Increased Life Span Research Articles

DWORF Extends Life Span in a PLN-R14del Cardiomyopathy Mouse Model by Reducing Abnormal Sarcoplasmic Reticulum Clusters.

The p.Arg14del variant of the PLN (phospholamban) gene causes cardiomyopathy, leading to severe heart failure. Calcium handling defects and perinuclear PLN aggregation have both been suggested as pathological drivers of this disease. Dwarf open reading frame (DWORF) has been shown to counteract PLN regulatory calcium handling function in the sarco/endoplasmic reticulum (S/ER). Here, we investigated the potential disease-modulating action of DWORF in this cardiomyopathy and its effects on calcium handling and PLN aggregation. We studied a PLN-R14del mouse model, which develops cardiomyopathy with similar characteristics as human patients, and explored whether cardiac DWORF overexpression could delay cardiac deterioration. To this end, R14Δ/Δ (homozygous PLN-R14del) mice carrying the DWORF transgene (R14Δ/ΔDWORFTg [R14Δ/Δ mice carrying the DWORF transgene]) were used. DWORF expression was suppressed in hearts of R14Δ/Δ mice with severe heart failure. Restoration of DWORF expression in R14Δ/Δ mice delayed cardiac fibrosis and heart failure and increased life span >2-fold (from 8 to 18 weeks). DWORF accelerated sarcoplasmic reticulum calcium reuptake and relaxation in isolated cardiomyocytes with wild-type PLN, but in R14Δ/Δ cardiomyocytes, sarcoplasmic reticulum calcium reuptake and relaxation were already enhanced, and no differences were detected between R14Δ/Δ and R14Δ/ΔDWORFTg. Rather, DWORF overexpression delayed the appearance and formation of large pathogenic perinuclear PLN clusters. Careful examination revealed colocalization of sarcoplasmic reticulum markers with these PLN clusters in both R14Δ/Δ mice and human p.Arg14del PLN heart tissue, and hence these previously termed aggregates are comprised of abnormal organized S/ER. This abnormal S/ER organization in PLN-R14del cardiomyopathy contributes to cardiomyocyte cell loss and replacement fibrosis, consequently resulting in cardiac dysfunction. Disorganized S/ER is a major characteristic of PLN-R14del cardiomyopathy in humans and mice and results in cardiomyocyte death. DWORF overexpression delayed PLN-R14del cardiomyopathy progression and extended life span in R14Δ/Δ mice, by reducing abnormal S/ER clusters.

Investigating Human Expectancy by Linear Regression

In recent years, many people have studied the human lifespan, some people study how to extend the human lifespan, explore the limits of the human lifespan, and so on. But what are the factors that affect human lifespan, and will they lead to an increase or decrease in lifespan? This paper was analyzed by using linear regression, where specific analyses were performed using R- square and multiple R, mainly studies the influence of three factors, BMI, Schooling, and HIV/AIDS, on human life expectancy between developing and developed countries through linear regression methods.

Secrecy Energy Efficiency Maximization for Secure Unmanned-Aerial-Vehicle-Assisted Simultaneous Wireless Information and Power Transfer Systems

Unmanned aerial vehicle (UAV)-assisted simultaneous wireless information and power transfer (SWIPT) systems have recently gained significant attraction in internet-of-things (IoT) applications that have limited or no infrastructure. Specifically, the free mobility of UAVs in three-dimensional (3D) space allows us good-quality channel links, thereby enhancing the communication environment and improving performance in terms of achievable rates, latency, and energy efficiency. Meanwhile, IoT devices can extend their battery life by harvesting the energy following the SWIPT protocol, which leads to an increase in the overall system lifespan. In this paper, we propose a secure UAV-assisted SWIPT system designed to optimize the secrecy energy efficiency (SEE) of a ground network, wherein a base station (BS) transmits confidential messages to an energy-constrained device in the presence of a passive eavesdropper. Here, we employ a UAV acting as a helper node to improve the SEE of the system and to aid in the energy harvesting (EH) of the battery-limited ground device following the SWIPT protocol. To this end, we formulate the SEE maximization problem by jointly optimizing the transmit powers of the BS and UAV, the power-splitting ratio for EH operations, and the UAV’s flight path. The solution is obtained via a proposed algorithm that leverages successive convex approximation (SCA) and Dinkelbach’s method. Through simulations, we corroborate the feasibility and effectiveness of the proposed algorithm compared to conventional partial optimization approaches.

