Development Of Age-related Diseases Research Articles

Exploring the expression profiles of serum inflammatory proteins and potential anti-aging targets in Chinese long-living people.

Chronic inflammation (inflammaging) is one of the important reasons for the development of age-related diseases and aging. Carrying out aging research and mining inflammatory markers can develop anti-aging intervention targets, thus promoting healthy aging. By comparing the levels of inflammatory proteome in the serum of Chinese long-living people over 90 years and elderly aged 60~79 which was detected by Olink platform, this study found that some pro-inflammatory or pro-aging proteins increased significantly in the long-living people, such as CXCL9, accompanied by a significant increase in the levels of several anti-inflammatory or anti-aging proteins, including FGF19 and FGF23, which confirmed that compared with elderly people, pro-inflammatory and anti-inflammatory (pro-aging and anti-aging) tend to be balanced in long-living people, thus reducing the risk of age-related diseases and prolonging the life span of the elderly. These differently expressed proteins could serve as therapeutic targets and monitoring indicators for anti-aging. At the same time, a few inflammatory protein markers, especially CXCL9 and OPG, could distinguish long-living and elderly correctly which could be used to predict lifespan combined with other anti-aging markers.

Black Chokeberry (Aronia melanocarpa) Juice Supplementation Improves Oxidative Stress and Aging Markers in Testis of Aged Rats.

Spermatogenesis is a process that continues until the end of an individual's life, although with reduced activity with advancing age. Inflammation, oxidation, and apoptosis are events considered as predictors of pathogenesis and the development of age-related diseases observed in aged testes. The use of natural compounds with antioxidant and anti-inflammatory properties has a beneficial effect on the inflammatory and oxidative status of the aged testis. The aim of this study was to determine the effect of supplementation with antioxidant-rich black chokeberry (Aronia melanocarpa) juice on several markers of oxidative stress and aging in rat testis. In total, 24 male Wistar rats were divided into three experimental groups: young controls aged 2 months, old controls aged 27 months, and 27-month-old rats supplemented with black chokeberry juice at a dose of 10 mL/kg for 3 months. A. melanocarpa juice supplementation led to reduced oxidative stress, manifested by increased immunoexpression of nNOS, eNOS, and MAS1 in the seminiferous tubules and in the Leydig cells. The morphometrically determined tubule structure data showed no significant differences between the three groups. However, the intensity of the immunoreaction for TRK-C and NT3 in Leydig cells was demonstrably higher in the supplemented old animals compared with the old controls. There was a significantly higher number of blood vessels around the seminiferous tubules in the supplemented animals compared to the old controls. These data indicate that supplementation with A. melanocarpa juice slows down aging processes in the testis and preserves the functional activity of Leydig cells.

DRUGS WITH SENOLYTIC ACTIVITY: PROSPECTS AND POSSIBLE LIMITATIONS

The search and testing of drugs with senolytic activity is one of the new directions in gerontology. The number of “senescent” cells that increases with age contributes to the development of age-related diseases and chronic non-infectious inflammation. Removing “senescent” cells or suppressing their influence on surrounding tissues seems a logical step to improve the quality of life and, possibly, prolong lifespan. However, drugs that have senolytic and senomorphic activity in model systems cause the development of a number of side effects in clinical trials. In this review, we consider the main advances in the field of senotherapy, the prospects for the use of senotherapy drugs, and the limitations that researchers and clinicians may encounter.

Long Non-coding RNA ANRIL and Its Role in the Development of Age-Related Diseases.

ANRIL is known as a lncRNA that has many linear and circular isoforms and its polymorphisms are observed to be associated with the pathogenesis of many diseases including age-related diseases. Age-related diseases including atherosclerosis, ischemic heart disease, and Alzheimer's and Parkinson's disease are the most common cause of mortality in both developed and undeveloped countries and that is why a better understanding of their pathogenesis and underlying mechanisms is necessary for controlling their healthcare burden.In this review, we aim to gather the data of researches which have investigated the role of ANRIL in aging and its related diseases. The conclusions of this paper might give a new insight for decreasing the mortality rate of these diseases.

