Age-related Comorbidities Research Articles

A peptide-centric quantitative proteomics dataset for the phenotypic assessment of Alzheimer’s disease

Alzheimer’s disease (AD) is a looming public health disaster with limited interventions. Alzheimer’s is a complex disease that can present with or without causative mutations and can be accompanied by a range of age-related comorbidities. This diverse presentation makes it difficult to study molecular changes specific to AD. To better understand the molecular signatures of disease we constructed a unique human brain sample cohort inclusive of autosomal dominant AD dementia (ADD), sporadic ADD, and those without dementia but with high AD histopathologic burden, and cognitively normal individuals with no/minimal AD histopathologic burden. All samples are clinically well characterized, and brain tissue was preserved postmortem by rapid autopsy. Samples from four brain regions were processed and analyzed by data-independent acquisition LC-MS/MS. Here we present a high-quality quantitative dataset at the peptide and protein level for each brain region. Multiple internal and external control strategies were included in this experiment to ensure data quality. All data are deposited in the ProteomeXchange repositories and available from each step of our processing.

Osteoporosis remission via an anti-inflammaging effect by icariin activated autophagy

The pace of bone formation slows down with aging, which leads to the development of osteoporosis. In addition to senescent bone marrow mesenchymal stem cells (S-BMSCs), senescent macrophages (S-MΦs) present in the bone marrow produce numerous inflammatory cytokines that contribute to the inflammaged microenvironment and are involved in the development of osteoporosis. Although autophagy activation has shown a significant anti-aging effect, its influence on inflammaging and its role in osteoporosis treatment remain unclear. Traditional Chinese herbal medicine contains bioactive components that exhibit remarkable advantages in bone regeneration. We have demonstrated that icariin (ICA), a bioactive component of traditional Chinese herbal medicine, activates autophagy, exerts a significant anti-inflammaging effect on S-MΦs, and rejuvenates osteogenesis of S-BMSCs, thereby alleviating bone loss in osteoporotic mice. The transcriptomic analysis further reveals that the TNF-α signaling pathway, which is significantly associated with the level of autophagy, regulates this effect. Moreover, the expression of senescence-associated secretory phenotype (SASP) is significantly reduced after ICA treatment. In summary, our findings suggest that bioactive components/materials targeting autophagy can effectively modulate the inflammaging of S-MΦs, offering an innovative treatment strategy for osteoporosis remission and various age-related comorbidities.

High-dose-rate brachytherapy at 3 Gy per fraction for lip carcinoma: Treatment outcomes and toxicity at 5-years

PURPOSELow-dose-rate brachytherapy (LDR-BT) is a well-established treatment for lip cancer. High-dose-rate (HDR)-BT is a promising alternative to LDR-BT, but data are limited. In this context, we retrospectively evaluated treatment outcomes in a series of patients who underwent HDR-BT for lip carcinoma between 2003 and 2021. MATERIALS AND METHODSA total of 32 patients were included in this study, with a median age of 73.5 years (range, 61 – 88). The indications for HDR-BT were as follows: primary treatment (n = 17), adjuvant treatment (n = 3), and recurrent disease after surgery (n = 12). The prescribed dose was 18 fractions of 3 Gy administered twice daily. RESULTSAt a median followup of 45 months (range, 12 -232), the 5-year local recurrence-free interval was 96.9% (95% CI: 90.9–100%), the disease-free interval was 85% (95% CI: 70.9–99.1), and 5-year overall survival was 64.7% (95% CI: 44.7–84.8). Eleven patients died, all on age related comorbidities. Acute toxicity manifested as G1 dry desquamation in 6 patients (18.8%), G2 erythema in 10 patients (31.2%) and G3 confluent moist desquamation in 16 patients (50%). Late complications included G1 fibrosis (100% of cases). G1 and G2 depigmentation was observed in 8 (25%) and 6 (18%) patients, G1 telangiectasia occurred in 5 patients (16%). CONCLUSIONSThese data support the use of HDR-BT for lip cancer. The dose and fractionation schedule used in this study (18 fractions x 3 Gy twice daily) seems to be effective and safe.