CONVERGENCE STRATEGY OF DIGITAL LIVESTOCK PRODUCTION AND ANIMAL BIOMODELS FOR HUMAN WELLNESS IN FUTURE: A REVIEW

As human lifespan increase, interest in human health and the digital livestock system is also increasing. Therefore, it is necessary to converge the digital livestock system and animal biomodels. In the fourth industrial revolution, animal biomodels and the digital livestock system as algorithms in agriculture are emerging rapid evolution by converging enovation technologies in fields of bio-healthcare, biomedical research, and life science. Animal biomodels have been used as important foundational tools to transit screening processes and clinical trials for useful substances and potential drugs in human and animal life science. Animal biomodels for studying human and animal diseases have enabled medical innovation and derived numerous outcomes such as vaccines. It is very important to choose appropriate animal biomodels in clinical studies. When selecting experimental animals for human and animal diseases, some parameters should be kept in mind. Convergence of the digital livestock system with animal biomodel can help us greatly solve human and animal health diseases and welfare issues. It enables prevention of human diseases and vaccine development for emerging infectious diseases by applying appropriate animal biomodels, thus contributing to the development of bio-healthcare industry. Animal biomodels are in vivo models for determining mechanisms of life phenomena and diseases progression. They can also be used to evaluate the safety, effectiveness, new cosmetic materials, and action mechanisms of functional materials and foods. Animal experiments using animal biomodels must be based on ethical considerations. Animal biomodels can be produced through drugs, diet, surgical procedures, spontaneous mutation, crossbreeding, biotechnology such as transformation and genetic manipulation, and so on. In this paper, preemptive response strategies for the development of livestock and biomedical industry of the future are reviewed through understanding the importance of animal biomodels and the digital livestock system as agriculture algorithms. Animal models for studying mechanisms of diseases in human, livestock, and birds, in ovo technology for poultry, preparation theories, animal bioethics, and practical cases are also explained. Keywords: Digital livestock system, biomodels, clinical trial, animal bioehtics, agriculture algorithms

Age Is Just a Number: Progress and Obstacles in the Discovery of New Candidate Drugs for Sarcopenia.

Sarcopenia is a disease characterized by the progressive loss of skeletal muscle mass and function that occurs with aging. The progression of sarcopenia is correlated with the onset of physical disability, the inability to live independently, and increased mortality. Due to global increases in lifespan and demographic aging in developed countries, sarcopenia has become a major socioeconomic burden. Clinical therapies for sarcopenia are based on physical therapy and nutritional support, although these may suffer from low adherence and variable outcomes. There are currently no clinically approved drugs for sarcopenia. Consequently, there is a large amount of pre-clinical research focusing on discovering new candidate drugs and novel targets. In this review, recent progress in this research will be discussed, along with the challenges that may preclude successful translational research in the clinic. The types of drugs examined include mitochondria-targeting compounds, anti-diabetes agents, small molecules that target non-coding RNAs, protein therapeutics, natural products, and repositioning candidates. In light of the large number of drugs and targets being reported, it can be envisioned that clinically approved pharmaceuticals to prevent the progression or even mitigate sarcopenia may be within reach.

MALT-1 shortens lifespan by inhibiting autophagy in the intestine of C. elegans.

