Decline In Physiological Function Research Articles

A simple framework to distinguish 'individualistic' from a 'uniform rate' of ageing within or between study populations.

Ageing is accompanied by a progressive decline in physiological functions. It is often argued that the rate of ageing differs between people and is 'highly individualistic'. This view is not unequivocally shared, and others have argued that the rate of ageing is rather 'uniform'. Distinguishing conclusively between these views requires longitudinal data, but these are difficult to obtain as they require decades of data collection from individuals. Here, a simple framework is proposed to assess in cross-sectional data whether in a given population the rate is 'highly individualistic' or rather 'uniform'. It is illustrated that an age-related decrease in the standard deviation (SD) of a certain parameter combined with a non-changing coefficient of variation (COVAR) reflects a 'uniform' rate of ageing, whilst an increase or decrease in COVAR with or without a concomitant increase in SD reflects a 'highly individualistic' rate of ageing. This framework is applied to some published data, focussing on muscle strength, power and physical function for the sake of illustration, and it is suggested that most studies do in fact show a 'highly individualistic' rate of ageing, perhaps apart from a 'uniform' rate of ageing in master athletes.

Mechanisms underlying the anti-aging activity of bergamot (Citrus bergamia) extract in human red blood cells.

Introduction: Aging is a process characterised by a decline in physiological functions. Reactive species play a crucial role in the aging rate. Due to the close relationship between aging and oxidative stress, functional foods rich in phytochemicals are excellent candidates to neutralise age-related changes. Aim: This investigation aims to verify the potential protective role of bergamot (Citrus bergamia, Femminello cultivar) peel and juice extract in a model of aging represented by human red blood cells (RBCs) exposed to D-Galactose (DGal). Methods: Bergamot peel and juice extracts were subjected to RP-HPLC/PDA/MS for determination of their composition in bioactive compounds. Markers of oxidative stress, including ROS production, thiobarbituric acid reactive substances (TBARS) levels -a marker of lipid peroxidation, oxidation of total protein sulfhydryl groups, as well as the expression and anion exchange capability of band 3 and glycated haemoglobin (A1c) production have been investigated in RBCs treated with D-Gal for 24 h, with or without pre-incubation for 15 min with 5 μg/mL peel or juice extract. In addition, the activity of the endogenous antioxidant system, including catalase (CAT) and superoxide dismutase (SOD), as well as the diversion of the RBC metabolism from glycolysis towards the pentose phosphate pathway shunt, as denoted by activation of glucose-6-phosphate dehydrogenase (G6PDH), have been explored. Results: Data shown here suggest that bergamot peel and juice extract i) prevented the D-Gal-induced ROS production, and consequently, oxidative stress injury to biological macromolecules including membrane lipids and proteins; ii) significantly restored D-Gal-induced alterations in the distribution and ion transport kinetics of band 3; iii) blunted A1c production; iv) effectively impeded the over-activation of the endogenous antioxidant enzymes CAT and SOD; and v) significantly prevented the activation of G6PDH. Discussion: These results further contribute to shed light on aging mechanisms in human RBCs and identify bergamot as a functional food rich in natural antioxidants useful for prevention and treatment of oxidative stress-related changes, which may lead to pathological states during aging.

Investigating Mitochondrial Gene Expression Patterns in Drosophila melanogaster Using Network Analysis to Understand Aging Mechanisms

The process of aging is a complex phenomenon that involves a progressive decline in physiological functions required for survival and fertility. To better understand the mechanisms underlying this process, the scientific community has utilized several tools. Among them, mitochondrial DNA has emerged as a crucial factor in biological aging, given that mitochondrial dysfunction is thought to significantly contribute to this phenomenon. Additionally, Drosophila melanogaster has proven to be a valuable model organism for studying aging due to its low cost, capacity to generate large populations, and ease of genetic manipulation and tissue dissection. Moreover, graph theory has been employed to understand the dynamic changes in gene expression patterns associated with aging and to investigate the interactions between aging and aging-related diseases. In this study, we have integrated these approaches to examine the patterns of gene co-expression in Drosophila melanogaster at various stages of development. By applying graph-theory techniques, we have identified modules of co-expressing genes, highlighting those that contain a significantly high number of mitochondrial genes. We found important mitochondrial genes involved in aging and age-related diseases in Drosophila melanogaster, including UQCR-C1, ND-B17.2, ND-20, and Pdhb. Our findings shed light on the role of mitochondrial genes in the aging process and demonstrate the utility of Drosophila melanogaster as a model organism and graph theory in aging research.