Chronic brain damage in HIV-infected individuals under antiretroviral therapy is associated with viral reservoirs, sulfatide release, and compromised cell-to-cell communication.

HIV infection has become a chronic and manageable disease due to the effective use of antiretroviral therapies (ART); however, several chronic aging-related comorbidities, including cognitive impairment, remain a major public health issue. However, these mechanisms are unknown. Here, we identified that glial and myeloid viral reservoirs are associated with local myelin damage and the release of several myelin components, including the lipid sulfatide. Soluble sulfatide compromised gap junctional communication and calcium wave coordination, essential for proper cognition. We propose that soluble sulfatide could be a potential biomarker and contributor to white matter compromise observed in HIV-infected individuals even in the current ART era.

Critical Environmental Limits for Human Thermoregulation in the Context of a Changing Climate.

Human-caused climate change has increased the average temperature of the Earth by over 1°C since the 19th century with larger increases expected by 2100 due to continued human influence. This change in mean ambient temperature has had nonlinear effects, resulting in more high temperature extremes, i.e., heat waves, that have increased in frequency, duration, and magnitude. Additional occurrences of humid heatwaves have significantly affected human health due to the physiological strain associated with a relative inability for evaporative cooling. Inability to efficaciously cool the body, whether during passive heat exposure or physical activity, not only leads to elevated core temperatures but also places strain on the cardiovascular system, often exacerbating age-related co-morbidities. As part of the PSU HEAT (Pennsylvania State University - Human Environmental Age Thresholds) Project, a progressive environmental strain protocol has been developed to determine critical environmental limits - combinations of ambient temperature and humidity -- associated with uncompensable heat stress and intractable rises in core temperature (Tc). These human heat balance thresholds, well below those originally theorized by climatologists, have been surpassed in recent heatwaves and be exceeded on a more regular basis in the future, providing additional impetus to the urgency of adaptative measures and climate change mitigation.

The Natural Stilbenoid (-)-Hopeaphenol Inhibits HIV Transcription by Targeting Both PKC and NF-κB Signaling and Cyclin-Dependent Kinase 9.

Despite effective combination antiretroviral therapy (cART), people living with HIV (PLWH) continue to harbor replication-competent and transcriptionally active virus in infected cells, which in turn can lead to ongoing viral antigen production, chronic inflammation, and increased risk of age-related comorbidities. To identify new agents that may inhibit postintegration HIV beyond cART, we screened a library of 512 pure compounds derived from natural products and identified (-)-hopeaphenol as an inhibitor of HIV postintegration transcription at low to submicromolar concentrations without cytotoxicity. Using a combination of global RNA sequencing, plasmid-based reporter assays, and enzyme activity studies, we document that hopeaphenol inhibits protein kinase C (PKC)- and downstream NF-κB-dependent HIV transcription as well as a subset of PKC-dependent T-cell activation markers, including interleukin-2 (IL-2) cytokine and CD25 and HLA-DRB1 RNA production. In contrast, it does not substantially inhibit the early PKC-mediated T-cell activation marker CD69 production of IL-6 or NF-κB signaling induced by tumor necrosis factor alpha (TNF-α). We further show that hopeaphenol can inhibit cyclin-dependent kinase 9 (CDK9) enzymatic activity required for HIV transcription. Finally, it inhibits HIV replication in peripheral blood mononuclear cells (PBMCs) infected in vitro and dampens viral reactivation in CD4+ cells from PLWH. Our study identifies hopeaphenol as a novel inhibitor that targets a subset of PKC-mediated T-cell activation pathways in addition to CDK9 to block HIV expression. Hopeaphenol-based therapies could complement current antiretroviral therapy otherwise not targeting cell-associated HIV RNA and residual antigen production in PLWH.

