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Obstructive Sleep Apnea-hypopnea Syndrome as a Novel Potential Risk for Aging PDF (395KB)
Yayong Li, Yina Wang
IL-6 Levels Influence 3-Month All-Cause Mortality in Frail Hospitalized Older Patients PDF (371KB)
Stefano Rizza, Pasquale Morabito, Livia De Meo, Alessio Farcomeni, Giulia Testorio, Marina Cardellini, Marta Ballanti, Francesca Davato, Chiara Pecchioli, Giovanni Di Cola, Maria Mavilio, Massimo Federici
Outcomes in Endovascular Therapy for Basilar Artery Occlusion: Intracranial Atherosclerotic Disease vs. Embolism PDF (507KB)
Longfei Wu,Gary B. Rajah,Eric E. Cosky,Xiling Wu,Chuanhui Li,Jian Chen,Wenbo Zhao,Di Wu,Yuchuan Ding,Xunming Ji
Research progress on Mesenchymal Stem Cells (MSCs), Adipose-Derived Mesenchymal Stem Cells (AD-MSCs), Drugs, and Vaccines in Inhibiting COVID-19 Disease PDF (574KB)
Pietro Gentile, Aris Sterodimas, Jacopo Pizzicannella, Claudio Calabrese, Simone Garcovich
Terminal Schwann Cell Aging: Implications for Age-Associated Neuromuscular Dysfunction PDF (913KB)
Sandra Fuertes-Alvarez, Ander Izeta
  • Current Issue
      01 August 2020, Volume 11 Issue 4 Previous Issue   
    For Selected: View Abstracts Toggle Thumbnails
    Geroscience in the Age of COVID-19
    Barzilai Nir,Appleby James C,Austad Steven N,Cuervo Ana Maria,Kaeberlein Matt,Gonzalez-Billault Christian,Lederman Stephanie,Stambler Ilia,Sierra Felipe
    Aging and disease. 2020, 11 (4): 725-729.   DOI: 10.14336/AD.2020.0629
    Abstract   HTML   PDF (222KB) ( 164 )

    The data on COVID-19 is clear on at least one point: Older adults are most vulnerable to hospitalization, disability and death following infection with the novel coronavirus. Therefore, therapeutically addressing degenerative aging processes as the main risk factors appears promising for tackling the present crisis and is expected to be relevant when tackling future infections, epidemics and pandemics. Therefore, utilizing a geroscience approach, targeting aging processes to prevent multimorbidity, via initiating broad clinical trials of potential geroprotective therapies, is recommended.

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    Letter to the Editor
    Potential Using of Fat-derived Stromal Cells in the Treatment of Active Disease, and also, in Both Pre- and Post-Periods in COVID-19
    Copcu Hasim Eray
    Aging and disease. 2020, 11 (4): 730-736.   DOI: 10.14336/AD.2020.0621
    Abstract   HTML   PDF (271KB) ( 39 )

    The whole world is fighting with the COVID-19 pandemic, which traps people home, causing high business and economic losses, and above all, leads to very serious deaths. The lack of a valid, accepted treatment protocol and vaccine that leads to continued treatment searches. Leng et al published their article in the Aging and Disease journal, which demonstrates that mesenchymal stem cells (MSCs) can be used for COVID-19 treatment. Adipose tissue is one of the most important MSCs sources in the body, and adipose derived stromal cells (ADSCs) from adipose tissue are also one of the most valuable components of stromal vascular fraction (SVF). Finally, Gentile and Sterodimas, have also published their article for the potential use of SVF in COVID-19 treatment in Aging and Disease journal. Their publication has been a guide in many ways. Adipose tissue-derived stromal cells have three main features: Immunomodulatory, anti-inflammatory and regenerative. Immunomodulator effects are used as a preventive in patients prone to disease; its anti-inflammatory effects may allow them to be used as a therapeutic during active disease period and finally regenerative effects to repair post-disease sequale. Those cells can be obtained not only enzymatically, but also mechanically with very benefits. They can be delivered not only systemically through the IV route but also to the target organ with a carrier. While suggesting any adipose tissue-derived treatment method possibility, the relation of adipose tissue COVID-19 should not be ignored. Because, COVID-19 shows its effect through ACE-2 and adipose tissue is very rich and important tissue in terms of ACE-2.

