (NF-κB) and reduced the expression of extracellular signal-associated kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation in LPS-stimulated RAW 264.7 cells. Specifically, acorn decreased NF-κB nuclear potential by 90.01 ± 0.3%, ERK phosphorylation by 76.19 ± 1.1%, and JNK phosphorylation by 57.14 ± 1.2%. Similarly, darae reduced NF-κB nuclear potential by 92.21 ± 0.5%, ERK phosphorylation by 61.11 ± 0.8%, and JNK phosphorylation by 59.72 ± 1.12%. These results suggest that acorn and darae could be potential antioxidants and anti-inflammatory agents.

Assessing the Effectiveness of eHealth Interventions to Manage Multiple Lifestyle Risk Behaviors Among Older Adults: Systematic Review and Meta-Analysis.

Developing adverse lifestyle behaviors increases the risk of a variety of chronic age-related diseases, including cardiovascular disease, obesity, and Alzheimer disease. There is limited evidence regarding the effectiveness of eHealth-based multiple health behavior change (MHBC) interventions to manage lifestyle risk behaviors. The purpose of this systematic evaluation was to assess the effectiveness of eHealth MHBC interventions in changing ≥2 major lifestyle risk behaviors in people aged ≥50 years. The literature search was conducted in 6 electronic databases-PubMed, Embase, Web of Science, Scopus, Cochrane Library, and SPORTDiscus-from inception to May 1, 2024. Eligible studies were randomized controlled trials of eHealth interventions targeting ≥2 of 6 behaviors of interest: alcohol use, smoking, diet, physical activity (PA), sedentary behavior, and sleep. A total of 34 articles with 35 studies were included. eHealth-based MHBC interventions significantly increased smoking cessation rates (odds ratio 2.09, 95% CI 1.62-2.70; P<.001), fruit intake (standardized mean difference [SMD] 0.18, 95% CI 0.04-0.32; P=.01), vegetable intake (SMD 0.17, 95% CI 0.05-0.28; P=.003), self-reported total PA (SMD 0.22, 95% CI 0.02-0.43; P=.03), and objectively measured moderate to vigorous PA (SMD 0.25, 95% CI 0.09-0.41; P=.002); in addition, the interventions decreased fat intake (SMD -0.23, 95% CI -0.33 to -0.13; P<.001). No effects were observed for alcohol use, sedentary behavior, or sleep. A sensitivity analysis was conducted to test the robustness of the pooled results. Moreover, the certainty of evidence was evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. eHealth-based MHBC interventions may be a promising strategy to increase PA, improve diet, and reduce smoking among older adults. However, the effect sizes were small. Further high-quality, older adult-oriented research is needed to develop eHealth interventions that can change multiple behaviors. PROSPERO International Prospective Register of Systematic Reviews CRD42023444418; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023444418.

Phytoene and Phytoene-Rich Microalgae Extracts Extend Lifespan in C. elegans and Protect against Amyloid-β Toxicity in an Alzheimer's Disease Model.

Phytoene is a colourless carotenoid widely available from dietary sources and a precursor for the synthesis of other carotenoids. Although present at high concentrations across different tissues, phytoene is largely viewed as not having physiological activity. Here, we utilize the model organism C. elegans to show that phytoene is bioactive and has anti-ageing properties. Supplementation with phytoene protects against oxidative damage and amyloid-β42 proteotoxicity (a major pathology of Alzheimer's disease), and extends lifespan. We also examine extracts from two microalgae, Chlorella sorokiniana and Dunaliella bardawil. We show that the extracts contain high levels of phytoene, and find that these phytoene-rich extracts have protective effects similar to pure phytoene. Our findings show that phytoene is a bioactive molecule with positive effects on ageing and longevity. Our work also suggests that phytoene-rich microalgae extracts can utilized to produce foods or supplements that promote healthy ageing and prevent the development of chronic age-related diseases.

Increasing age and lethal opiate use.

