Pharmacological Approaches Research Articles

9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2025.

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

Clinical Case Study on Osteoarthrosis: Integrative Treatment and Functional Improvement

Osteoarthrosis (OA) is a prevalent degenerative joint disease characterized by the progressive breakdown of articular cartilage and changes in subchondral bone, leading to pain, stiffness, and reduced joint function. Its management involves a combination of pharmacological and non-pharmacological approaches aimed at alleviating symptoms and improving quality of life.[1] Sandhivata is a term used in Ayurveda to describe a condition resembling osteoarthritis, characterized by joint pain, stiffness, and swelling. It is considered to be caused by an imbalance in the body's Doshas (humors), particularly Vata Dosha, leading to degeneration of the joints and surrounding tissues.[2] Routine full-body massage (Abhyanga) using warm, therapeutic oils aids in nourishing the tissues, improving circulation, and balancing Vata Dosha. Basti is a vital therapy for managing Vata-related conditions.

Activity-related dyspnea and exercise intolerance in chronic obstructive pulmonary disease: recent insights.

Exertional dyspnea and exercise intolerance remain key patient-related outcomes in chronic obstructive pulmonary disease (COPD). Improvement in treatment strategies is pendant further understand of their underpinnings across the spectrum of disease severity. Emerging literature has been reviewed based on a conceptual framework that relates ventilatory demand to capacity under the modulating influence of sub-cortical and cortical centers (symptom perception and affective interpretation). Evidence supporting these fundamental tenets is critically appraised, focusing on mechanistic and interventional studies that shed novel light on the sources of heightened and/or mechanically constrained ventilation. Mechanistic studies using proxies of the inspiratory neural drive (e.g., diaphragm electromyography) were particularly informative, as well as interventional trials aimed at decreasing afferent stimulation and/or symptom perception via pharmacological (e.g., low-dose opiates in selected patients, high flow oxygen, oral nitrate) and nonpharmacological (e.g., novel exercise training paradigms, inspiratory muscle training, breathing techniques) interventions. Therapeutic and rehabilitative strategies to lessen dyspnea's devastating impact on quality of life should minimize demand in the setting of reduced capacity and increased sensation awareness in COPD. The most successful attempts so far have amalgamated pharmacological and nonpharmacological approaches tailored to the main underlying mechanisms on an individual basis.

Brain region-specific neural activation by low-dose opioid promotes social behavior.

The opioid system plays crucial roles in modulating social behaviors in both humans and animals. However, the pharmacological profiles of opioids regarding social behavior and their therapeutic potential remain unclear. Multiple pharmacological, behavioral, and immunohistological c-Fos mapping approaches were used to characterize the effects of μ-opioid receptor agonists on social behavior and investigate the mechanisms in naive mice and autism spectrum disorder-like (ASD-like) mouse models, such as prenatally valproic acid-treated mice and Fmr1-KO mice. Here, we report that low-dose morphine, a μ-opioid receptor agonist, promoted social behavior by selectively activating neurons in prosocial brain regions, including the nucleus accumbens, but not those in the dorsomedial periaqueductal gray (dmPAG), which are only activated by analgesic high-dose morphine. Critically, intra-dmPAG morphine injection counteracted the prosocial effect of low-dose morphine, suggesting that dmPAG neural activation suppresses social behavior. Moreover, buprenorphine, a μ-opioid receptor partial agonist with less abuse liability and a well-established safety profile, ameliorated social behavior deficits in two mouse models recapitulating ASD symptoms by selectively activating prosocial brain regions without dmPAG neural activation. Our findings highlight the therapeutic potential of brain region-specific neural activation induced by low-dose opioids for social behavior deficits in ASD.

Homeostatic microglia initially seed and activated microglia later reshape amyloid plaques in Alzheimer’s Disease

The role of microglia in the amyloid cascade of Alzheimer’s disease (AD) is debated due to conflicting findings. Using a genetic and a pharmacological approach we demonstrate that depletion of microglia before amyloid-β (Aβ) plaque deposition, leads to a reduction in plaque numbers and neuritic dystrophy, confirming their role in plaque initiation. Transplanting human microglia restores Aβ plaque formation. While microglia depletion reduces insoluble Aβ levels, soluble Aβ concentrations stay consistent, challenging the view that microglia clear Aβ. In later stages, microglial depletion decreases plaque compaction and increases neuritic dystrophy, suggesting a protective role. Human microglia with the TREM2R47H/R47H mutation exacerbate plaque pathology, emphasizing the importance of non-reactive microglia in the initiation of the amyloid cascade. Adaptive immune depletion (Rag2-/-) does not affect microglia’s impact on plaque formation. These findings clarify conflicting reports, identifying microglia as key drivers of amyloid pathology, and raise questions about optimal therapeutic strategies for AD.

Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) drives abnormal pericyte-rich vasculature in triple-negative breast cancer.

Tumour angiogenesis supports malignant cells with oxygen and nutrients to promote invasion and metastasis. A number of cytokines released in situ participate in the recruitment of endothelial cells and pericytes to trigger the formation of novel blood vessels, which are often abnormal, leaky, and disorganized. Nicotinamide phosphoribosyltransferase is a key intracellular enzyme involved in NAD metabolism and is up regulated in many cancers to meet bioenergetic demands. Yet, the same protein is also secreted extracellularly (eNAMPT), where it acts as a pro-inflammatory cytokine. High plasma eNAMPT levels have been reported in breast cancer patients and correlate with aggressiveness and prognosis. We now report that in a triple-negative breast cancer model, enriching the tumour microenvironment with eNAMPT leads to abundant angiogenesis and increased metastatization. Atypically, the eNAMPT-mediated pro-angiogenic effect is mainly directed to NG2+ pericytes. Indeed, eNAMPT acts as chemoattractant for pericytes and coordinates vessel-like tube formation, in synergism with the classical factor PDGF-BB. Stimulation of pericytes by eNAMPT leads to a pro-inflammatory activation, characterized by the overexpression of key chemokines (CXCL8, CXCL1, CCL2) and VCAM1, via NF-κB signalling. All these effects were ablated by the use of C269, an anti-eNAMPT neutralizing antibody, suggesting that this might represent a novel anti-angiogenic pharmacological approach for triple-negative breast cancer.

N-methyl-D-aspartate receptor activation is downstream coupled to pannexin 1 opening by Src kinase in dorsal horn neurons: an essential link for mechanical hyperalgesia in nerve-injured rats.

A well-recognized molecular entity involved in pain-related neuroplasticity is the N-methyl-D-aspartate receptor (NMDAR), which is crucial for developing chronic pain. Likewise, the pannexin 1 (Panx1) channel has been described as necessary for initiating and maintaining neuropathic pain, driving nociceptive signals dependent on spinal NMDAR through several possible mechanisms. Through behavioral, pharmacological, and molecular approaches, our study in male rats has revealed several key findings: (1) neurons located in spinal cord laminae I and II express functional Panx1 channels in both neuropathic and sham rats. These channels can open (indicated by YOPRO-1 uptake) through the stimulation of NMDARs with intrathecal NMDA; (2) intrathecal NMDA leads to increased expression of pSrc and pPanx1 in dorsal horn neurons. This elevation exacerbates existing mechanical hyperalgesia in nerve-injured rats; (3) inhibition of Src with intrathecal PP2 or blockade of Panx1 with intrathecal 10Panx effectively mitigates NMDA-induced effects and reduces the spontaneous mechanical hyperalgesia of nerve-injured rats. Notably, while 10Panx successfully alleviates hyperalgesia, it does not alter pSrc expression; and (4) NMDA-stimulated YOPRO-1 uptake in neurons of laminae I-II of spinal cord slices were prevented by the NMDAR antagonist D-AP5, the Src inhibitor PP2 (but not PP3), as well as with the 10Panx and carbenoxolone. Therefore, NMDAR activation in dorsal horn neurons triggers an NMDAR-Src-Panx1 signaling pathway, where Panx1 acts as an enhancing effector in neuropathic pain. This implies that disrupting the NMDAR-Panx1 communication (eg, through Src inhibitors and/or Panx1 blockers) may offer a valuable strategy for managing some forms of chronic pain.

Pharmacological targeting of dopamine D1 or D2 receptors evokes a rapid-onset parkinsonian motor phenotype in mice.