Antimicrobial Nano-Zinc Oxide Biocomposites for Wound Healing Applications: A Review

Chronic wounds are a major concern for global health, affecting millions of individuals worldwide. As their occurrence is correlated with age and age-related comorbidities, their incidence in the population is set to increase in the forthcoming years. This burden is further worsened by the rise of antimicrobial resistance (AMR), which causes wound infections that are increasingly hard to treat with current antibiotics. Antimicrobial bionanocomposites are an emerging class of materials that combine the biocompatibility and tissue-mimicking properties of biomacromolecules with the antimicrobial activity of metal or metal oxide nanoparticles. Among these nanostructured agents, zinc oxide (ZnO) is one of the most promising for its microbicidal effects and its anti-inflammatory properties, and as a source of essential zinc ions. This review analyses the most recent developments in the field of nano-ZnO-bionanocomposite (nZnO-BNC) materials-mainly in the form of films, but also hydrogel or electrospun bandages-from the different preparation techniques to their properties and antibacterial and wound-healing performances. The effect of nanostructured ZnO on the mechanical, water and gas barrier, swelling, optical, thermal, water affinity, and drug-release properties are examined and linked to the preparation methods. Antimicrobial assays over a wide range of bacterial strains are extensively surveyed, and wound-healing studies are finally considered to provide a comprehensive assessment framework. While early results are promising, a systematic and standardised testing procedure for the comparison of antibacterial properties is still lacking, partly because of a not-yet fully understood antimicrobial mechanism. This work, therefore, allowed, on one hand, the determination of the best strategies for the design, engineering, and application of n-ZnO-BNC, and, on the other hand, the identification of the current challenges and opportunities for future research.

Among Gerontogens, Heavy Metals Are a Class of Their Own: A Review of the Evidence for Cellular Senescence.

Advancements in modern medicine have improved the quality of life across the globe and increased the average lifespan of our population by multiple decades. Current estimates predict by 2030, 12% of the global population will reach a geriatric age and live another 3-4 decades. This swelling geriatric population will place critical stress on healthcare infrastructures due to accompanying increases in age-related diseases and comorbidities. While much research focused on long-lived individuals seeks to answer questions regarding how to age healthier, there is a deficit in research investigating what aspects of our lives accelerate or exacerbate aging. In particular, heavy metals are recognized as a significant threat to human health with links to a plethora of age-related diseases, and have widespread human exposures from occupational, medical, or environmental settings. We believe heavy metals ought to be classified as a class of gerontogens (i.e., chemicals that accelerate biological aging in cells and tissues). Gerontogens may be best studied through their effects on the "Hallmarks of Aging", nine physiological hallmarks demonstrated to occur in aged cells, tissues, and bodies. Evidence suggests that cellular senescence-a permanent growth arrest in cells-is one of the most pertinent hallmarks of aging and is a useful indicator of aging in tissues. Here, we discuss the roles of heavy metals in brain aging. We briefly discuss brain aging in general, then expand upon observations for heavy metals contributing to age-related neurodegenerative disorders. We particularly emphasize the roles and observations of cellular senescence in neurodegenerative diseases. Finally, we discuss the observations for heavy metals inducing cellular senescence. The glaring lack of knowledge about gerontogens and gerontogenic mechanisms necessitates greater research in the field, especially in the context of the global aging crisis.

Association of COVID-19 with Comorbidities: An Update.

Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which was identified in Wuhan, China in December 2019 and jeopardized human lives. It spreads at an unprecedented rate worldwide, with serious and still-unfolding health conditions and economic ramifications. Based on the clinical investigations, the severity of COVID-19 appears to be highly variable, ranging from mild to severe infections including the death of an infected individual. To add to this, patients with comorbid conditions such as age or concomitant illnesses are significant predictors of the disease's severity and progression. SARS-CoV-2 enters inside the host cells through ACE2 (angiotensin converting enzyme2) receptor expression; therefore, comorbidities associated with higher ACE2 expression may enhance the virus entry and the severity of COVID-19 infection. It has already been recognized that age-related comorbidities such as Parkinson's disease, cancer, diabetes, and cardiovascular diseases may lead to life-threatening illnesses in COVID-19-infected patients. COVID-19 infection results in the excessive release of cytokines, called "cytokine storm", which causes the worsening of comorbid disease conditions. Different mechanisms of COVID-19 infections leading to intensive care unit (ICU) admissions or deaths have been hypothesized. This review provides insights into the relationship between various comorbidities and COVID-19 infection. We further discuss the potential pathophysiological correlation between COVID-19 disease and comorbidities with the medical interventions for comorbid patients. Toward the end, different therapeutic options have been discussed for COVID-19-infected comorbid patients.

Efficacy and Safety of Dupilumab Maintained in Adults ≥ 60 Years of Age with Moderate-to-Severe Atopic Dermatitis: Analysis of Pooled Data from Four Randomized Clinical Trials.

Adults aged ≥ 60 years are often underrepresented in atopic dermatitis (AD) clinical trials; age-related comorbidities may impact treatment efficacy and safety. The aim was to report dupilumab efficacy and safety in patients aged ≥ 60 years with moderate-to-severe AD. Data were pooled from four randomized, placebo-controlled dupilumab trials of patients with moderate-to-severe AD (LIBERTY AD SOLO 1 and 2, LIBERTY AD CAFÉ, and LIBERTY AD CHRONOS) and stratified by age (<60 [N = 2261] and ≥ 60 [N = 183] years). Patients received dupilumab 300 mg every week (qw) or every 2 weeks (q2w), or placebo with/without topical corticosteroids. Post hoc efficacy at week 16 was examined using broad categorical and continuous assessments of skin lesions, symptoms, biomarkers, and quality of life. Safety was also assessed. In the ≥ 60-year-old group at week 16, a greater proportion of dupilumab-treated patients achieved an Investigator's Global Assessment score of 0/1 (q2w: 44.4%; qw: 39.7%) and 75% improvement in Eczema Area and Severity Index (63.0%; 61.6%) versus placebo (7.1% and 14.3%, respectively; P < 0.0001). Type 2 inflammation biomarkers (immunoglobulin E and thymus and activation-regulated chemokine) were also significantly reduced in dupilumab- versus placebo-treated patients (P < 0.01). Results were similar in the < 60-year-old group. The exposure-adjusted incidences of adverse events in dupilumab-treated patients were generally similar to those receiving placebo, with numerically fewer treatment-emergent adverse events in the dupilumab-treated ≥ 60-year-old group versus placebo. There were fewer patients in the ≥ 60-year-old group; post hoc analyses. Dupilumab improved AD signs and symptoms in patients aged ≥ 60 years; results were comparable to those in patients aged <60 years. Safety was consistent with the known dupilumab safety profile. ClinicalTrials.gov: NCT02277743, NCT02277769, NCT02755649, NCT02260986. Does dupilumab benefit adults aged 60 years and older with moderate-to-severe atopic dermatitis?(MP4 20,787 KB).

Fear of COVID-19 is associated with trust, subjective numeracy, and differentially with loneliness in older versus younger adults.

The emotional impacts of the COVID-19 pandemic and resulting public health emergency are only beginning to be understood. We assessed the contributions of emotional and cognitive factors and age-related comorbidities to greater COVID-19 fear in a community dwelling sample of 142 younger (Mage = 19.63, SDage = 2.59) and 157 older (Mage = 72.01, SDage = 7.06) adults, between July 2020 and July 2021. We hypothesized that individuals with increased loneliness, depression, and/or decreased subjective numeracy (SN) and interpersonal trust would experience more COVID-19 fear. We also predicted that females and older adults would experience more COVID-19 fear given that age-related comorbidities are associated with increased illness severity. Results showed that the extent of loneliness in older adults was more strongly related to fear of COVID-19 than it was in younger adults (β = 0.197, p = 0.016), and poorer SN was associated with increased COVID-19 fear in both age groups (β = -0.138, p = 0.016). Further, higher interpersonal mistrust was associated with increased COVID-19 fear (β = 0.136, p = 0.039), as was identifying as female (β = 0.137, p = 0.013). Given that self-described poor numeracy was a marker for greater COVID-19 fear, investigators and policy makers might consider mitigation opportunities addressing data literacy requirements imposed by the media. Further, outreach to mitigate loneliness, particularly of the elderly, might effectively lessen the negative psychological impact of this ongoing public health crisis.