Opioid abuse is a leading cause of drug-related morbidity and mortality worldwide. It has been suggested that the age of opiate users in Australia is rising. To evaluate this further in a local population, toxicology and pathology case files from Forensic Science SA, Adelaide, South Australia, were examined for all cases with lethal opioid levels from 2000 to 2019 (n = 499; M:F 2.3:1; age range 18-91 years, median age 42 years). The median age of opiate deaths increased significantly by approximately 16 years (p = 0.007, R2 = 0.34) with a significant increase in total deaths in the 45-54 years and 55-64 years age groups (p = 0.009, R2 = 0.32) (p = < 0.001, R2 = 0.54). Deaths due to heroin overdose showed the lowest median age (39 years, n = 184), with deaths from tramadol toxicity having the highest (50.5 years, n = 32). Recent changes in the demographic profile of opioid users in cases of lethal overdose involve an aging population. Forensic and clinical practitioners should be aware of significant opioid abuse in certain individuals at older ages as this raises the possibility that this may exacerbate the effects of age-related chronic diseases in this group and/or contribute to fatalities.

Risk for hypertension and heart failure linked to high normal serum sodium and tonicity in electronic medical records.

Population aging is fueling an epidemic of age-related chronic diseases. Managing risk factors and lifestyle interventions have proven effective in disease prevention. Epidemiological studies have linked markers of poor hydration with higher risk of chronic diseases and premature mortality. Many individuals do not adhere to recommended hydration levels and could benefit from improved hydration habits. Our study evaluates the use of electronic medical records to confirm the relationship between inadequate hydration and the risk of chronic diseases, which may inform hydration-focused interventions in general healthcare. We analyzed 20-year electronic medical records for 411,029 adults from Israel's Leumit Healthcare Services. Hydration status was assessed using serum sodium and tonicity. We included adults without significant chronic diseases or water balance issues, defined as having normal serum sodium (135-146 mmol/l) and no diagnosis of diabetes. We used Cox proportional hazards models, adjusted for age, to assess the risk of developing hypertension and heart failure. Our findings showed an increased risk of hypertension with elevated serum sodium levels: a 12% rise for the 140-142 mmol/l group and 30% for levels above 143 mmol/l (HR1.30, 95%CI:1.26-1.34). Tonicity over 287 mosmol/kg was associated with a 19% increased risk of hypertension (HR1.19, 95%CI:1.17-1.22). The risk of heart failure also increased, reaching 20% for sodium levels above 143 mmol/l (HR1.20,95%CI:1.12-1.29) and 16% for tonicity above 289 mosmol/kg (HR1.16, 95%CI: 1.10-1.22). The association between sodium and hypertension was observed across genders, while the risk of heart failure was more pronounced in females. Within the healthy Leumit cohort, 19% had serum sodium levels within the 143-146 mmol/l range, and 39% were in the 140-142 mmol/l range. Data analysis from electronic medical records identified a link between serum sodium of 140 mmol/l and above and increased risk of hypertension and heart failure in the general Israeli population. Identifying individuals with high-normal sodium values in healthcare records could guide improvements in hydration habits, potentially leading to better health outcomes.

SCARF2 is a target for chronic obstructive pulmonary disease: Evidence from multi-omics research and cohort validation.

Age-related chronic inflammatory lung diseases impose a threat on public health, including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). However, their etiology and potential targets have not been clarified. We performed genome-wide meta-analysis for IPF with the largest sample size (2883 cases and 741,929 controls) and leveraged the summary statistics of COPD (17,547 cases and 617,598 controls). Transcriptome-wide and proteome-wide Mendelian randomization (MR) designs, together with genetic colocalization, were implemented to find robust targets. The mediation effect was assessed using leukocyte telomere length (LTL). The single-cell transcriptome analysis was performed to link targets with cell types. Individual-level data from UK Biobank (UKB) were used to validate our findings. Sixteen genetically predicted plasma proteins were causally associated with the risk of IPF and 6 proteins were causally associated with COPD. Therein, genetically-elevated plasma level of SCARF2 protein should reduce the risk of both IPF (odds ratio, OR = 0.9974 [0.9970, 0.9978]) and COPD (OR = 0.7431 [0.6253, 0.8831]) and such effects were not mediated by LTL. Genetic colocalization further corroborated these MR results of SCARF2. The transcriptome-wide MR confirmed that higher expression level of SCARF2 was associated with a reduced risk of both. However, the single-cell RNA analysis indicated that SCARF2 expression level was only relatively lower in epithelial cells of COPD lung tissue compared to normal lung tissue. UKB data implicated an inverse association of serum SCARF2 protein with COPD (hazard ratio, HR = 1.215 [1.106, 1.335]). The SCARF2 gene should be a novel target for COP.