Dopaminergic nigrostriatal denervation in Parkinson's disease (PD) disrupts the functional balance between striatal projecting neurons, leading to aberrant activity in the cortico-basal ganglia circuit and characteristic motor symptoms. While genetic and toxin-based animal models are commonly used to mimic PD pathology and behaviour, they have limitations when combined with circuit manipulation tools. This highlights the need for complementary approaches, particularly when combined with viral-based circuit targeting of specific neuronal subpopulations involved in PD circuit dysfunction. Here, we pursue a pharmacological approach targeting dopamine D1 or D2 receptors to induce dopamine deprivation and to replicate key motor symptoms in PD. We demonstrate a clear dose-dependent induction of parkinsonian motor behaviour by both a dopamine D1 receptor antagonist (SCH23390) and a D2 receptor antagonist (haloperidol). The motor phenotype is evaluated by considering relevant motor metrics in an open-field maze platform. The proposed parkinsonian pharmacological model constitutes an acute, flexible approach, which allows parallel brain circuit manipulations.

Methods of Managing Postoperative Pain in Orthopedics

Postoperative pain management is a critical concern for patients undergoing orthopedic procedures, impacting both recovery and overall patient satisfaction. Effective pain control is essential for minimizing complications such as limited mobility and delayed healing. This paper reviews contemporary strategies for managing postoperative pain in orthopedics, focusing on both pharmacological and non-pharmacological approaches. Pharmacotherapy, including nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, is commonly utilized but must be carefully managed to prevent adverse effects such as dependence and gastrointestinal issues. Complementing these methods, non-pharmacological interventions such as physical therapy, cryotherapy, transcutaneous nerve stimulation, and music therapy offer holistic benefits without the associated risks of medication. The study emphasizes the importance of a multifaceted approach that includes early rehabilitation and patient education to enhance recovery outcomes. The combined use of diverse pain management techniques can optimize analgesic efficacy while promoting patient comfort and reducing hospital stays, ultimately leading to improved rehabilitation results.

Definitive Evidence for the Identification and Function of Renin-Expressing Cholinergic Neurons in the Nucleus Ambiguus

BACKGROUND: The importance of the brain renin-angiotensin system in cardiovascular function is well accepted. However, not knowing the precise source of renin in the brain has been a limitation toward a complete understanding of how the brain renin-angiotensin system operates. METHODS: Highly sensitive in situ hybridization techniques and conditional knockout mice were used to address the location and function of renin in the brainstem. RESULTS: We identified novel renin-expressing cholinergic neurons in the nucleus ambiguus (NuAm), a major vagal cardioinhibitory center in the brainstem. The expression of renin-angiotensin system genes was relatively abundant in the NuAm, implying that angiotensin II might mediate an important regulatory role in this nucleus and other regions with neural connectivity to the NuAm. Then, we generated conditional knockout mice lacking the classical renin isoform (Ren-a ChAT-KO ), specifically in cholinergic neurons. Ablation of Ren-a in cholinergic neurons abrogated renin expression in the NuAm. Moreover, studies using radiotelemetry, heart rate variability analyses, and pharmacological approaches revealed that the parasympathetic nervous system is depressed in Ren-a ChAT-KO males while augmented in the Ren-a ChAT-KO females. Subsequently, transcriptomic approaches were used to infer putative genes and signaling pathways regulated by renin within the NuAm. CONCLUSIONS: This study revealed that renin in cholinergic neurons plays a fundamental role in preserving autonomic balance and cardiovascular homeostasis in a sex-dependent manner. These findings define the NuAm as an endogenous, local source of renin with biological function and serve as conclusive evidence for the presence and functionality of the brain renin-angiotensin system.

Emerging Pharmacological Approaches for Psychosis and Agitation in Alzheimer's Disease.