The caspase-like protease MALT1 promotes immune responses and oncogenesis in mammals by activating the transcription factor NF-κB. MALT1 is remarkably conserved from mammals to simple metazoans devoid of NF-κB homologs, like the nematode C. elegans. To discover more ancient, NF-κB -independent MALT1 functions, we analysed the phenotype of C. elegans upon silencing of MALT-1 expression systemically or in a tissue-specific manner. MALT-1 silencing in the intestine caused a significant increase in life span, whereas intestinal overexpression of MALT-1 shortened life expectancy. Interestingly, MALT-1-deficient animals showed higher constitutive levels of autophagy in the intestine, which were particularly evident in aged or starved nematodes. Silencing of the autophagy regulators ATG-13, BEC-1 or LGG-2, but not the TOR homolog LET-363, reversed lifespan extension caused by MALT-1 deficiency. These findings suggest that MALT-1 limits the lifespan of C. elegans by acting as an inhibitor of an early step of autophagy in the intestine.

Genetics of human longevity: From variants to genes to pathways.

The current increase in lifespan without an equivalent increase in healthspan poses a grave challenge to the healthcare system and a severe burden on society. However, some individuals seem to be able to live a long and healthy life without the occurrence of major debilitating chronic diseases, and part of this trait seems to be hidden in their genome. In this review, we discuss the findings from studies on the genetic component of human longevity and the main challenges accompanying these studies. We subsequently focus on results from genetic studies in model organisms and comparative genomic approaches to highlight the most important conserved longevity-associated pathways. By combining the results from studies using these different approaches, we conclude that only five main pathways have been consistently linked to longevity, namely (1) insulin/insulin-like growth factor 1 signalling, (2) DNA-damage response and repair, (3) immune function, (4) cholesterol metabolism and (5) telomere maintenance. As our current approaches to study the relevance of these pathways in humans are limited, we suggest that future studies on the genetics of human longevity should focus on the identification and functional characterization of rare genetic variants in genes involved in these pathways.

Influence of the Rate of Changes in the COX1 Gene on Body Size and Sexual Selection in Carp Hybridization

The influence of mtDNA cytochrome c-oxidase I gene fragment variability on body length was studied in twelve species of cyprinids, which may have hybrids with Rutilus rutilus L. and Abramis brama L., and in reciprocal hybrids (RA, AR) and alloplasmatic backcrosses (ARR, RAA) of roach (R) and bream (A). It has been established that the rate of nucleotide substitutions in COX1 is negatively related not only to body size but also to fish life span, which differentiates them into two groups: group I – species with a high rate of COX1 changes and a relatively small body size and group II – species with low sequence variability and relatively large body size. The boundary for the distinguished groups runs between species the same genus Leuciscus leuciscus and L. idus: with a twofold decrease in the rate of substitutions in ide, a twofold increase in body size and lifespan occurs, which indicates a decrease in the rate of cellular respiration and free radical leak, and the exact mitonuclear match respiratory complexes. Presumably, the decrease in the rate of COX1 changes in species of group II and in bleak Alburnus alburnus is associated with an increase in the size of genome, which provides additional protection of genes from chemical mutagens and, regardless of body size, reduces the rate of aerobic metabolism. It has been experimentally shown that mtDNA affects body length. When bream mtDNA is included in the roach nuclear genome, ARR backcrosses have the body length of a bream and high viability, while RAA backcrosses with roach mtDNA and the bream nuclear genome inherit the roach body length and reduce viability. Species of group II are not able to effectively use the highly polymorphic mtDNA of species of group I, which is also manifested by a violation of the inheritance of a longer bream body length in RA hybrids and leads to reproductive isolation. Group I species, such as Rutilus rutilus, can include mtDNA of both groups in their genome, which underlies sexual selection in hybridization. Accordingly, sexual size dimorphism has a genetic origin, and body size for a potential partner can be a signal for determining the mitonuclear compatibility of genomes in respiratory complexes.

The Negative Impact of Insulin Resistance/Hyperinsulinemia on Chronic Heart Failure and the Potential Benefits of Its Screening and Treatment.

