The term resilience, which has been present in science for almost half a century, stands for the capacity of some system needed to overcome an amount of disturbance from the environment in order to avoid a change to another stable state. In medicine, the concept of resilience means the ability to deal with daily stress and disturbance to our homeostasis with the intention of protecting it from disturbance. With aging, the organism becomes more sensitive to environmental impacts and more susceptible to changes. Mental disturbances and a decline in psychological resilience in older people are potentiated with many social and environmental factors along with a subjective perception of decreasing health. Distinct from findings in younger age groups, mental and physical medical conditions in older people are closely associated with each other, sharing common mechanisms and potentiating each other’s development. Increased inflammation and oxidative stress have been recognized as the main driving mechanisms in the development of aging diseases. This paper aims to reveal, through a translational approach, physiological and molecular mechanisms of emotional distress and low psychological resilience in older individuals as driving mechanisms for the accelerated development of chronic aging diseases, and to systematize the available information sources on strategies for mitigation of low resilience in order to prevent chronic diseases.

Given that the increase in the aging population has grown into one of the largest public health issues, inflammation and oxidative stress, which are closely associated with the aging process, became a focus of recent research. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, a group of drugs initially developed as oral antidiabetics, have shown many beneficial effects over time, including improvement in renal function and cardioprotective effects. It has been shown that SGLT2 inhibitors, as a drug class, have an immunomodulatory and antioxidative effect, affecting endothelial function as well as metabolic parameters. Therefore, it is not surprising that various studies have investigated the potential mechanisms of action of SGLT2 inhibitors in age-related diseases. The proposed mechanisms by which SGLT2 inhibitors can achieve their anti-inflammatory effects include influence on AMPK/SIRT1/PGC-1α signaling, various cytokines, and the NLRP3 inflammasome. The antioxidative effect is related to their action on mitochondria and their influence on the signaling pathways of transforming growth factor β and nuclear erythroid 2-related factor 2/antioxidant response element. Also, SGLT2 inhibitors achieve their anti-inflammatory and antioxidative effects by affecting metabolic parameters, such as uric acid reduction, stimulation of ketogenesis, reduction of body weight, lipolysis, and epicardial fat tissue. Finally, SGLT2 inhibitors display anti-atherosclerotic effects that modulate inflammatory reactions, potentially resulting in improvement in endothelial function. This narrative review offers a complete and comprehensive overview of the possible pathophysiologic mechanisms of the SGLT2 inhibitors involved in the aging process and development of age-related disease. However, in order to use SGLT2 inhibitor drugs as an anti-aging therapy, further basic and clinical research is needed to elucidate the potential effects and complex mechanisms they have on inflammation processes.

Background: Aging is associated with many personal, social, and environmental challenges that increase the risk of loneliness. Loneliness is a painful emotional experience associated with a perceived lack of connection and intimacy. Loneliness accelerates health deterioration, but the presence of chronic health conditions (comorbidities) in older individuals may potentiate the feeling of loneliness. The relationships between health status and loneliness in older individuals have not been assessed in an integrated manner, although it is necessary for planning efficient interventions. The aim of this study was to fill in this knowledge gap, by attempting to create an integrated model of loneliness in older individuals. Methods: The sample consisted of 189 (58% F) older individuals (> 60 years) (mean ± SD, 78.47 ± 6.65), attendees in Primary Health Care. Different factors associated with loneliness in the older population were assessed, and classified as demographic, environmental, physical (health-related), and psychological, in addition to functional abilities. A set of standard questionnaires was used to assess psychological factors and functional abilities. The hierarchical regression model assessed the effect of particular blocks of factors on status loneliness. The second aim was to analyze how psychological factors mediate associations between health status (comorbidity level) and loneliness. Results: Indicated that increasing comorbidity, anxiety, lack of positive moods, not having hobbies/activities, low perception of social support, impaired cognitive function, and suppression of emotion expression, are significant predictors of loneliness. Mediation analysis informed us of how to help patients with comorbidities feel less lonely. Interventions that were suggested were those that can reduce anxiety and depression, improve cognitive abilities and emotional regulation control, and enhance social support. Conclusions: Results can help understand the pathophysiology loops linking poor health status (comorbidity level) of older individuals and loneliness, and have significant potentials from the translational perspectives, as a decision-support tool.

Chronic diseases, such as type 2 diabetes (T2D), are difficult to manage because they demand continuous therapeutic review and monitoring. Beyond achieving the target HbA1c, new guidelines for the therapy of T2D have been introduced with the new groups of antidiabetics, glucagon-like peptide-1 receptor agonists (GLP-1ra) and sodium-glucose cotransporter-2 inhibitors (SGLT2-in). Despite new guidelines, clinical inertia, which can be caused by physicians, patients or the healthcare system, results in T2D not being effectively managed. This opinion paper explores the shift in T2D treatment, challenging assumptions and evidence-based recommendations, particularly for family physicians, considering the patient’s overall situation in decision-making. We looked for the possible reasons for clinical inertia and the poor application of guidelines in the management of T2D. Guidelines for antidiabetic drugs should be more precise, providing case studies and clinical examples to define clinical contexts and contraindications. Knowledge communication can improve confidence and should include clear statements on areas of decision-making not supported by evidence. Precision medicine initiatives in diabetes aim to identify subcategories of T2D patients (including frail patients) using clustering techniques from data science applications, focusing on CV and poor treatment outcomes. Clear, unconditional recommendations for personalized T2D management may encourage drug prescription, especially for family physicians dealing with diverse patient contexts and clinical settings.

The treatment approaches of type 2 diabetes (T2D) are being transformed, due to the availability of novel antidiabetic medications, sodium-glucose co-transporter 2 inhibitors (SGLT2ins), and glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Despite their proven beneficial effects, recent research points to their insufficient prescription. This study aimed to reveal the prescription rates of SGLT2ins and GLP-1 RAs among general practitioners (GPs) in Croatia and to examine factors associated with their low self-confidence in prescribing them. A self-designed survey questionnaire was used and delivered to the GPs’ e-mail addresses in digital format. The data on the number of individuals diagnosed with T2D and prescribed new antidiabetic medications were checked by the respondents in their electronic database. Factors associated with lower GPs` self-confidence in prescribing SGLT2ins and GLP-1 RAs were assessed by bivariate and multivariate logistic regression analyses. The study included 168 GPs (66.1% women; 49.4% specialists in family medicine) and a cohort of 23,036 individuals with T2D. The prescription rates of SGLT2ins and GLP-1 RAs were 21.0% and 14.4%, respectively. Specialists stated a higher level of self-confidence in prescribing these medications, compared to other respondents. In the multivariate models, a factor that was shown to reduce the likelihood of low GPs` self-confidence in prescribing SGLT2ins was “familiarity with the side effects of these medications” (OR = 0.03), while factors that increased this likelihood were: “being familiar with GLP-1 RAs` side effects” (OR = 4.8), “an insufficient knowledge and experience of GPs in adjusting two target outcome measures to the same patient” (OR = 2.2), and “the GPs` assumption that the new guidelines` protocol which separates two target outcome measures is useful only in some cases but not in all” (OR = 5.4). Regarding GLP-1 RAs, only one factor – “familiarity of GPs with GLP-1 RAs side effects”, was shown to reduce the probability of GPs` low self-confidence in prescribing this group of medications (OR = 0.27). It is of the utmost importance to identify barriers the GPs face when prescribing these medications, as well as to suggest potential strategies to optimize their prescription.