Psychosis and agitation are among the most distressing neuropsychiatric symptoms (NPSs) of Alzheimer's disease (AD), linked to faster disease progression and earlier admission to nursing homes. While nonpharmacological treatments may alleviate mild behavioral symptoms, more severe syndromes often require pharmacological intervention. Brexpiprazole is the only medication approved for agitation in AD, although its limited clinical efficacy has raised criticism. No drugs have been approved for treating psychosis in AD, highlighting the critical need for new, effective, and safe treatments. Recent studies have elucidated part of the neurobiological basis of NPSs in the AD brain, offering insights for testing repurposed and novel drugs. We conducted a comprehensive nonsystematic literature review, aiming to provide a critical overview of both current treatments and emerging pharmacological interventions under clinical development for treating psychosis and agitation in AD. Additionally, we present strategies to optimize the clinical development of new drug candidates. We identify three promising compounds that are currently in phase 3 trials: xanomeline-trospium for AD psychosis, and dextromethorphan-bupropion and dexmedetomidine for agitation in AD. We propose that biomarkers linked to the neuropsychiatric traits of AD patients should be identified in dedicated studies and then included in phase 2 dose-range-finding studies with novel compounds to establish biological engagement. Furthermore, phase 3 placebo-controlled studies should be carried out in AD biomarker-confirmed subjects with narrower cognitive impairment ranges and precise NPS severity at screening. Alternative study designs, such as sequential phase approaches, may also be adopted.

Novel Pharmacologic and Other Somatic Treatment Approaches for Posttraumatic Stress Disorder in Adults: State of the Evidence.

Posttraumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder that can become chronic and debilitating when left untreated. The most commonly recommended first-line treatments for PTSD among adults are individual trauma-focused psychotherapies. Other evidence-based treatments include specific antidepressant medications and non-trauma-focused psychotherapies. Despite the effectiveness of these available treatments, many patients' symptoms do not remit. This has led to the search for novel treatments for PTSD. In this review, the authors critically evaluate the data supporting several emerging pharmacological and other somatic interventions in the categories of medication-assisted psychotherapy, novel medication monotherapy strategies, and neuromodulation, selected because of the salience of their mechanisms of action to the pathophysiology of PTSD (e.g., MDMA-assisted psychotherapy, ketamine, cannabidiol, transcranial magnetic stimulation). The authors also evaluate the evidence for treatments that are the focus of increasing scientific or public interest (i.e., hyperbaric oxygen therapy, stellate ganglion block, neurofeedback). To date, the evidence supporting most novel pharmacological and somatic treatments for PTSD is preliminary and highly variable; however, the data for several specific treatments, such as transcranial magnetic stimulation, are encouraging.

Hydrogen gas enhances Arabidopsis salt tolerance by modulating hydrogen peroxide-mediated redox and ion homeostasis.

Hydrogen gas (H2) plays a crucial role in mitigating salt stress in plants, but the underlying mechanisms is largely unknown. Herein, we employed the pharmacological, molecular, and genetic approaches to investigate the positive roles of hydrogen peroxide (H2O2) in endogenous H2-induced salt tolerance of Arabidopsis thaliana. H2-induecd salt tolerance of CrHYD1 (hydrogenase 1 gene from Chlamydomonas reinhardtii) transgenic Arabidopsis was blocked by H2O2 scavenger or NADPH oxidase inhibitor. When RESPIRATORY BURST OXIDASE HOMOLOG (RBOH) genes (AtrbohD or AtrbohF) were mutated, salt sensitivity of CrHYD1/atrboh (especially CrHYD1/atrbohD) hybrids was increased, but diminished by exogenous H2O2 administration. Salt-stimulated endogenous H2 enrichment consequently resulted in the rapid reactive oxygen species (ROS) accumulation under early salt stress, and the expression of AtrbohD (especially) and AtrbohF in CrHYD1 plants was higher than those in the wild-type (WT), suggesting that endogenous H2 could induce Atrboh-dependent ROS burst to respond salt stress. Further, H2-induced less 3,3'-diaminobenzidine (DAB) and nitro blue tetrazolium (NBT) stain in CrHYD1 plants was reversed under salt stress when either H2O2 was removed or Atrbohs were mutated, which could be explained by higher H2O2 and thiobarbituric acid reactive substances (TBARS) levels, as well as lower antioxidant enzyme activity. Additionally, H2-induced Na+ discharge and K+ accumulation in CrHYD1 plants under salt stress were blocked by either H2O2 removal or Atrboh knockout, which was validated by higher Na+/K+ ratios and lower ion transport-related gene expression. Our findings not only elucidate that endogenous H2 enhanced Arabidopsis salt tolerance by reestablishing H2O2-dependent ion and redox homeostasis, but provide new insights into the mechanisms of plant salinity responses.