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    COVID-19 and Senotherapeutics: Any Role for the Naturally-occurring Dipeptide Carnosine?
    Hipkiss Alan R
    Aging and disease. 2020, 11 (4): 737-741.   DOI: 10.14336/AD.2020.0518
    Abstract   HTML   PDF (257KB) ( 62 )

    It is suggested that the non-toxic dipeptide carnosine (beta-alanyl-L-histidine) should be examined as a potential protective agent against COVID-19 infection and inflammatory consequences especially in the elderly. Carnosine is an effective anti-inflammatory agent which can also inhibit CD26 and ACE2 activity. It is also suggested that nasal administration would direct the peptide directly to the lungs and escape the attention of serum carnosinase.

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    Decreased Naïve T-cell Production Leading to Cytokine Storm as Cause of Increased COVID-19 Severity with Comorbidities
    Schwartz Michael D,Emerson Stephen G,Punt Jennifer,Goff Willow D
    Aging and disease. 2020, 11 (4): 742-745.   DOI: 10.14336/AD.2020.0619
    Abstract   HTML   PDF (247KB) ( 130 )

    Aging, type 2 diabetes, and male gender are major risk factors leading to increased COVID-19 morbidity and mortality. Thymic production and the export of naïve T cells decrease with aging through the effects of androgens in males and in type 2 diabetes. Furthermore, with aging, recovery of naïve T-cell populations after bone marrow transplantation is delayed and associated with an increased risk of chronic graft vs. host disease. Severe COVID-19 and SARS infections are notable for severe T-cell depletion. In COVID-19, there is unique suppression of interferon signaling by infected respiratory tract cells with intact cytokine signaling. A decreased naïve T-cell response likely contributes to an excessive inflammatory response and increases the odds of a cytokine storm. Treatments that improve naïve T-cell production may prove to be vital COVID-19 therapies, especially for these high-risk groups.

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    Bioactive Lipids as Mediators of the Beneficial Action(s) of Mesenchymal Stem Cells in COVID-19
    Das Undurti N
    Aging and disease. 2020, 11 (4): 746-755.   DOI: 10.14336/AD.2020.0521
    Abstract   HTML   PDF (794KB) ( 92 )

    It is proposed that the beneficial action of mesenchymal stem cells (MSCs) in COVID-19 and other inflammatory diseases could be attributed to their ability to secrete bioactive lipids (BALs) such as prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) and other similar BALs. This implies that MSCs that have limited or low capacity to secrete BALs may be unable to bring about their beneficial actions. This proposal implies that pretreatment of MSCs with BALs enhance their physiological action or improve their (MSCs) anti-inflammatory and disease resolution capacity to a significant degree. Thus, the beneficial action of MSCs reported in the management of COVID-19 could be attributed to their ability to secrete BALs, especially PGE2 and LXA4. Since PGE2, LXA4 and their precursors AA (arachidonic acid), dihomo-gamma-linolenic acid (DGLA) and gamma-linolenic acid (GLA) inhibit the production of pro-inflammatory IL-6 and TNF-α, they could be employed to treat cytokine storm seen in COVID-19, immune check point inhibitory (ICI) therapy, sepsis and ARDS (acute respiratory disease). This is further supported by the observation that GLA, DGLA and AA inactivate enveloped viruses including COVID-19. Thus, infusions of appropriate amounts of GLA, DGLA, AA, PGE2 and LXA4 are of significant therapeutic benefit in COVID-19, ICI therapy and other inflammatory conditions including but not limited to sepsis. AA is the precursor of both PGE2 and LXA4 suggesting that AA is most suited for such preventive and therapeutic approach.