A double inducible cell ablation system for eliminating senescent astrocytes via apoptosis.

Cell senescence stands as a principal risk factor for various neurodegenerative diseases, with astrocytic senescence emerging as a potentially pivotal player in the pathogenesis of aging and neurodegenerative disorders. Clearing senescent astrocytes holds promise as a potential therapeutic approach for senescence-related diseases. In this study, we designed and constructed two plasmids aimed at inducing apoptosis in senescent astrocytes. This was achieved through the ligation of FKBP (FK506-binding protein) and FRB (FKBP and FKBP rapamycin binding domain) and the formation of caspase8 dimers, thereby achieving the purpose of eliminating senescent astrocytes. The developed vector system demonstrates a specifically capability to induce apoptosis in aging astrocytes, offering a targeted approach to eliminate these cells. The utilization of the double -inducible suicide gene system provides a versatile tool forstimulating cell apoptosis and inhibiting cellular senescence. This system proves valuable in exploring the intrinsic roles and molecular mechanisms of senescent cells in the occurrence and development of aging-related diseases. Ultimately, it offers a potential avenue for developing an efficient treatment system for such conditions.

Association of immune inflammatory biomarkers with pathological complete response and clinical prognosis in young breast cancer patients undergoing neoadjuvant chemotherapy.

The persistence of inflammatory stimulus has a tight relationship with the development of age-related diseases, ultimately resulting in a gradual escalation in the prevalence of tumors, but this phenomenon is rare in young cancer patients. Breast cancer arising in young women is characterized by larger tumor diameters and more aggressive subtypes, so neoadjuvant chemotherapy (NACT) can be especially appropriate for this population. Immune inflammatory biomarkers have been reportedly linked to the prognosis of some malignant tumor types, with varying results. In this study, we investigated the possible predictive value of blood-based markers in young breast cancer patients undergoing NACT, in addition to the association between the clinicopathological features and prognosis. From December 2011 to October 2018, a total of 215 young breast cancer patients referred to Harbin Medical University Cancer Hospital received NACT and surgery were registered in this retrospective study. The pretreatment complete blood counts were used to calculate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV). NLR, PLR, MLR, and PIV optimal cut-off values were 1.55, 130.66, 0.24, and 243.19, as determined by receiver operating characteristic analysis. Multivariate analysis revealed that PIV, HR status, HER-2 status, and Ki-67 index were all independent predictive factors for pathological complete response. Subgroup analysis revealed that young breast cancer patients in the population characterized by low PIV and HR negative group were more likely to get pCR (P=0.001). The five-year overall survival (OS) rate was 87.9%, and Cox regression models identified PIV as independently related to OS. In the present study, the pretreatment PIV was found to be a useful prognostic indicator for pCR and long-term survival in young breast cancer patients undergoing NACT. High immune and inflammation levels, MLR and PIV were connected to poor clinical prognosis in young breast cancer patients. PIV is a promising biomarker to guide strategic decisions in treating young breast cancer.

Proanthocyanidins supplemented diet alter anti-aging-markers and improved lifespan in Drosophila melanogaster model