TGF-β receptor-specific NanoBRET Target Engagement in living cells for high-throughput kinase inhibitor screens

Targeting transforming growth factor-β (TGF-β) receptors is a promising pharmacological approach to normalize aberrant signaling in genetic and non-genetic TGF-β associated diseases including fibrosis, cancer, cardiovascular and musculoskeletal disorders. To identify novel TGF-β receptor kinase inhibitors, methods like in vitro kinase assays, western blot or transcriptional reporter assays are often used for screening purposes. While these methods may have certain advantages, the lack of integration of key features such as receptor specificity, high-throughput capability, and cellular context resemblance remains a major disadvantage. This deficiency could ultimately hinder the translation of study outcomes into later (clinical) stages of drug development. In this study, we introduce an adjusted and optimized live cell NanoBRET Target Engagement (TE)-based method to identify TGF-β receptor specific kinase inhibitors. This comprehensive toolkit contains various TGF-β type I and type II receptors, with corresponding nanoBRET tracers, and disease-related cell lines, including novel non-commercially available materials. The nanoBRET capacity and kinase inhibitory window can be significantly enhanced for functional measurements when stable expression cell lines and substantially low tracer concentrations are used. In addition, this system can be tailored to study TGF-β associated genetic disorders and possibly be used to screen for disease-specific therapeutics. Therefore, the use of this optimized, live cell, antibody-independent nanoBRET Target Engagement assay is highly encouraged for future high-throughput compound screens targeting TGF-β/BMP receptors.

Slow Metabolism-Driven Amplification of Hepatic PPARγ Agonism Mediates Benzbromarone-Induced Obesity-Specific Liver Injury.

Obesity and nonalcoholic fatty liver disease (NAFLD) are established risk factors for drug-induced liver injury (DILI). The previous study demonstrates that benzbromarone (BBR), a commonly prescribed pharmaceutical agent for managing gout and hyperuricemia, exacerbates hepatic steatosis and liver injury specifically in obese individuals. However, the precise mechanism underpinning this adverse effect remains incompletely elucidated. Given the significance of BBR and its analogs in anti-gout/hyperuricemia drug discovery, elucidating the mechanism by which BBR exacerbates obesity-specific DILI warrants further investigation. In this study, through a combined multi-omics, pharmacological, and pharmacokinetic approaches, it is found that BBR-induced obesity-specific DILI is primarily through the potentiation of peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathways. Further in vivo and in vitro pharmacokinetic analyses reveal that obese db/db mice exhibited a diminished capacity to metabolize BBR in their livers. This reduction leads to prolonged retention of BBR, subsequently resulting in chronic and sustained hepatic PPARγ agonism. This study demonstrates that a slow metabolism-driven amplification of hepatic PPARγ agonism mediates BBR-induced obesity-specific hepatic steatosis and subsequent DILI, which also emphasizes the importance of the reduced hepatic drug metabolism capacity in patients with obesity or pre-existing NAFLD in both clinical practice and drug discovery processes.

The dual GLP-1/glucagon receptor agonist G49 mimics bariatric surgery effects by inducing metabolic rewiring and inter-organ crosstalk

Bariatric surgery is effective for the treatment and remission of obesity and type 2 diabetes, but pharmacological approaches which exert similar metabolic adaptations are needed to avoid post-surgical complications. Here we show how G49, an oxyntomodulin (OXM) analog and dual glucagon/glucagon-like peptide-1 receptor (GCGR/GLP-1R) agonist, triggers an inter-organ crosstalk between adipose tissue, pancreas, and liver which is initiated by a rapid release of free fatty acids (FFAs) by white adipose tissue (WAT) in a GCGR-dependent manner. This interactome leads to elevations in adiponectin and fibroblast growth factor 21 (FGF21), causing WAT beiging, brown adipose tissue (BAT) activation, increased energy expenditure (EE) and weight loss. Elevation of OXM, under basal and postprandial conditions, and similar metabolic adaptations after G49 treatment were found in plasma from patients with obesity early after metabolic bariatric surgery. These results identify G49 as a potential pharmacological alternative sharing with bariatric surgery hormonal and metabolic pathways.