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    Age-induced NLRP3 Inflammasome Over-activation Increases Lethality of SARS-CoV-2 Pneumonia in Elderly Patients
    Lara Pedro C,Macías-Verde David,Burgos-Burgos Javier
    Aging and disease. 2020, 11 (4): 756-762.   DOI: 10.14336/AD.2020.0601
    Abstract   HTML   PDF (270KB) ( 48 )

    Age is one of the most important prognostic factors associated to lethality in SARS-CoV-2 infection. In multivariate analysis, advanced age was an independent risk factor for death. Recent studies suggest a role for the nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome activation in lung inflammation and fibrosis in SARS-CoV and SARS-CoV-2 infections. Increased NLRP3/ apoptosis-associated speck-like protein (ASC) mRNA expression and increased caspase-1 activity, have been observed in aged lung, provoking increased and heightened expression levels of mature Interleukin (IL)-1β and IL-18 in aged individuals. Aged individuals have a basal predisposition to over-react to infection, displaying an increased hyper-inflammatory cascade, that seems not to be fully physiologically controlled. NLRP3 inflammasome is over-activated in aged individuals, through deficient mitochondrial functioning, increased mitochondrial Reactive Oxigen Species (mtROS) and/or mitochondrial (mt)DNA, leading to a hyper-response of classically activated macrophages and subsequent increases in IL-1 β. This NLRP3 over-activated status in elderly individuals, is also observed in telomere dysfunctional mice models. In our opinion, the NLRP3 inflammasome plays a central role in the increased lethality observed in elderly patients infected by COVID-19. Strategies blocking inflammasome would deserve to be studied.

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    Short Communications
    Clinical features and risk factors for ICU admission in COVID-19 patients with cardiovascular diseases
    He Feng,Quan Yibo,Lei Ming,Liu Riguang,Qin Shuguang,Zeng Jun,Zhao Ziwen,Yu Na,Yang Liuping,Cao Jie
    Aging and disease. 2020, 11 (4): 763-769.   DOI: 10.14336/AD.2020.0622
    Abstract   HTML   PDF (531KB) ( 112 )

    Previous studies on coronavirus disease 2019 (COVID-19) have focused on the general population. However, cardiovascular disease (CVD) is a common comorbidity that has rarely been investigated in detail. This study aims to describe clinical characteristics and determine risk factors for intensive care unit (ICU) admission of COVID-19 patients with CVD. In this retrospective cohort study, we included 288 adult patients with COVID-19 in Guangzhou Eighth People's Hospital from January 15, 2020 to March 10, 2020. Demographic characteristics, laboratory results, radiographic findings, complications, and treatments were recorded and compared between CVD and non-CVD groups. A binary logistic regression model was used to identify risk factors associated with ICU admission for infected patients with underlying CVD. COVID-19 patients in the CVD group were older and had higher levels of troponin I (TnI), C-reactive protein (CRP), and creatinine. They were also more prone to develop into severe or critically severe cases, receive ICU admission, and require respiratory support treatment. Multivariate regression analysis showed that the following were risk factors for ICU admission in COVID-19 patients with CVD: each 1-year increase in age (odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02-1.17; p = 0.018); respiratory rate over 24 times per min (OR, 25.52; 95% CI, 5.48-118.87; p < 0.0001); CRP higher than 10 mg/L (OR, 8.12; 95% CI, 1.63-40.49; p = 0.011); and TnI higher than 0.03 μg/L (OR, 9.14; 95% CI, 2.66-31.43; p < 0.0001). Older age, CRP greater than 10 mg/L, TnI higher than 0.03 μg/L, and respiratory rate over 24 times per minute were associated with increasing odds of ICU admission in COVID-19 patients with CVD. Investigating and monitoring these factors could assist in the risk stratification of COVID-19 patients with CVD at an early stage.