BackgroundIt is unequivocally believed that phenolics and flavonoids from fruits and vegetables hold robust prevention potentials against age-related disease development through their abundant hydroxyl groups. This study explored the potential neuromuscular enhancement and anti-aging effects of dietary supplemented proanthocyanidins-rich fraction from Tamarindus indica on Drosophila melanogaster model. One- to three-day-old male and female D. melanogaster were fed with a proanthocyanidins-rich fraction-supplemented diet for 7 days at two different concentrations. Following the effective dose determination, longevity assay (rate of survival), behavioral assay (negative geotaxis and eclosion), and biochemical assays (aging and antioxidant enzymes activities) were conducted to assess the fraction’s longevity, antioxidant, and anti-aging effects on D. melanogaster model.ResultThe results showed a significant (p < 0.05) improvement in the rate of emergence and lifespan of the flies fed with proanthocyanidins-rich fraction-supplemented diet at both concentrations (1.5 mg/g and 2.5 mg/g) compared to the normal control. A significant decrease in acetylcholinesterase (AChE) activity and the level of caspase-3 and caspase-9 were observed in the D. melanogaster flies fed with the fraction-containing diet when compared with the normal control. The supplemented diet also significantly increases the activity of catalase, superoxide dismutase (SOD), and glutathione-s-transferase (GST) in a concentration-dependent manner but not nicotinamide quinone oxidoreductase one (NQO1) in D. melanogaster upon comparison with the normal control.ConclusionThe observable changes in the experiment were attributed to the T. indica-derived proanthocyanidins, flavonoids with robust biological activities. The flavonoid-rich fraction proved its potential by enhancing the antioxidant system in D. melanogaster via the increase in the activities of some of the phase II antioxidant enzymes. The present study provides more insights into the wider perspectives of societies on the use of plant-derived natural compounds as the potential approach toward prevention against aging and age-related morbidities which enhance wellness and the quality of life in humans and animals.

The Potential of Using Cochayuyo (Durvillaea incurvata) Extract Obtained by Ultrasound-Assisted Extraction to Fight against Aging-Related Diseases.

The world's population is in a demographical transition, with an increase in the number of older adults and prevalence of diseases related to aging. This study evaluated in vitro the potential of using Durvillaea incurvata extract (extracted using ultrasound-assisted extraction) to inhibit key enzymes associated with the development of age-related diseases. Our results show that an extract extracted via ultrasound-assisted extracted, as well as an extract conventional extracted from Durvillaea incurvata, presented antidiabetes potential by exhibiting inhibitory activity against α-glucosidase (91.8 ± 1.0% and 93.8 ± 0.3%, respectively, at 500 µg/mL) and α-amylase (42.2 ± 1.4% and 61.9 ± 0.9%, respectively, at 1500 µg/mL) enzymes related to starch digestion and postprandial glycemic response. Also, the extracts showed inhibitory activity against the enzymes acetylcholinesterase (51.5% and 50.8%, respectively, at 500 µg/mL) and butyrylcholinesterase (32.8% and 34.4%, respectively, at 0.5 mg/mL), the biomarkers associated with Alzheimer's disease, and angiotensin-converting enzyme (98.7 ± 7.4% and 93.0 ± 3.4%, respectively, at 2.0 mg/mL), which is key in the regulation of vascular tone and blood pressure and helps to prevent the development of hypertension. In conclusion, the extract of Durvillaea incurvata obtained from ultrasound-assisted extraction has the potential to prevent the development of age-related pathologies such as diabetes, Alzheimer's disease, and hypertension.

DEVELOPING A PROTOCOL TO ASSESS EXPOSURE TO ENVIRONMENTAL POLLUTANTS AMONG OLDER ADULT WOMEN IN SOUTHEAST MICHIGAN

Abstract Environmental pollutants, including PFAS, phthalates, and parabens, contribute to the development of age-related diseases like cancer, cardiometabolic disease, and neurodegenerative diseases. Unfortunately, these chemicals are common in everyday exposures, including drinking water, personal care products (PCPs), non-stick cookware, and food packaging. Exposures to these pollutants may be high in communities that have encountered structural disadvantages; neighborhood disinvestment and decaying infrastructure can make exposures to these pollutants more likely, thus increasing the burden of age-related disease in these communities. Interventions that reduce exposures to these chemicals may prevent or delay the onset of age-related disease, especially in groups experiencing poorer health outcomes because of structural racism and discrimination. To explore the feasibility of a behavior change intervention for older adults that reduces exposure to harmful chemicals in PCPs, a protocol was developed to: 1) Assess attitudes, knowledge, and behaviors related to environmental pollutants via questionnaire; 2) Characterize individual-level ‘exposomes’, the unique mixture of chemicals a person encounters in their everyday lives, by wearing a silicone wristband; 3) Measure environmental exposures in serum. Data collection will begin in September 2023 among older adult women who have participated in the Study of Women’s Health Across the Nation (SWAN) at the Michigan site. Older adults have accrued environmental exposures across their lifetimes, likely in a way that reflects patterns of structural disadvantage. While structural solutions are necessary to address issues of health equity, behavior change efforts can work in tandem to reduce harmful environmental exposures to improve the health of older adults.