The IL-33/ST2 signaling axis drives pathogenesis in acute SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), remains a significant threat to global public health. Immunopathological damage plays a role in driving pneumonia, acute respiratory distress syndrome (ARDS), and multiorgan failure in severe COVID-19. Therefore, dissecting the pulmonary immune response to SARS-CoV-2 infection is critical to understand disease pathogenesis and identify immune pathways targetable by therapeutic intervention. Considering that the type 2 cytokine IL-13 enhances COVID-19 disease severity, therapeutic targeting of upstream signals that drive type 2 immunity may confer further protection. In this study, we investigate the role of the IL-33/ST2 signaling axis, a potent inducer of type 2 immunity in the lung, in a mouse model of COVID-19. Upon infection with mouse-adapted SARS-CoV-2 MA10, ST2 -/- mice had significantly improved weight loss and survival (69.2% vs 13.3% survival; P = 0.0005), as compared to wild-type mice. In a complementary pharmacologic approach, IL-33/ST2 signaling was inhibited using HpBARI_Hom2, a helminth derived protein that binds to mouse ST2 and blocks IL-33 signaling. In SARS-CoV-2 MA10 infection, HpBARI_Hom2-treated mice had significantly improved weight loss and survival (60% vs 10% survival; P = 0.0035), as compared to inert control-treated mice. These data demonstrate that loss of IL-33/ST2 signaling confers protection during acute SARS-CoV-2 MA10 infection, implicating the IL-33/ST2 signaling axis as an enhancer of COVID-19 disease severity. The protection conferred by pharmacologic blockade of IL-33/ST2 signaling was independent of viral control, as HpBARI_Hom2-treated mice had no reduction in viral titers. This finding suggests an immunopathogenic role for IL-33/ST2 signaling. One potential mechanism through which IL-33/ST2 signaling may drive severe disease is through enhancement of type 2 immune pathways including IL-5 production, as pulmonary IL-5 concentrations were found to depend on IL-33/ST2 signaling in acute SARS-CoV-2 MA10 infection.

Investigating the effect of verapamil on preservation of beta-cell function in adults with newly diagnosed type 1 diabetes mellitus (Ver-A-T1D): protocol for a randomised, double-blind, placebo-controlled, parallel-group, multicentre trial

IntroductionType 1 diabetes mellitus (T1DM) is a disorder that arises following the selective autoimmune destruction of the insulin-producing beta cells. Beta-cell protective or beta-cell regenerative approaches have gained wider attention,...

Mitochondrial Dysfunction in Atrial Fibrillation: The Need for a Strong Pharmacological Approach

Despite great progress in treating atrial fibrillation (AF), especially with the development of increasingly effective invasive techniques for AF ablation, many unanswered questions remain regarding the pathogenic mechanism of the arrhythmia and its prevention methods. The development of AF is based on anatomical and functional alterations in the cardiomyocyte resulting from altered ionic fluxes and cardiomyocyte electrophysiology. Electric instability and electrical remodeling underlying the arrhythmia may result from oxidative stress, also caused by possible mitochondrial dysfunction. The role of mitochondrial dysfunction in the pathogenesis of AF is not yet fully elucidated; however, the reduction in AF burden after therapeutic interventions that improve mitochondrial fitness tends to support this concept. This selected review aims to summarize the mechanisms of mitochondrial dysfunction related to AF and the current pharmacological treatment options that target mitochondria to prevent or improve the outcome of AF.

Possibilities of gene, cellular and pharmacological approaches to correct age-related changes

Improvement of the human habitat has led to an increase in average life expectancy. Long life goes hand in hand with old age, which reduces the quality of human life and it is an acute social problem. Thus, the search for approaches that can improve the quality of life, the ability to live it without age-related diseases is an extremely urgent task. Aging of the body begins with the aging of cells, in which the activation of the aging process occurs through the induction of specific signaling pathways, which irreversibly divides the life of any cell into “before and after”. Aging cells are able to influence their microenvironment, secreting more inflammatory signaling molecules and inducing pathological changes in neighboring cells. The accumulation and long-term preservation of aged cells lead to deterioration of the condition of tissues and organs, and ultimately to a decrease in the quality of life and an increased risk of death. Among the most promising approaches to the correction of aging and age-related diseases are pharmacological, gene and cell therapy. Increasing the expression of aging suppressor genes, using certain populations of native and genetically modified cells, as well as senolytic drugs can help delay aging and associated diseases for a more distant future. This review examines currently studied approaches and achievements in the field of anti-aging therapy, in particular gene therapy using adeno-associated vectors and approaches based on cell therapy.