This opinion article highlights the potential alterations caused by insulin resistance and hyperinsulinemia on the cardiovascular system and their negative impact on heart failure (HF), and describes the potential benefits of an early screening with consequent prompt treatment. HF is the final event of several different cardiovascular diseases. Its incidence has been increasing over the last decades because of increased survival from ischemic heart disease thanks to improvements in its treatment (including myocardial revascularization interventions) and the increase in life span. In particular, incidence of HF with preserved ejection fraction (HFpEF) is significantly increasing, and patients with HFpEF often are also affected by diabetes mellitus and insulin resistance (IR), with a prevalence > 45%. Concentric left ventricular (LV) remodeling and diastolic dysfunction are the main structural abnormalities that characterize HFpEF. It is well documented in the literature that IR with chronic hyperinsulinemia, besides causing type 2 diabetes mellitus, can cause numerous cardiovascular alterations, including endothelial dysfunction and increased wall thicknesses of the left ventricle with concentric remodeling and diastolic dysfunction. Therefore, it is conceivable that IR might play a major role in the pathophysiology and the progressive worsening of HF. To date, several substances have been shown to reduce IR/hyperinsulinemia and have beneficial clinical effects in patients with HF, including SGLT2 inhibitors, metformin, and berberine. For this reason, an early screening of IR could be advisable in subjects at risk and in patients with heart failure, to promptly intervene with appropriate therapy. Future studies aimed at comparing the efficacy of the substances used both alone and in association are needed.

Adult sex ratios affect mating behaviour in the common housefly Musca domestica L. (Diptera; Muscidae)

Abstract Adult sex ratio determines the level of mate availability and intrasexual competition for each sex. Sex ratio biases have been proposed to enhance the productivity of animal rearing procedures. However, behaviour may change in response to sex ratio manipulations that may counteract potential benefits. We investigated how sex ratios affected mating behaviour of the housefly Musca domestica, a species used in the animal feed industry. We hypothesized a reduced courtship effort and mating latency and increased ejaculate allocation (copulation duration) under male-biased sex ratios, whereas female-biased sex ratios would lead to the opposite effects. However, courtship effort was reduced in female-biased groups, implying reduced male harassment. Mating latency was lower and copulation lasted longer in female-biased groups, which may reduce reproduction time and increase female fecundity and lifespan. Our results indicate that in houseflies, female-biased sex ratios cause behavioural changes in both sexes that could positively contribute to reproductive output.

CMS121 Partially Attenuates Disease Progression in Mouse Models of Huntington's Disease.

There are currently no drugs that meaningfully slow down the progression of Huntington's disease (HD). Moreover, drug candidates against a single molecular target have not had significant success. Therefore, a different approach to HD drug discovery is needed. Previously we showed that the flavonol fisetin is efficacious in mouse and fly models of HD (Hum. Mol. Gen. 20:261, 2011). It is also effective in animal models of Alzheimer's disease (AD), ischemic stroke, and the CNS complications of diabetes, all of which share some pathological features with HD. Potent derivatives of fisetin with improved pharmacology were made that maintain its multiple biological activities (J. Med. Chem. 55:378, 2012). From 160 synthetic fisetin derivatives, one, CMS121, was selected for further study in the context of HD based on pharmacological parameters and its efficacy in animal models of AD. Both R6/2 and YAC128 mouse models of HD were used in these studies. We examined motor function using multiple assays as well as survival. In the R6/2 mice, we also looked at the effects of CMS121 on striatal gene expression. In both models, we found a slowing of motor dysfunction and an increase in median life span. Interestingly, in the YAC128 mice, the effects on the slowing in motor function loss became increasingly more pronounced as the mice aged. CMS121 also reduced HD-driven changes in the expression of genes associated with the proteasome and oxidative phosphorylation. Overall, these results suggest that CMS121 could provide some benefits for HD patients, particularly with regard to increasing health span.