Aging-related histone modification changes in brain function.

Aging can be defined as a decline of physiological function that is more difficult to reverse, characterized by the loss of the physiological integrity of tissues, organs, and cells of an organism over time. Normal aging is associated with structural and functional changes in the brain, involving neuronal apoptosis, synaptic structure, neurotransmission, and metabolism alterations, leading to impairment in sleep, cognitive functions, memory, learning, and motor and sensory systems. Histone modification is a significant aging-related epigenetic change that influences synaptic and mitochondrial function and immune and stress responses in the brain. This review discusses the changes in histone modifications that occur during brain aging, specifically methylation and acetylation, and the associated changes in gene transcription and protein expression. We observed that genes related to synaptic and mitochondrial function are downregulated in the aging brain, while genes related to immune response and inflammatory functions are upregulated.

3D ECM-Based Scaffolds Boost Young Cell Secretome-Derived EV Rejuvenating Effects in Senescent Cells.

Aging is a complex, multifaceted degenerative process characterized by a progressive accumulation of macroscopic and microscopic modifications that cause a gradual decline of physiological functions. During the last few years, strategies to ease and counteract senescence or even rejuvenate cells and tissues were proposed. Here we investigate whether young cell secretome-derived extracellular vesicles (EVs) ameliorate the cellular and physiological hallmarks of aging in senescent cells. In addition, based on the assumption that extracellular matrix (ECM) provides biomechanical stimuli, directly influencing cell behavior, we examine whether ECM-based bio-scaffolds, obtained from decellularized ovaries of young swine, stably maintain the rejuvenated phenotype acquired by cells after exposure to young cell secretome. The results obtained demonstrate that young cells release EVs endowed with the ability to counteract aging. In addition, comparison between young and aged cell secretomes shows a significantly higher miR-200 content in EVs produced using fibroblasts isolated from young donors. The effect exerted by young cell secretome-derived EVs is transient, but can be stabilized using a young ECM microenvironment. This finding indicates a synergistic interaction occurring among molecular effectors and ECM-derived stimuli that cooperate to control a unique program, driving the cell clock. The model described in this paper may represent a useful tool to finely dissect the complex regulations and multiple biochemical and biomechanical cues driving cellular biological age.

노화의 개념, 진단 및 관리

Anti-aging medicine is defined as ‘the newest clinical specialty, the optimum of wellness and longevity, and employs extensive therapies and treatment in the preventive health care field far beyond just cholesterol testing and mammogram, by American Academy of Anti-aging Medicine. Aging theories is dived into two main theories, genetic control theory and acquired theory. Though many aging theories have been developed, any single theory is not universally accepted. Aging is defined as a time-related decline in physiological functions and changes in morphology. Aging is usually evaluated by questionnaires (AGHDA), self-test, aging biomarkers tests, and biological age measurements. Biological age measurement is usually considered as the index to evaluate the overall health status and aging degree in clinical practice. The goal of aging management is not only to treat age-related diseases, but to improve the diverse function of body and improve quality of life. Five major methods for aging management are the elimination of risk factors, management of chronic diseases, caloric restriction with nutritional balance, medium-intensity regular exercise, and stress management. Many other methods, such as, anti-oxidant therapy, hormone replacement, smart drugs, immune boosters, detoxification, and alternative medicine have been tried for aging management.