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    Orginal Article
    Prevalence of High Jugular Bulb across Different Stages of Adulthood in A Chinese Population
    Wang Jingjing,Feng Yanmei,Wang Hui,Li Chunyan,Wu Yaqin,Shi Haibo,Yin Shankai,Chen Zhengnong
    Aging and disease. 2020, 11 (4): 770-776.   DOI: 10.14336/AD.2020.0215
    Abstract   HTML   PDF (456KB) ( 98 )

    Pulsatile tinnitus, ear fullness, vertigo, hearing disorders, and vestibular dysfunction have been found to be related to high jugular bulb. Anatomical variation in this region also affects surgical planning and approaches. Therefore, knowledge on the detailed anatomy of the high jugular bulb is critical for middle ear and lateral skull base surgery. Prevalence of high jugular bulb is uncertain as data are usually derived from temporal bone specimens and patient reports from hospitals. Therefore, a community-based epidemiological study is necessary to understand the significance of high jugular bulb anatomy. Here, we report a cross-sectional study to characterize the prevalence of high jugular bulb and jugular bulb size using a 3.0 T magnetic resonance imaging. Furthermore, we studied the relationship between the prevalence of high jugular bulb and age-related changes. We enrolled 4539 permanent residents (9078 ears) from two communities in the Shanghai region who underwent magnetic resonance imaging between 2007 and 2011. We divided participants into four subgroups according to age: 35-44 (early middle age), 45-54 (middle age), 55-64 (late middle age), and 65-75 (late adulthood) years. We found that the overall prevalence of high jugular bulb was 14.5% in a Chinese population. There was a higher prevalence of high jugular bulb on the right side and especially in women (both p < 0.001). The occurrence of high jugular bulb was higher in the early middle age group and gradually decreased with age, but was still present in the late adulthood group (p = 0.039). These findings provide useful information on the prevalence of high jugular bulb in a Chinese population and the distribution in age groups, suggesting that high jugular bulb should be considered, even in those without ear disorders. This work serves as a foundation for further research on the relationship between jugular bulb changes and disease symptoms.

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    β-Hydroxybutyrate Suppresses Lipid Accumulation in Aged Liver through GPR109A-mediated Signaling
    Lee A Kyoung,Kim Dae Hyun,Bang EunJin,Choi Yeon Ja,Chung Hae Young
    Aging and disease. 2020, 11 (4): 777-790.   DOI: 10.14336/AD.2019.0926
    Abstract   HTML   PDF (1076KB) ( 282 )

    Dietary interventions such as prolonged calorie restriction (CR) and intermittent fasting provide health benefits including a reduction in the inflammatory burden and regulation of energy metabolism. During CR, β-hydroxybutyrate (BHB) level is elevated in the serum. BHB is a ligand of GPR109A, which inhibits lipolysis and exerts anti-inflammatory effects on cells. During aging, comorbidities related to dyslipidemia are significantly associated with fatty liver. However, the underlying mechanisms of BHB in hepatic ER stress and dyslipidemia are unclear and remain to be elucidated. Here, we used aged rats that were administered with BHB and compared the modulatory effects of BHB through the GPR109A/AMPK pathway on the hepatic endoplasmic reticulum (ER) stress and lipid accumulation to CR rats. BHB caused suppression of hepatic ER stress and lipid accumulation through GPR109A/AMPK pathway in the aged rats. Aged rats of both treatment groups showed reduced cAMP level and PKA phosphorylation. Furthermore, AMPK-Ser173 phosphorylation via PKA was decreased, whereas AMPK-Thr172 phosphorylation was increased by BHB and CR. Further supporting evidence was provided in HepG2 cells that BHB inhibited ER stress and lipid accumulation induced by palmitate. These results suggest that BHB activates GPR109A and regulates the activation of AMPK. These findings were further confirmed by GPR109A-siRNA transfection in vitro. In addition, BHB treatment elevated the protein levels of AMPK leading to significant inhibition of hepatic steatosis, whereas AMPK-siRNA treatment abolished these effects. Taken together, these findings suggest that BHB could be a effective molecule that mimics CR in ameliorating age-related hepatic lipid accumulation via GPR109A signaling pathway.