Circulating neutrophils from patients with early breast cancer have distinct subtype-dependent phenotypes

PurposeAn elevated number of circulating neutrophils is a poor prognostic factor for breast cancer, where evidence of bone marrow cancer-dependent priming is found. However, how early this priming is detectable remains unclear.Patients and methodsHere, we investigate changes in circulating neutrophils from newly diagnosed breast cancer patients before any therapeutic interventions. To do this, we assessed their lifespan and their broader intracellular kinase network activation states by using the Pamgene Kinome assay which measures the activity of neutrophil kinases.ResultsWe found sub-type specific L-selectin (CD62L) changes in circulating neutrophils as well as perturbations in their overall global kinase activity. Strikingly, breast cancer patients of different subtypes (HR+, HER2+, triple negative) exhibited distinct neutrophil kinase activity patterns indicating that quantifiable perturbations can be detected in circulating neutrophils from early breast cancer patients, that are sensitive to both hormonal and HER-2 status. We also detected an increase in neutrophils lifespan in cancer patients, independently of tumour subtype.ConclusionsOur results suggest that the tumour-specific kinase activation patterns in circulating neutrophils may be used in conjunction with other markers to identify patients with cancer from those harbouring only benign lesions of the breast. Given the important role neutrophil in breast cancer progression, the significance of this sub-type of specific priming warrants further investigation.

Metformin potentiates nephrotoxicity by promoting NETosis in response to renal ferroptosis

Given the rapidly aging population, aging-related diseases are becoming an excessive burden on the global healthcare system. Metformin has been shown to be beneficial to many age-related disorders, as well as increase lifespan in preclinical animal models. During the aging process, kidney function progressively declines. Currently, whether and how metformin protects the kidney remains unclear. In this study, among longevity drugs, including metformin, nicotinamide, resveratrol, rapamycin, and senolytics, we unexpectedly found that metformin, even at low doses, exacerbated experimentally-induced acute kidney injury (AKI) and increased mortality in mice. By single-cell transcriptomics analysis, we found that death of renal parenchymal cells together with an expansion of neutrophils occurs upon metformin treatment after AKI. We identified programmed cell death by ferroptosis in renal parenchymal cells and blocking ferroptosis, or depleting neutrophils protects against metformin-induced nephrotoxicity. Mechanistically, upon induction of AKI, ferroptosis in renal parenchymal cells initiates the migration of neutrophils to the site of injury via the surface receptor CXCR4–bound to metformin–iron–NGAL complex, which results in NETosis aggravated AKI. Finally, we demonstrated that reducing iron showed protective effects on kidney injury, which supports the notion that iron plays an important role in metformin-triggered AKI. Taken together, these findings delineate a novel mechanism underlying metformin-aggravated nephropathy and highlight the mechanistic relationship between iron, ferroptosis, and NETosis in the resulting AKI.

Energy-economic and exergy-environment performance evaluation of solar energy integrated essential oil extraction system

Solar Steam distillation system (SSDS) for essential oil extraction from medicinal plants is developed and analysed based on energy, exergy, economic, exergoeconomic, environmental and enviroeconomic point of view. System is analysed for various batch sizes of two different medicinal plants (Peppermint and Eucalyptus) and compared. Maximum and minimum system efficiency is calculated as 48.68 % and 43.25 % for 2 kg of peppermint and 6 kg of eucalyptus, respectively, whereas highest and lowest exergy efficiency of system is 27.96 % and 22.50 % for 6 kg and 4 kg of eucalyptus leaves, respectively. Estimated return on investment (ROI), internal rate of return (IRR) and payback period (PBP) of SSDS producing 72 L of peppermint oil per year were 14.03 %, 18.77 % and 5.67 years, respectively over the projected economic life span of 25 years. 11.43 and 19.94 % with increase in lifespan of system by 5 enhanced exergoeconomic parameters for peppermint oil and 10 years, respectively at same interest rate of 5 % while 11.30 and 19.90 %, respectively increase the corresponding values for eucalyptus oil. CO2 mitigated over the lifespan from SSDS for peppermint oil and eucalyptus oil based on energy approach is found as 2.37, 4.74, 7.11 tons CO2 and 1.97, 3.95, 5.9 tons CO2 for 2, 4 and 6 kg batch size, respectively. Whereas, the corresponding values based on exergy approach are 0.15, 0.11, 0.14 tons CO2 and 0.12, 0.09, 0.12 tons CO2, respectively.