Hallmarks and Biomarkers of Skin Senescence: An Updated Review of Skin Senotherapeutics

Aging is a complex process characterized by an ongoing decline in physiological functions, leading to degenerative diseases and an increased probability of death. Cellular senescence has been typically considered as an anti-proliferative process; however, the chronic accumulation of senescent cells contributes to tissue dysfunction and aging. In this review, we discuss some of the most important hallmarks and biomarkers of cellular senescence with a special focus on skin biomarkers, reactive oxygen species (ROS), and senotherapeutic strategies to eliminate or prevent senescence. Although most of them are not exclusive to senescence, the expression of the senescence-associated beta-galactosidase (SA-β-gal) enzyme seems to be the most reliable biomarker for distinguishing senescent cells from those arrested in the cell cycle. The presence of a stable DNA damage response (DDR) and the accumulation of senescence-associated secretory phenotype (SASP) mediators and ROS are the most representative hallmarks for senescence. Senotherapeutics based on natural compounds such as quercetin, naringenin, and apigenin have shown promising results regarding SASP reduction. These compounds seem to prevent the accumulation of senescent cells, most likely through the inhibition of pro-survival signaling pathways. Although studies are still required to verify their short- and long-term effects, these therapies may be an effective strategy for skin aging.

A novel peptide derived from Haematococcus pluvialis residue exhibits anti-aging activity in Caenorhabditis elegans via the insulin/IGF-1 signaling pathway.

To explore the value of Haematococcus pluvialis (H. pluvialis) residue remaining after astaxanthin extraction and being discarded uneconomically, in our previous study, we discovered a novel peptide (HPp) as a potential bioactive component. However, the possible anti-aging activity in vivo was not illuminated. In this study, the capacity of extending the lifespan and the mechanism based on Caenorhabditis elegans (C. elegans) were determined. The results showed that 100 μM HPp not only enhanced the lifespan of C. elegans in normal environments by 20.96% but also strengthened the lifespan in oxidative and thermal conditions effectively. Moreover, HPp succeeded in lessening the decline in physiological functions of aging worms. In terms of antioxidant efficacy, SOD and CAT enzyme activity were promoted, but the level of MDA was diminished significantly after HPp treatment. Subsequent analysis directly reflected the relationship between higher stress resistance and up-regulation of skn-1 and hsp-16.2, and between greater antioxidant ability and up-regulation of sod-3 and ctl-2. Further studies illustrated that HPp up-graded the mRNA transcription of the genes associated with the insulin/insulin-like growth factor signaling (IIS) pathway and some co-factors, including daf-16, daf-2, ins-18, and sir-2.1. Particularly, the activation of the IIS pathway required the regulation of subcellular localization of DAF-16/FOXO. Taken together, HPp could promote longevity with improved stress resistance and antioxidant properties in vivo through the IIS pathway. These data suggested that HPp might serve as a good source of anti-aging actives, and in particular, laid a foundation for the high value-added application of marine microalgae.

Drought stress effects on morphophysiological and quality characteristics of commercial carrot cultivars

The effects of drought stress on plant growth and development are getting more pronounced due to increasing influence of climate change on environmental stresses. Current study was devised to explore the drought effects on eight commercial carrot cultivars, having different root colors as a base for further studies to understand the response of carrot. Drought stress for 10 days was applied to carrot plants at taproot formation stage in semicontrolled greenhouse. The results revealed that orange and yellow colored carrot cultivars exhibited the least decline in physiological functioning (relative water contents and dry matter) that assisted in maintaining higher yield and quality attributes in contrast to purple and black carrot cultivars. However, anthocyanin contents in nonpurple cultivars Tendersweet and Solar Yellow showed 72% decrease, whereas in purple carrot cultivars 3-fold increase was observed in Eregli Black and Cosmic Purple. Beta-carotene contents showed 59% decrease in cultivar Eregli Black under drought; however, it was increased in cultivars Solar Yellow and Coral Orange by 17% and 3%, respectively. Sugar accumulation exhibited variable response of carrot cultivars; minimal sucrose contents in cultivars Cosmic Purple, Solar Yellow and Tendersweet were detected after they were subjected to drought. Overall, the results showed that cultivars Atomic Red and Coral Orange performed well under water scarce condition. We believe this study may help the researchers to move forward in understanding the drought effects for the selection of promising cultivars to be used in development of tolerant varieties with breeding strategies.