Serum testosterone and sex hormone-binding globulin are inversely associated with leucocyte telomere length in men: a cross-sectional analysis of the UK Biobank study.

Older men on an average have lower testosterone concentrations, compared with younger men, and more age-related comorbidities. Whether lower testosterone concentrations contribute to biological ageing remains unclear. Shorter telomeres are a marker for biological age. We tested the hypothesis that testosterone concentrations are associated with leucocyte telomere length (LTL), in middle- to older-aged men. Cross-sectional analysis of the UK Biobank study, involving community-dwelling men aged 40-69 years. Serum testosterone and sex hormone-binding globulin (SHBG) were assayed. Free testosterone was calculated (cFT). Leucocyte telomere length was measured using polymerase chain reaction. Multivariable models were used to assess associations of hormones with standardised LTL. In 167 706 men, median age 58 years, adjusting for sociodemographic, lifestyle, and medical factors, total testosterone was inversely associated with standardised LTL, which was 0.09 longer (95% confidence interval [CI], 0.08-0.10, P < .001) in men with total testosterone at median of lowest quintile [Q1] vs highest [Q5]. This relationship was attenuated after additional adjustment for SHBG (0.03 longer, CI = 0.02-0.05, P = .003). The association between cFT and LTL was similar in direction but lower in magnitude. In multivariable analysis, SHBG was inversely associated with standardised LTL, which was 0.12 longer (CI = 0.10-0.13, P < .001) for SHBG at median Q1 vs Q5. Results were similar with testosterone included in the model (0.10 longer, CI = 0.08-0.12, P < .001). Total testosterone and SHBG were independently and inversely associated with LTL. Men with higher testosterone or SHBG had shorter telomeres, arguing against a role for testosterone to slow biological ageing in men.

Stem Cell Treatments in Preclinical Relevant Stroke Models.

Since stroke has limited treatment options, an active search for new therapeutic approaches is required. Initial excitement of using cell-based therapies to stimulate recovery processes in the ischemic brain turned into a more measured perspective, acknowledging obstacles related to the unfavorable environments associated in part with aging. Given the predominance of stroke in older populations, evaluating the effectiveness of cell therapies in aged brain environments is essential and clinically relevant. Despite a common perception of the aged brain being resistant to regeneration, recent research with neural precursor cells and bone marrow-derived mesenchymal stem cells indicates that cell-based therapy can promote plasticity and remodeling in the aged rat brain. However, significant differences in the aged brain compared to the young brain, such as expedited progression of ischemic injury to brain infarction, decreased rate of endogenous neurogenesis, and delayed onset of neurological recovery, must be noted. The effectiveness of cell-based therapies may further be connected to age-related comorbidities such as diabetes or hyperlipidemia, potentially leading to maladaptive or impaired brain remodeling. These age-related factors need careful consideration in the clinical application of restorative therapies for stroke.

How we manage cardiovascular disease in patients with hemophilia.