In vitro and in vivo anticancer activity of mebendazole in colon cancer: a promising drug repositioning.

Colon cancer is one of the most common cancers and one of the main causes of death worldwide. Therefore, new treatment methods with better efficiency and fewer risks are very necessary. Mebendazole (MBZ), a drug commonly used for helminthic infections, has recently received attention as a suitable candidate for the treatment of various cancers. This study aimed to investigate, in vitro and in vivo, anticancer activity and selectivity Index of MBZ on colon cancer. HT-29 (human colorectal adenocarcinoma) and MCF-10 (non-tumorigenic epithelial) cell lines were treated with MBZ and Doxorubicin (DOX; positive control drug). IC50 values were estimated using methyl thiazole diphenyl-tetrazolium bromide (MTT) assay. We employed flow cytometry using annexin V-FITC and propidium iodide dyes. For the animal study, colon cancer was subcutaneously induced by CT26 cells (mouse colon cancer) in Bulb/C mice. The mice were treated with 0.05 of LD50, intraperitoneal, every other day for 35 days. Finally, the survival rate, tumor volume, and tumor weight were calculated. Our results demonstrated that IC50 values after 72 h for HT29 and MCF-10 cell lines were 0.29 ± 0.04 µM and 0.80 ± 0.02 µM, respectively. MBZ was more selective than DOX in inhibiting the proliferation of cancer cells compared to normal cells (2. 75 vs. 2.45). Annexin V/PI staining demonstrated that MBZ treatment at IC50 concentrations induced (78 ± 12%) apoptosis in the HT29 cancer cell line after 48 h (P ≤ 0.0001). Also, in mice bearing colon cancer, MBZ significantly reduced the tumor volume (1177 ± 1109 mm3; P ≤ 0.001) and tumor weight (2.30 ± 1.97 g; P ≤ 0.0001) compared to the negative control group (weight 12.45 ± 2.0 g; volume 7346 ± 1077). Also, MBZ increases mean survival time (MST) and increase life span (ILS) percentage in the animal study (51.2 ± 37% vs 93%, respectively). This study suggests that mebendazole strongly and selectively inhibits proliferation and induces apoptosis in colon cancer cells. It may be, accordingly, a promising drug for clinical research and application.

Wear Resistance Study of Bionic Pitted Ni Cladding Layer on 7075 Aluminum Alloy Drill Pipe Surface

To enhance the lifespan of drill pipes and minimize wear, this study introduces a bionic structure model inspired by the pit shape structure found in the dung beetle’s abdomen. The stress distribution and wear of bionic pitted structure and ordinary structure are simulated by finite element software. The findings revealed that the bionic structure significantly improves stress distribution, resulting in an impressive 81.3% increase in lifespan. Subsequently, the surface of the 7075 aluminum drill pipe was coated with Ni powder by a laser cladding system. Wear tests were conducted to analyze the wear and surface damage behavior of the cladding layer. The microstructure, composition, and microhardness of the cladding layer were measured and observed. The results showed that the cladding layer was mainly composed of Al3Ni2 and had high hardness. Additionally, a transition region exists between the cladding layer and the substrate, comprising relatively low hardness Al, thereby enhancing the drill pipe’s ability to withstand alternating loads. Furthermore, the bionic structure possesses the capability to store particles, effectively reducing the occurrence of abrasive wear and increasing the lifespan by 70.0%.