Epigenetic Signatures of Aging: A Comprehensive Study of Biomarker Discovery

Background: Aging is a complex biological process that is associated with a decline in physiological functions and an increased risk of age-related diseases. Despite advances in molecular biology and genetics, the underlying mechanisms of aging remain largely unknown. Study: The identification of biomarkers of aging would provide a powerful tool for monitoring the effects of aging and for developing interventions to improve healthspan. Aging is associated with alterations in genetics, epigenetic marks, telomere shortening, cell senescence, and changes in the expression of genes involved in metabolism, inflammation, and DNA damage repair. Epigenetic changes, including modifications to DNA methylation and histone acetylation patterns, play a critical role in the aging process. As we age, these changes can lead to altered gene expression and contribute to the development of age-related diseases such as cancer, Alzheimer’s disease (AD) and cardiovascular disease (CVD). Conclusion: The discovery of aging biomarkers that are sensitive to these epigenetic changes has the potential to revolutionize our understanding of the aging process and inform the development of interventions to improve healthspan and extend lifespan.

Spatial-temporal analysis of urban-rural differences in the development of elderly care institutions in China.

Aging is both a sign of rising life expectancy per capita and social progress, and a challenge for society. Due to the decline in physiological functions, the rate of illness has increased significantly, leading to a rise in demand for healthcare, life care and other elderly care. With the overlapping impact of an aging population, advanced aging, empty nesting families and the weakening of traditional elderly care functions, the issue of elderly care for the empty nesters, the elderly alone and the disabled has become more prominent and has become a focal point of concern for all sectors of society. As an important supplement to the elderly care service system, institutional care, together with home care, community care and rural care, are mutually complementary. The study establishes a panel database of urban and rural elderly-care institutions in 276 cities from 2010 to 2016, and uses comprehensive measurements to reveal the spatial-temporal changes of urban and rural elderly care institutions in China. First, in terms of spatial pattern, the overall score of elderly care institutions in urban areas shows a "double-high" spatial pattern of higher scores in coastal areas than inland areas, and higher scores in urban areas than in rural areas. In terms of the differences in the scores of secondary indicators, the eastern urban areas have higher scores than the rural areas for the indicators of facilities construction and nursing staff of elderly institutions, while the eastern rural areas have higher scores than their urban counterparts for the indicators of service recipients of elderly institutions. Second, in terms of temporal change, there is a clear "urban progress and rural regression" in the evolution of China's elderly care institutions. Third, in terms of spatial and temporal evolution, there is a clear spatial autocorrelation in the composite scores of urban and rural elderly care institutions in China, and the spatial autocorrelation of the composite scores of elderly care institutions shows a clustering pattern. The contradiction between the limited ability to pay of the elderly people staying in elderly care institutions and the huge demand for elderly care services is bound to affect the sustainability of the development of public elderly care institutions in both urban and rural areas. Due to historical factors, the marketisation of elderly care institutions in China started late and the marketisation of elderly care is not high. As the population ages, China's elderly-care institutions have begun to transform from public institutions of a welfare nature to those with some market mechanisms, but the overall transformation has been slow, resulting in the service guarantee system of elderly-care institutions lagging far behind the actual needs of the elderly. The long-term development of elderly care institutions must introduce market mechanisms, enhance the endogenous dynamics of elderly care institutions, correctly handle the relationship between fairness and efficiency of elderly care services, and improve the professionalism, income and treatment of elderly care staff while compensating for the lack of development of elderly care institutions and the inadequate layout of space, so as to continuously improve the service quality of elderly care institutions.

Antiretroviral protease inhibitors induce features of cellular senescence that are reversible upon drug removal.

Antiretroviral drugs have dramatically improved the prognosis of HIV-infected patients, with strikingly reduced morbidity and mortality. However, long-term use can be associated with signs of premature aging. Highly active antiretroviral therapy generally comprises two nucleoside reverse transcriptase inhibitors (NRTIs), with one of three additional antiretroviral drug classes, including protease inhibitors (PIs). One commonality between mitochondrial dysfunction (induced by NRTIs) and defects in lamin A (induced by PIs) is they can cause or accelerate cellular senescence, a state of essentially irreversible growth arrest, and the secretion of many bioactive molecules collectively known as the senescence-associated secretory phenotype (SASP). We hypothesized that senescent cells increase following treatment with certain HIV therapies. We compared the effects of two distinct HIV PIs: ritonavir-boosted atazanavir (ATV/r) and ritonavir-boosted darunavir (DRN/r), used in combination treatments for HIV infection. Upon ATV/r, but not DRN/r, treatment, cells arrested growth, displayed multiple features of senescence, and expressed significantly upregulated levels of many SASP factors. Furthermore, mice receiving sustained ATV/r treatment showed an increase in senescent cells and age-related decline in physiological function. However, removing treatment reversed the features of senescence observed in vivo and cell culture. Given how these features disappeared with drug removal, certain features of senescence may not be prognostic as defined by an irreversible growth arrest. Importantly, for patients that are treated or have been treated with ATV/r, our data suggest that switching to another PI that does not promote premature aging conditions (DRN/r) may improve the associated age-related complications.