On the wake of metformin: Do anti-diabetic SGLT2 inhibitors exert anti-aging effects?

Here we propose that SGLT2 inhibitors (SGLT2i), a class of drugs primarily used to treat type 2 diabetes, could also be repositioned as anti-aging senomorphic drugs (agents that prevent the extrinsic harmful effects of senescent cells). As observed for metformin, another anti-diabetic drug with established anti-aging potential, increasing evidence suggests that SGLT2i can modulate some relevant pathways associated with the aging process, such as free radical production, cellular energy regulation through AMP-activated protein kinase (AMPK), autophagy, and the activation of nuclear factor (NF)-kB/inflammasome. Some interesting pro-healthy effects were also observed on human microbiota. All these mechanisms converge on fueling a systemic proinflammatory condition called inflammaging, now recognized as the main risk factor for accelerated aging and increased risk of age-related disease development and progression. Inflammaging can be worsened by cellular senescence and immunosenescence, which contributes to the increased burden of senescent cells during aging, perpetuating the proinflammatory condition. Interestingly, increasing evidence suggested the direct effects of SGLT-2i against senescent cells, chronic activation of immune cells, and metabolic alterations induced by overnutrition (meta-inflammation). In this framework, we analyzed and discussed the multifaceted impact of SGLT2i, compared with metformin effects, as a potential anti-aging drug beyond diabetes management. Despite promising results in experimental studies, rigorous investigations with well-designed cellular and clinical investigations will need to validate SGLT2 inhibitors' anti-aging effects.

Klotho: a potential therapeutic target in aging and neurodegeneration beyond chronic kidney disease-a comprehensive review from the ERA CKD-MBD working group.

Klotho, a multifunctional protein, acts as a co-receptor in fibroblast growth factor 23 and exerts its impact through various molecular pathways, including Wnt, hypoxia-inducible factor and insulin-like growth factor 1 pathways. The physiological significance of Klotho is the regulation of vitamin D and phosphate metabolism as well as serving as a vital component in aging and neurodegeneration. The role of Klotho in aging and neurodegeneration in particular has gained considerable attention. In this narrative review we highlight several key insights into the molecular basis and physiological function of Klotho and synthesize current research on the role of Klotho in neurodegeneration and aging. Klotho deficiency was associated with cognitive impairment, reduced growth, diminished longevity and the development of age-related diseases in vivo. Serum Klotho levels showed a decline in individuals with advanced age and those affected by chronic kidney disease, establishing its potential diagnostic significance. Additionally, multiple medications have been demonstrated to influence Klotho levels. Therefore, this comprehensive review suggests that Klotho could open the door to novel interventions aimed at addressing the challenges of aging and neurodegenerative disorders.

SAT046 Canagliflozin Leads To Less Weight Gain, Confers Changes In The Gut Microbiota And Extends Life Span In Male C57BL6 Mice