With the striking advances in hemophilia care that have materialized particularly in the last two decades, an increasing number of persons with hemophilia (PWH) have achieved a quality of life and life expectancy very close to that of unaffected individuals. With aging, a growing number of PWH develop age-related co-morbidities, including cancer and cardiovascular disease. The latter (particularly coronary artery disease and atrial fibrillation) represent a new challenge for the hemophilia treatment centers because their management implies a delicate balance between the thrombotic risk and bleeding tendency, that is further enhanced by the concomitant use of antithrombotic agents. Because evidence from clinical trials is lacking, the management of PWH with cardiovascular diseases is mostly based on expert opinions, personal experiences, and the adaptation of the evidence stemming from studies on people without hemophilia. In this article, we focus on how to manage coronary artery disease and atrial fibrillation in patients with hemophilia.

High patient satisfaction and increased physical activity following a remote multidisciplinary team multiple myeloma clinic

PurposePatients with multiple myeloma suffer from disease-related complications such as bone destruction, toxicities from repeated therapies and age-related co-morbidities. With improved treatment options, patients are living longer and have specific survivorship needs such as low exercise levels that need to be addressed. In this study, we designed, implemented and evaluated a multidisciplinary team (MDT) myeloma clinic that provided participants with tailored exercise and lifestyle advice.MethodsThe Promoting Individualised Self-Management and Survivorship (PrISMS) clinic was set up in two UK myeloma centres. This remote MDT clinic comprised of a doctor, a nurse specialist and a physiotherapist. Patients were required to complete blood tests and a questionnaire about their symptoms and concerns before each consultation. Patient-reported outcome measures were captured using validated questionnaires. Patient feedback was collected using a specially designed survey and structured telephone interviews.ResultsSixty-one patients were enrolled in the pilot clinic with 210 consultations held during the study period. Nine patients had disease progression and were referred safely back to face-to-face clinics. There was a significant improvement in patients’ exercise score (p = 0.02) after PrISMS clinic. Patient satisfaction was high, with 83% feeling more confident in self-managing myeloma after PrISMS clinic.ConclusionPrISMS clinic is safe and feasible, with high patient compliant and acceptability. It empowers patients to self-manage their condition and encourages physical activity, which is associated with improved quality of life and fatigue level. Future randomised controlled trials will help to confirm its benefits on patient clinical outcomes and cost-effectiveness.

Abstract B012: Advanced epigenetic aging in non-AIDS-defining cancer patients living with HIV

Abstract Background. With widespread use of antiretroviral therapy, people with HIV (PWH) are living longer and are now at risk for age-related co-morbidities, including non-AIDS defining cancers (NADCs). Given this epidemiological trend, it is important to understand how prolonged HIV infection may relate to molecular features of aging that can impact cancer risk or outcomes. Methyl groups naturally accumulate on human DNA over time, and methylation patterns can be translated into metrics of accelerated aging. We compared epigenetic measures of aging between PWH receiving treatment for an NADC and matched HIV-uninfected NADC patients at Moffitt Cancer Center in Tampa, Florida. Methods. We identified PWH diagnosed with a non-AIDS defining solid tumor from 2004 to 2021 were identified. To be included, patients needed to have an archived specimen amenable for DNA extraction (whole blood, buffy coat, or PBMC) collected within 1 year of cancer diagnosis. HIV-uninfected matches were identified in a similar manner and matched by tumor site, reported age (+/- 5 years), tumor sequence (primary vs. non-primary), and treatment status. Extracted DNA was assayed using the Illumina MethylationEPIC BeadChip, which incorporates data from 850,000 CpG sites across the genome. Data were translated into a biological age using the epiTOC2 clock, which estimates the number of total number of stem cell divisions, and GrimAge, associated with mortality. Methylation data were also deconvoluted to determine immune cell composition (CD4+ T-cells, CD8+ T-cells, B-cells, neutrophils, natural killer cells, monocytes, basophils, eosinophils). Epigenetic age and immune cell proportions were compared across HIV status using Wilcoxan rank sum testing. Age acceleration was calculated as the difference (residuals from a linear model) in the observed age for PWH and a NADC diagnosis, compared to the predicted age based on HIV-uninfected NADC patients, using both unadjusted and immune-cell adjusted linear models. Results. DNA methylation was assessed in 65 NADC PWH and HIV and 64 HIV-uninfected NADC patients. Epigenetic age assessed using the epiTOC2 and GrimAge clocks was significantly elevated in PWH (p&amp;lt;0.001 and p=0.02, respectively). When methylation data was used to de-convolute immune cell composition, the proportion of CD4+ T-cells and neutrophils was significantly (P&amp;lt;0.05) lower in PWH, while the proportions of memory B-cells and CD8+ T-cells were higher. Epigenetic age was accelerated in PWH compared to HIV-uninfected patients using both epiTOC2 and GrimAge clocks, with the difference in the GrimAge clock remaining significant after adjustment for immune cell composition (P-value&amp;lt;0.01). Conclusions. The results of this study demonstrated age acceleration in PWH with a NADC diagnosis compared to their HIV-uninfected counterparts. As cancer is now the leading cause of non-AIDS death in PWH, research into the prognostic implications of these differences is warranted. Citation Format: Anna E. Coghill, Brittney Dickey, Ryan Putney, Anders Berglund. Advanced epigenetic aging in non-AIDS-defining cancer patients living with HIV [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr B012.