REDUCED LEVELS OF NAD IN SKELETAL MUSCLE IN PEOPLE AGING WITH HIV INFECTION ON TREATMENT

Abstract People living with HIV (PLWH) are disproportionately burdened with multimorbidity and decline in physiologic function compared to their uninfected counterparts, but biological mechanisms that differentially contribute to the decline in muscle function in PLWH compared to uninfected people remains understudied. The study site was Brigham and Women’s Hospital, Harvard Medical School, Boston MA. We evaluated skeletal muscle tissue for levels of total NAD, NAD+ and NADH in middle-aged asymptomatic PLWH, coinfected with hepatitis C virus (HCV) and/or cytomegalovirus (CMV) and compared them to uninfected control participants. Of the 54 persons with muscle biopsy data, the mean age 57 years with 33% women. Total NAD levels declined in skeletal muscle in association with HIV infection, and was exacerbated by HCV and CMV coinfection, with lowest levels of total NAD, NAD+ and NADH among persons that were coinfected with all three viruses (P=0.015, P=0.014, P=0.076; respectively). Levels of total NAD, NAD+ and NADH in skeletal muscle were inversely associated with inflammation (P=0.014, P=0.013, P=0.055; respectively). Coinfections were also associated with measures of inflammation (CD4/CD8 ratio: P< 0.001 and sCD163: P< 0.001), immune activation (CD38 and HLA-DR expression on CD8 T cells: P< 0.001). Additionally, coinfection was associated with increased physiologic frailty, based on the VACS Index 1.0 assessment (P=0.001). Further research is warranted to determine the clinical relevance of preclinical deficits in NAD metabolites in skeletal muscle in association with viral coinfection and inflammation, as well as the observed association between viral coinfection and physiologic frailty.

The Role of Defence Mechanisms in Coping with Stress in PTSD Patients

In the context of the war in Ukraine, the risk of post-traumatic stress disorders increases, which in critical cases cause the development of chronic mental illnesses and a decline in physiological functions. In connection with the emergence of a feeling of helplessness due to the inability to act effectively in a dangerous situation, various psychological defence mechanisms are formed to overcome intrapsychic conflicts. The purpose of this stud was to investigate the dominant mechanisms in individuals with post-traumatic stress disorder who had been in regions with different scenarios for the development of hostilities since the beginning of the war, using the PlutchikKellerman-Conte methodology. The information was collected from people of different age categories, types of employment, educational qualification levels, and gender who were in Kyiv, Kharkiv, and Lviv during the first two months of the full-scale war and periodically moved through the territory of Central and Western Ukraine. Cases of short-term residence abroad were also considered during the study. The results of the tension of psychological defence indicate that in individuals with post-traumatic stress disorder that stayed in different regions of Central and Western Ukraine since the beginning of the war, the projection mechanism dominated (75%), and the substitution mechanisms (12.5%) and denial mechanisms (12.5%) were equally distributed. The dominance of the projection may indicate the transfer of intrapsychic conflict to the outside. In this case, the external world is perceived by the individual as the main carrier of the threat from which they need to protect themselves. Instead, denial may indicate ignoring certain aspects of reality. Respondents who are prone to substitution use the approach of transferring repressed emotions, which can be expressed in the form of anger, fear, and hostility towards more accessible objects that are no less dangerous than those that led to frustrating experiences. It was determined that the total sample tension does not exceed 50%. This may indicate the ability of patients with post-traumatic stress disorder to resolve intrapsychic conflicts that have developed at the moment. The results of the study may be of practical interest to specialists investigating the identification and generation of methods for the prevention and treatment of post-traumatic stress disorder