SAT671 SGLT2 Inhibition Decreases Adipose Tissue And Global Inflammaging Profile Of Older Obese Adults With Pre-Diabetes

Abstract Disclosure: J. Nie: None. M.K. Semwal: None. F.M. Acosta: None. A.R. Stepanenko: None. M. Brown: None. A.J. Moody: None. N. Sanchez: None. T.M. Cortes: None. Y. Qin: None. C. Triplitt: None. G. Clarke: None. S.E. Espinoza: None. N. Musi: None. C. Solis-Herrera: None. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are drugs for treating T2D. Through their glucosuric effect, you see a reduced HbA1c, weight loss, and improved insulin sensitivity/ β-cell function. Beyond their glycemic properties, SGLT2i provide substantial cardio-renal benefits. Given their multiple therapeutic advantages and established safety profile, there is the presupposition that SGLT2i may have various beneficial possibilities in medical practice. An area of interest for SGLT2i is their use as agents for late-aging and longevity. SGLT2i are known to promote a calorie restriction (CR) state by promoting glucosuria and fatty acid-oxidation/ketogenesis and reducing insulin levels. CR activates a myriad of anti-aging-related pathways, including senescence-associated “inflammaging,” which can be triggered by obesity and states of overnutrition. However, clinical research in this area remains largely unexplored. A single-center, open-label, randomized-controlled clinical trial was designed to determine the effect of SGLT2i on the aging-related processes of global and adipose tissue inflammation and senescence. Twenty older, obese, pre-diabetic subjects (Age=70±1.5, BMI=33.7±0.6, A1c=5.9±0.03) were randomized dapagliflozin 10mg/day (SGLT2i) vs. nutritional counseling for weight loss (control) in a 1:1 fashion for 12 weeks. Healthspan and clinical evaluation were performed at baseline and weeks 10-12 of the study. The SGLT2i group showed a significant decrease (-5.4±1.7, p=0.01) in weight loss, downward trend in HbA1c (-0.02±0.06 vs. +0.06±0.04), and significant loss in %Fat vs. control (-1%, p=0.05 vs. -0.5%, p=0.1). Given adiposity changes observed with SGLT2i, in a subset of subjects (n=10), subcutaneous fat biopsies were performed, and single nuclei (sn)RNA-seq done to map changes in adipose cellular populations (mature adipocytes, immune, endothelial, and adipogenic progenitor cells) and molecular profiling. Notably, with SGLT2i, the mature adipocyte, immune, and adipogenic progenitor cells, saw a significant (p≤0.05) decrease in senescent score. Globally, plasma-measured inflammaging-associated factors in the IL8 and TNFα families, also saw a significant decrease (p≤0.05) with SGLT2i.Aging and metabolic homeostasis are bidirectional processes. As you age, adiposity tends to increase, associated with an upsurge in the development of metabolic syndrome-related diseases in older adults. Here we demonstrate that in the high-risk population of older obese adults with pre-diabetes, SGLT2i targets multiple points in the spectrum that delay the aging process. In particular, we show evidence that SGLT2i treatment improves the global and adipose senescent and inflammatory profile, alongside glycemic and weight control. These findings support the notion that SGLT2i may contribute to the increase of both healthspan and lifespan. Presentation: Saturday, June 17, 2023

Hybrid deep learning and metaheuristic model based stroke diagnosis system using electroencephalogram (EEG)