Cytokines assets in PLWH in two-drug dolutergravir based or three-drug antiretroviral regimen

To minimize the toxicity and impact of combined antiretroviral therapy (cART) on the lifestyle of people living with Human Immunodeficiency Virus (PLWH), scientific community evaluated the efficacy, safety and sustained virologic response of two drugs antiretroviral regimens, in particular dolutegravir (DTG). The effects of deintensification therapy on inflammatory settings are currently unknown in PLWH. Thus, our study explored the inflammatory state in virologically suppressed HIV individuals between patients in treatment with a DTG-containing dual therapy (2DR) versus triple regimen therapies (3DR). We enrolled a total of 116 subjects in 2DRs or 3DRs regimens, and the plasma levels of pro- and anti-inflammatory cytokines (in particular IL-1β, IL-10, IL-18, IL-33, IL-36 and IFN-γ) have been evaluated. CD4 + cell’s median value was 729.0 cell/µL in the 3DR group and 771.5 cell/µL in 2DR group; the viral load was negative in all patients. Significant differences were found in levels of IL-18 (648.8 cell/µL in 3DR group vs. 475.0 cell/µL in 2DR group, p = 0.034) and IL-36 (281.7 cell/µL in 3DR group vs. 247.0 cell/µL in 2DR group, p = 0.050), and a correlation between IL-18 and IL-36 was found in 3DR group (rho = 0.266, p = 0.015). This single-center retrospective pharmacological study confirms the absence of significant differences in IL-1β, IL-10, IL-33, and IFN-γ levels between patients on two-drug antiretroviral regimens compared to patients on 3DR antiretroviral regimens. Patients in 2DR show greater control over IL-18 and IL-36 serum levels, cytokines related to an increased cardiovascular risk and development of age-related chronic diseases. Based on our results, we suggest that DTG-based 2DR antiretroviral regimens could be associated with better control of the chronic inflammation that characterizes the population living with HIV in effective ART.

SAFETY ASSESSMENT OF A RANGE OF PLANT METABOLIC TOVES – ADVANCED GEROPROTECTORS IN VIVO RESEARCH

Background. Ageing is associated with progressive impairment of physical functions and increased risk of age-related chronic diseases. Polyphenols such as mangiferin, quercetin and trans-cinnamic acid are also used for the treatment and prevention of chronic diseases. Toxicological research was important in biomedical research, as some high-dose extracted polyphenols could contribute to the development and progression of cancer and other diseases. This study is aimed at assessing toxicological safety of previously isolated phenolic compounds from plants of the Siberian Federal District. Materials and methods. Rodents have been chosen as the model organism. The study of mutagenic and antimutagenic properties was carried out using a micronuclear test of bone marrow cell. Cytotoxicity in vitro was assessed using the MTT test. Results. Polyphenols studied at doses of 50.0 and 100.0 mg/kg are not mutagenic. Mangiferri and quercetin at a dose of 50.0 mg/kg do not have anti-thagenic effects. In this case, trans-cinnamic acid in the same concentration has antimutagenic effect. Mangiferin in concentrates from 4.2 to 16.7 ug/ml has a cytotoxic effect. Trans-cinnamic acid is not cytotoxic (at 2.1-33.3 ug/ml). Quercetin has a cytotoxic effect in concentrations of 0.21 and 1.67 ug/ml, and at concentrations of 3.33 ug/ml increases the viability of splenocytes, presumably due to antioxidant properties. Conclusion. Safety or low toxicity is a decisive advantage of the continued use of polyphenols as advanced heroic flow agents. Further study of biologically active substances (mangiferin, quercetin and trans-cinnamic acid) has been found to be ce-woody. The work was carried out by the state task on the topic «Development of biologically active additives consisting of metabolites of plant objects in vitro to protect the population from premature aging» (project FZSR-2024-0008) using the equipment of Center of Collective Use «Instrumental methods of analysis in the field of applied biotechnology» on the basis of KemSU.