Associations between multiple metals exposure and biological aging: Evidence from the Dongfeng-Tongji cohort

Aging is related to a progressive decline in physiological functions and is affected by environmental factors. Metal exposures are linked with many health effects, but have poorly understood associations with aging. In this study, a total of 33,916 participants from the Dongfeng-Tongji cohort were included to establish biological age (BA) predictors by using recent advanced algorithms, Klemera and Doubal method (KDM) and Mahalanobis distance. Two biological aging indexes (BAIs), recorded as KDM-accel [the residual from regressing KDM-BA on chronological age] and physiological dysregulation (PD), were separately defined and tested on their associations with mortality by using Cox proportional hazard models. Among 3320 subjects with laboratory determinations of 23 metals in plasma, the individual and overall associations between these metals and BAIs were evaluated by using multiple-linear regression and weighted quantile sum (WQS) models. Both BAIs were prospectively associated with all-cause mortality among the whole participants [KDM-accel: HR(95%CI) = 1.23(1.18, 1.29); PD: HR(95%CI) = 1.37(1.31, 1.42)]. Each 1-unit increment in ln-transformed strontium and molybdenum were cross-sectionally associated with a separate 0.71- and 0.34-year increase in KDM-accel, and each 1 % increment in copper, rubidium, strontium, cobalt was cross-sectionally associated with a separate 0.10 %, 0.10 %, 0.09 %, 0.02 % increase in PD (all FDR < 0.05). The WQS models observed mixture effects of multi-metals on aging, with a 0.20-year increase in KDM-accel and a 0.04 % increase in PD for each quartile increase in ln-transformed concentrations of all metals [KDM-accel: β(95%CI) = 0.20(0.08, 0.32); PD: β(95%CI) = 0.04(0.02, 0.06)]. Our findings revealed that plasma strontium, molybdenum, copper, rubidium and cobalt were associated with accelerated aging. Multi-metals exposure showed mixture effects on the aging process, which highlights potential preventative interventions.

A study protocol for a randomized controlled trial to assess the efficacy of Baduanjin exercise on older adults with sarcopenia in China

BackgroundAccompanied by the decline of physiological functions, the decrease of physical activity, and comorbidities, older adults are susceptible to sarcopenia because of accelerated loss of muscle mass. Resistance training is recommended by different clinical practice guidelines. However, most older adults have difficulty in taking recommended high-load resistance training programs, and there are limited exercise options form them. Baduanjin, a traditional Chinese mind-body exercise with relatively low intensity and simple movements, has the potential benefits of improving physical functions and may be feasible in treating sarcopenia and preventing its adverse health outcomes in older patients. With the emergence of the concept of gut-muscle axis, this study aims to determine the efficacy of Baduanjin exercise on Chinese older adults with sarcopenia and explore its underlying mechanism.MethodsThis is a 24-week, assessor-blinded, randomized controlled trial. Individuals aged 60 to 84 years old will be screened for sarcopenia. 90 participants with sarcopenia will be enrolled and randomly assigned (1:1) into the Baduanjin exercise or resistance training group, and 20 participants without sarcopenia will be set as the non-sarcopenia control group. The primary outcome is the scores of Short Physical Performance Battery. The secondary outcomes are body composition, handgrip strength, walking speed, global cognitive function, and incidence of falls. These outcomes will be assessed at baseline, the 12th week and the 24th week. While stool samples from participants will be collected at baseline and the 24th week for analyzing the abundance of gut microbiome. Data will be analyzed in an intention-to-treat protocol.DiscussionThe results of this study will determine whether Baduanjin exercise can be an alternative non-pharmacological approach for older adults with sarcopenia. If they can show positive significance, it will promote Baduanjin exercise in clinical practice among these patients and inform further research involving exercise interventions on the optimal types, timing, and intensity to ameliorate sarcopenia for elderly people.Trial registrationChinese Clinical Trial Registry; Registration number: ChiCTR2100051871; Prospectively registered on October 8th, 2021.