Abstract Disclosure: E.E. Habeos: None. F. Filippopoulou: None. M. Kanakis: None. G.I. Habeos: None. N. Belmokhtar: None. P. Stathopoulou: None. G. Tsiamis: None. S. Taraviras: None. G. Lagoumintzis: None. D.V. Chartoumpekis: None. Introduction: SGLT2 inhibitors (SGLT2i) are widely prescribed drugs for the treatment of diabetes. Their beneficial health effects appear to be pleiotropic and are not limited to the amelioration of glycemic profile. The SGLT2i-induced glycosuria is suggested to provoke a metabolic shift that mimics the fasting response. Since calorie restriction has been shown to enhance longevity in mice, we hypothesized that treating mice with SGLT2i would also increase their life span. Methods: To this end, 4-months old male C57BL6 mice were fed with a standard chow diet (Control, n=83) or a diet supplemented with 200 mg/kg canagliflozin (Cana, n=92) and were observed up to the natural end of their life. Results: The canagliflozin-treated mice gained less weight over time. For instance, at the age of 10 months, the body weight of control mice was higher (means ± SEM: 33.1 ± 0.26 g) than the body weight of their canagliflozin-treated counterparts (means ± SEM: 31.4± 0.21 g; p&amp;lt;0.01). The development and severity of age-related cataracts were also examined at the age of 14 months, but no statistically significant difference was found in the severity score between the 2 groups. The survival curves of the control and the Cana mice diverged significantly, with the median survival of the control being 107.5 weeks versus 112.5 weeks of the Cana group (p=0.011). As the gut microbiome is known to change with age and be associated with the development of age-related diseases, feces were collected from 17-month-old mice (n=10 per group) and analysis of fecal bacterial 16S rRNA sequences was performed. Differences in beta diversity (diversity of bacterial species across samples) and relative abundance of bacterial species were noted between the Control and the Cana groups. Conclusions-Discussion: Our study highlights the effect of SGLT2i on longevity in a widely used mouse model (C57BL6). The underlying mechanisms leading to the enhancement of longevity are not clear yet. Some microbiota changes associated with the SGLT2i treatment, as described in other mouse models with enhanced longevity, warrant further investigation and analysis. It would be useful to extend these studies employing various SGLT2i with different potencies and selectivity against SGLT so as to determine if the observed effect on longevity is independent of the type of the drug. Presentation: Saturday, June 17, 2023

Adipose tissue as a therapeutic target for vascular damage in Alzheimer's disease.

Adipose tissue has recently been recognized as an important endocrine organ that plays a crucial role in energy metabolism and in the immune response in many metabolic tissues. With this regard, emerging evidence indicates that an important crosstalk exists between the adipose tissue and the brain. However, the contribution of adipose tissue to the development of age-related diseases, including Alzheimer's disease, remains poorly defined. New studies suggest that the adipose tissue modulates brain function through a range of endogenous biologically active factors known as adipokines, which can cross the blood-brain barrier to reach the target areas in the brain or to regulate the function of the blood-brain barrier. In this review, we discuss the effects of several adipokines on the physiology of the blood-brain barrier, their contribution to the development of Alzheimer's disease and their therapeutic potential. LINKED ARTICLES: This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc.

Effects of Vitamin E on the Gut Microbiome in Ageing and Its Relationship with Age-Related Diseases: A Review of the Current Literature.

Ageing is inevitable in all living organisms and is associated with physical deterioration, disease and eventually death. Dysbiosis, which is the alteration of the gut microbiome, occurs in individuals during ageing, and plenty of studies support that gut dysbiosis is responsible for the progression of different types of age-related diseases. The economic burden of age-linked health issues increases as ageing populations increase. Hence, an improvement in disease prevention or therapeutic approaches is urgently required. In recent years, vitamin E has garnered significant attention as a promising therapeutic approach for delaying the ageing process and potentially impeding the development of age-related disease. Nevertheless, more research is still required to understand how vitamin E affects the gut microbiome and how it relates to age-related diseases. Therefore, we gathered and summarized recent papers in this review that addressed the impact of the gut microbiome on age-related disease, the effect of vitamin E on age-related disease along with the role of vitamin E on the gut microbiome and the relationship with age-related diseases which are caused by ageing. Based on the studies reported, different bacteria brought on various age-related diseases with either increased or decreased relative abundances. Some studies have also reported the positive effects of vitamin E on the gut microbiome as beneficial bacteria and metabolites increase with vitamin E supplementation. This demonstrates how vitamin E is vital as it affects the gut microbiome positively to delay ageing and the progression of age-related diseases. The findings discussed in this review will provide a simplified yet deeper understanding for researchers studying ageing, the gut microbiome and age-related diseases, allowing them to develop new preclinical and clinical studies.