The Growing Epidemic of Opioid Use Disorder in the Elderly and Its Treatment: A Review of the Literature.

Objective: US demographic trends show an increasing proportion of adults aged > 65 years old, approximately 1 million of whom are living with an opioid use disorder (OUD). OUD may be particularly problematic in this age group due to age-related pain syndromes and comorbidities that increase the risk of side effects, overdose, and death. The objective of this review was to assess the safety and efficacy of medications for OUD (MOUD) in the elderly.Data Sources: A systematic search of the literature in PubMed, CINAHL, MEDLINE, Embase, and Cochrane Library databases was conducted from January 1992 through October 2021. The following terms were used: elderly, older adults, opioid use disorder, opioid dependence, buprenorphine, methadone, and medication-assisted treatment.Study Selection: The search yielded 633 results. After following PRISMA guidelines and careful manual exclusion, 13 studies were selected for the review. No studies examining use of buprenorphine were identified for MOUD.Results: The application of methadone for MOUD in the elderly shows that use is limited by preexisting conditions such as cardiac conduction abnormalities, which are more prevalent in the elderly than in the general population. Buprenorphine and naltrexone have been documented to have fewer interactions and potentially lethal adverse effects compared to methadone.Conclusion: Future studies should focus on the application of buprenorphine or naltrexone for MOUD in the elderly.

Nature can still be the strongest help against aging and neurodegeneration: the sirtuins way.

Nature can still be the strongest help against aging and neurodegeneration: the sirtuins way.

Bioactive compounds in the nutrition of peri- and postmenopausal women within the concept of 4P-medicine

An updated consensus statement from the European Menopause and Andropause Society noted that a woman's quality of life may decline during peri- and post-menopause as a result of various menopausal symptoms and age-related comorbidities. The purpose of the work was to assess the possibility of using bioactive compounds in periand postmenopausal women to prevent the development of menopausal complications and chronic diseases associated with aging. Material and methods. Literature search was carried out using PubMed, Google Scholar, ResearchGate, RSCI databases mainly over the past 10 years, with the exception of works of fundamental importance, according to the keywords "perimenopause", "postmenopause", "Affron® saffron extract", "special extract ERr 731". Results. The use of diet, dietary supplements including those containing extracts of saffron (Affron®) and Siberian rhubarb (ERr 731) and their biologically active substances, has a versatile effect on the correction of menopausal disorders due to the impact on various pathogenetic pathways of their development and can be used in women in this period as a phytonutrient support. Conclusion. The combined use of saffron and Siberian rhubarb extracts is promising from the point of view of correcting the female state during peri- and postmenopause, taking into account the pathogenetic moments of the development of menopausal complications and chronic diseases associated with aging.

Approach to acute psychosis in older adults.

Approach to acute psychosis in older adults.