A Glb1-2A-mCherry reporter monitors systemic aging and predicts lifespan in middle-aged mice

The progressive decline of physiological function and the increased risk of age-related diseases challenge healthy aging. Multiple anti-aging manipulations, such as senolytics, have proven beneficial for health; however, the biomarkers that label in vivo senescence at systemic levels are lacking, thus hindering anti-aging applications. In this study, we generate a Glb1+/m‒Glb1-2A-mCherry (GAC) reporter allele at the Glb1 gene locus, which encodes lysosomal β-galactosidase—an enzyme elevated in tissues of old mice. A linear correlation between GAC signal and chronological age is established in a cohort of middle-aged (9 to 13 months) Glb1+/m mice. The high GAC signal is closely associated with cardiac hypertrophy and a shortened lifespan. Moreover, the GAC signal is exponentially increased in pathological senescence induced by bleomycin in the lung. Senolytic dasatinib and quercetin (D + Q) reduce GAC signal in bleomycin treated mice. Thus, the Glb1-2A-mCherry reporter mice monitors systemic aging and function decline, predicts lifespan, and may facilitate the understanding of aging mechanisms and help in the development of anti-aging interventions.

Defining FiTNEss for treatment for multiple myeloma

Improving the healthspan—the length of the lifespan spent free of disease—and prolonging the human lifespan in general are important objectives both in medicine and for society. The difference between lifespan and healthspan encompasses not only the influence of disease, but also of rapid physiological deterioration and its consequent risk of concomitant illness and polypharmacy, further augmenting physiological decompensation—frailty. Frailty is a functional term that refers to a decline in physiological function, leading to dependency, vulnerability to stressors, and a high risk of poor health-related outcomes (eg, metabolic disorders, infections, and cancer), which results in an increased risk of morbidity and mortality.

A computational roadmap to electronic drugs.

A growing number of complex neurostimulation strategies promise symptom relief and functional recovery for several neurological, psychiatric, and even multi-organ disorders. Although pharmacological interventions are currently the mainstay of treatment, neurostimulation offers a potentially effective and safe alternative, capable of providing rapid adjustment to short-term variation and long-term decline of physiological functions. However, rapid advances made by clinical studies have often preceded the fundamental understanding of mechanisms underlying the interactions between stimulation and the nervous system. In turn, therapy design and verification are largely driven by clinical-empirical evidence. Even with titanic efforts and budgets, it is infeasible to comprehensively explore the multi-dimensional optimization space of neurostimulation through empirical research alone, especially since anatomical structures and thus outcomes vary dramatically between patients. Instead, we believe that the future of neurostimulation strongly depends on personalizable computational tools, i.e. Digital Neuro Twins (DNTs) to efficiently identify effective and safe stimulation parameters. DNTs have the potential to accelerate scientific discovery and hypothesis-driven engineering, and aid as a critical regulatory and clinical decision support tool. We outline here how DNTs will pave the way toward effective, cost-, time-, and risk-limited electronic drugs with a broad application bandwidth.

The effect of growth hormone-induced cellular behavior and signaling properties on induced cellular senescence in human mesenchymal stem cells

Senescence is associated with a decline in physiological function, which is accompanied by onset of diseases. Growth hormone (GH) is a class of growth-promoting cytokines with reduced secretion in aging populations. However, the effect of senescence on GH bioactivity is not fully understood in human mesenchymal stem cells (hMSCs). In this work, GH-induced cellular behavior and intracellular signaling transduction were explored in senescent hMSCs. Therefore, hMSCs were used to establish a senescence model by H2O2 treatment for this study. First, we investigated the effects of cellular senescence on the cell behavior of GH. The experimental results suggested that GH could not be internalized into the nucleus, and a significant reduction in GH internalization into the cytoplasm was observed in senescent hMSCs compared to the control group. Second, the effect of cellular senescence on GH-mediated intracellular signaling pathways was investigated by Western blotting. For this, the signaling molecule activation of Janus kinase 2 (JAK2)/signal transducer and activator transcription (STAT) stimulated by GH was detected. Our data indicated that the signaling intensity of p-JAK2, p-STAT5, p-STAT3 and p-STAT1 was considerably weakened. Taken together, these findings provide important insights into the impaired effects of cellular senescence on the biological activity of GH.