Over the last few decades, there has been a significant increase in the average lifespan. Consequently, the number of elderly people suffering from strokes has also risen. As a result, strokes and their treatments have become crucial subjects of research, particularly for the application of machine learning. One of the primary factors in stroke treatment is the speed of response. Currently, both computed tomography (CT) and magnetic resonance imaging (MRI) are used to diagnose strokes. However, CT takes eight hours before an accurate diagnosis can be made, and MRI is expensive and not available in all hospitals. Therefore, there is a growing need for novel approaches to identifying strokes based on electroencephalogram (EEG) signals. In this paper, a hybrid model of deep learning and metaheuristic was developed in the offline stage to classify strokes. Since EEG data is a time series with frequencies, a hybrid model was deemed appropriate. This hybrid model combined a Convolutional Neural Network (CNN) with bidirectional Gated Recurrent Unit (BiGRU). The performance of this model surpassed that of other comparable models. Given the paramount importance of speed and accuracy in this work, the harmony search (HS) algorithm, which is specialized in handling frequencies, was used for feature selection. HS outperformed all similar algorithms when applied to the CNN-BiGRU hybrid model. Additionally, for the optimization of continuous hyperparameters, the multiverse optimization (MVO) algorithm was employed, which proved to be the most effective when compared to another similar algorithm for validation purposes. The new model, CNN-BiGRU-HS-MVO, was applied to analyze the data collected from Al Bashir Hospital using the MUSE-2 portable device, resulting in an impressive prediction accuracy of 99.991%. Moreover, it demonstrated an 11.08% improvement over the results from the paper titled “Predicting stroke severity with a 3-min recording from the Muse portable EEG study”. Furthermore, a decision support system was built on the cloud computing environment based on the hybrid model. This system allows for the diagnosis of patients anytime and from anywhere within minutes, with the authorized person receiving the diagnosis results through SMS notification.

Altitudinal Patterns of Foliar Nutrients in Dominant Tree Species: Are Central Himalayan Forests Nutrient Stressed?

In forest ecosystems nutrient availability is one of the most important drivers of tree growth and ecosystem function. We studied changes in soil and foliar nutrients (N, P & K) and leaf N and P stoichiometry in eight dominant canopy and sub-canopy forest tree species of Central Himalayan forests occurring between 300 and 2200 m asl. Nutrient (N, P & K) concentration in leaves at bud break, mature and senescent stage varied significantly across the tree species. The nutrient resorption efficiency (NRE) varied significantly across the species and found ranging for N from 48.7 - 76.8%. Both the nitrogen resorption efficiency (NRE) and phosphorus resorption efficiency (PRE) increased linearly with altitude (R2= 0.647 for NRE significant at p< 0.05; and R2 for PRE= 0.525; NS) pointing out that trees growing in temperate climate conserve nutrients more efficiently to withstand the slow mineralization due to cold climate. With the increasing altitude leaf life-span increases significantly (R2= 0.0025; p< 0.0074). ANOVA indicates that the foliar N and P and altitude were unrelated. The low N: P ratio, a measure of nutrient status of forest ecosystems at senescent leaf stage, found ranging from 9.97 in Q. floribunda to 18.8 in P. roxburghii points out that forests of the study region are nutrient stressed, partly due to low P mineralization in temperate climate, leaching of nutrients due to heavy monsoon rain, and poorly developed underlying geology. Thus, the Central Himalayan forests are characterized by high NRE and low growth rate with increasing altitude. Winter season warming might help improve the nutrient availability in the forest floor and nutrient uptake to enhance nutrient cycling and biomass productivity in these forests.

The role of immune aging in Giant Cell Arteritis

Giant cell arteritis (GCA) is a granulomatous vasculitis with a predilection for medium and large calibre arteries. The most significant risk factor for its development is advancing age, with a peak incidence in the seventh and eighth decades of life. Despite this, until recently, the role of aging in disease pathogenesis has been largely overlooked. Advancing age is associated with numerous alterations in both the innate and adaptive immune system. Indeed, there is significant overlap in the cellular and molecular pathways involved in immune aging and those observed in the pathogenesis of GCA. In this review we explore these similarities and further expand the discussion on the postulated role of accelerated immune ageing in the pathogenesis of GCA. With the dramatic increase in lifespan in recent decades, elucidating the potential role of early immune aging in disease pathogenesis is extremely pertinent, with the potential to offer a new therapeutic avenue not only for those with GCA, but all immune mediated rheumatic diseases.