The Impact of Carvedilol on Organ Index, Inflammatory Mediators, Oxidative Stress Parameters and Skin Markers in D-Galactose-Induced Aging Mice

Background: Aging processes are defined as those that increase the susceptibility of individuals, as they grow older, to the factors that eventually lead to death. It is a complex multi-factorial process where several factors may interact simultaneously and may operate at many levels of functional organization.. Accumulating evidence has suggested that active ingredients that possess antioxidative and anti-inflammatory proprties could decrease the incidence and development of aging-related diseases and promote longevity. Carvedilol is a non-selective third generation β-blocker/α1-blocker with antioxidant and inflammatory activity to evaluate its antiaging effect and to investigate if it is better to given carvedilol with aging induction or after aging induction is established. Aim: To evaluate the effect of carvedilol on organ index, inflammatory mediators, oxidative stress parameters and skin markers in d-galactose-induced aging mice. Method: Male (swiss albino mice) weighing 20 to 30 g and aged 3 to 6 months was randomly divided into six groups , each consisting of 10 animals (60 mice in total). Group I was given normal saline orally only for six weeks, group II was given d-galactose 500 mg/kg orally only for six weeks, group III was given d-galactose 500 mg/kg orally and vitamin C 100 mg/kg orally concomitantly for six weeks, group IV given d-galactose 500 mg/kg orally only for six weeks, then directly next day after ending of aging induction, vitamin c 100 mg/kg started for another six weeks, group V given d-galactose 500 mg/kg orally and carvedilol 10 mg/kg orally concomitantly for six weeks, group VI given d-galactose 500 mg/kg orally only for six weeks, then directly next day after ending of aging induction, carvedilol 10 mg/kg started for another six weeks. After that, animals were weighed, euthanized, and dissected, the heart was removed and the organ index was calculated. Also the heart tissue is divided in to two parts, one homogenated to measure interleukin-Iβ, tumor necrosis factor-alpha, glutathione peroxidase and malondialdehyde, while the other piece for histopathological analysis to determine the presence of hypertrophy. Skin tissue was taken and homogenated for ELISA assay (measurement of collagen I and III levels ). Results: Results showed a significant decrease in heart organ index in animals that received carvedilol orally administered compared to aged group, with a substantial decrease in inflammatory mediators, malondialdehyde level and a marked increase in glutathione peroxidase level, collagen I and collagen III levels. Furthermore, carvedilol reverses the myocardial hypertrophy induced by D-galactose. Conclusion: The present study suggests that carvedilol has a positive antiaging benefit in reducing oxidative stress, decreasing inflammatory and skin aging markers and improving hypertrophic cardiac cells. Regarding the timing of drug administration, although carvedilol shows a benficial continuing impact when given with and after the initiation of aging. It’s better to give at starting of the aging process to control the aging series as soon as possible

The Aging of Cells: Cellular Senescence and Implications for Age-Related Diseases

Cellular senescence, the aging of cells, is a multifaceted process characterized by the progressive accumulation of molecular and cellular changes. Senescent cells, marked by their proinflammatory secretome called the senescence-associated secretory phenotype (SASP), contribute to tissue dysfunction and promote aging processes. In this review, we provide a comprehensive overview of the current understanding of cellular senescence, with a particular focus on the underlying mechanisms driving cell aging and the strategies of targeting senescent cells to extend healthspan and alleviate age-related diseases. We discuss how factors such as telomere shortening, DNA damage, oxidative stress, and oncogene activation contribute to cellular aging and the development of age-related diseases. Furthermore, we explore the potential senotherapeutic interventions, including senolytic and senomorphic therapies, that target senescent cells. Lastly, we highlight the opportunities and challenges of senotherapeutics in the context of aging and aging-associated diseases, underscoring their potential implications for human health and longevity.

Immunomodulatory Effects of SGLT2 Inhibitors-Targeting Inflammation and Oxidative Stress in Aging.

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.

Retinal microvascular complexity as a putative biomarker of biological age: a pilot study.

Physiological changes associated with aging increase the risk for the development of age-related diseases. This increase is non-specific to the type of age-related disease, although each disease develops through a unique pathophysiologic mechanism. People who age at a faster rate develop age-related diseases earlier in their life. They have an older "biological age" compared to their "chronological age". Early detection of individuals with accelerated aging would allow timely intervention to postpone the onset of age-related diseases. This would increase their life expectancy and their length of good quality life. The goal of this study was to investigate whether retinal microvascular complexity could be used as a biomarker of biological age. Retinal images of 68 participants ages ranging from 19 to 82years were collected in an observational cross-sectional study. Twenty of the old participants had age-related diseases such as hypertension, type 2 diabetes, and/or Alzheimer's dementia. The rest of the participants were healthy. Retinal images were captured by a hand-held, non-mydriatic fundus camera and quantification of the microvascular complexity was performed by using Sholl's, box-counting fractal, and lacunarity analysis. In the healthy subjects, increasing chronological age was associated with lower retinal microvascular complexity measured by Sholl's analysis. Decreased box-counting fractal dimension was present in old patients, and this decrease was 2.1 times faster in participants who had age-related diseases (p = 0.047). Retinal microvascular complexity could be a promising new biomarker of biological age. The data from this study is the first of this kind collected in Montenegro. It is freely available for use.

Urolithin A as a Potential Agent for Prevention of Age-Related Disease: A Scoping Review.

The aging of an organism is hallmarked by systemic loss of functional tissue, resulting in increased fragility and eventual development of age-related neurodegenerative, musculoskeletal, cardiovascular, and neoplastic diseases. Growing scientific evidence points to mitochondrial dysfunction as a key contributor in the aging process and subsequent development of age-related pathologies. Under normal physiologic conditions, the body removes dysfunctional mitochondria via an autophagic process known as mitophagy. Urolithin A (UA), a metabolite produced when gut microflora digests the polyphenol compounds ellagitannin and ellagic acid, is a known inducer of mitophagy via several identified mechanisms of action. The primary objective of this scoping review is to identify and summarize the clinical relevance of UA supplementation in the prevention of age-related pathology and diseases. A computer-assisted literature review was performed using PubMed and EMBASE for primary source research articles examining UA supplementation and aging-related pathologies. A total of 293 articles were initially identified from a database search, and 15 articles remained for inclusion in this review, based on predetermined criteria. Analysis of the 15 identified publications demonstrated that UA holds potential as a dietary intervention for slowing the progression of aging and preventing the development of age-related disease. This review also illustrates the potential role that mitochondrial health and inflammation play in the progression of age-related pathology. Identifying the clinical relevance of UA supplementation in the prevention of age-related pathology and diseases will help further the focus of research on treatments that may improve the longevity and quality of life in patientsat risk for these comorbidities.

Towards disease-oriented dosing of rapamycin for longevity: does aging exist or only age-related diseases?

Both individuals taking rapamycin, an anti-aging drug, and those not taking it will ultimately succumb to age-related diseases. However, the former, if administered disease-oriented dosages for a long time, may experience a delayed onset of such diseases and live longer. The goal is to delay a particular disease that is expected to be life-limiting in a particular person. Age-related diseases, quasi-programmed during development, progress at varying rates in different individuals. Rapamycin is a prophylactic anti-aging drug that decelerates early development of age-related diseases. I further discuss hyperfunction theory of quasi-programmed diseases, which challenges the need for the traditional concept of aging itself.