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    Gait Characteristics and Brain Activity in Parkinson’s Disease with Concomitant Postural Abnormalities
    Yao Meng-sha,Zhou Li-che,Tan Yu-yan,Jiang Hong,Chen Zhi-chun,Zhu Lin,Luo Ning-di,Wu Quan-zhou,Kang Wen-yan,Liu Jun
    Aging and disease. 2020, 11 (4): 791-800.   DOI: 10.14336/AD.2019.0929
    Abstract   HTML   PDF (770KB) ( 217 )

    To explore the underlying pathogenic mechanism of Parkinson’s disease (PD) with concomitant postural abnormalities (PDPA) through the relationship between its gait and brain function characteristics. PD patients from the neurology outpatient clinic at Ruijin Hospital were recruited and grouped according to whether postural abnormalities (including camptocormia and Pisa syndrome) were present. PD-related scale assessments, three-dimensional gait tests and brain resting-state functional magnetic imaging were performed and analyzed. The gait characteristics independently associated with PDPA were decreased pelvic obliquity angle and progressive downward movement of the center of mass during walking. PDPA features included decreased functional connectivity between the left insula and bilateral supplementary motor area, which was significantly correlated with reduced Berg Balance Scale scores. Functional connectivity between the right insula and bilateral middle frontal gyrus was decreased and significantly correlated with a decreased pelvic obliquity angle and poor performance on the Timed Up and Go test. Moreover, through diffusion tensor imaging analysis, the average fractional anisotropy value of the fibers connecting the left insula and left supplementary motor area was shown to be decreased in PDPA. There is decreased functional connectivity among the insula, supplementary motor area and middle frontal gyrus with structural abnormalities between the left insula and the left supplementary motor area; these changes in brain connectivity are probably among the causes of gait dysfunction in PDPA and provide some clues regarding the pathogenic mechanisms of PDPA.

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    Artemisinin Improved Neuronal Functions in Alzheimer's Disease Animal Model 3xtg Mice and Neuronal Cells via Stimulating the ERK/CREB Signaling Pathway
    Zhao Xia,Li Shuai,Gaur Uma,Zheng Wenhua
    Aging and disease. 2020, 11 (4): 801-819.   DOI: 10.14336/AD.2019.0813
    Abstract   HTML   PDF (1664KB) ( 307 )

    The most common form of dementia is Alzheimer’s disease which is characterized by memory loss and cognitive disorders. The pathogenesis of Alzheimer’s disease is not known at present but toxicity of amyloid-beta is one of the central hypotheses. Amyloid-beta can stimulate the production of reactive oxygen species (ROS), cause oxidative stress, damage mitochondrial, cause inflammatory reactions and activate apoptosis related factors which lead to the neuronal death. In this study, we found that artemisinin, a first line antimalarial drug used in clinic for decades, improved the cognitive functions in Alzheimer’s disease animal model 3xTg mice. Further study showed that artemisinin reduced the deposition of amyloid-beta and tau protein, reduced the release of inflammation factors and apoptosis factors, and thereby reduced the neuronal cell death. Western blot assay showed that artemisinin stimulated the activation of ERK/CREB signaling pathway. Consistent with these results, artemisinin concentration-dependently promoted the survival of SH-SY5Y cell against toxicity of amyloid-beta protein 1-42 induced ROS accumulation, caspase activation and apoptosis. Artemisinin also stimulated the phosphorylation of ERK1/2 and CREB in SH-SY5Y cells in time and concentration-dependent manner. Inhibition of ERK/CREB pathway attenuated the protective effect of artemisinin. These data put together suggested that artemisinin has the potential to protect neuronal cells in vitro as well as in vivo animal model 3xTg mice via, at least in part, the activation of the ERK/CREB pathway. Our findings also strongly support the potential of artemisinin as a new multi-target drug that can be used for preventing and treating the Alzheimer’s disease.

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    Remote Ischemic Conditioning Improves Attention Network Function and Blood Oxygen Levels in Unacclimatized Adults Exposed to High Altitude
    Li Sijie,Han Cong,Asmaro Karam,Quan Shanyi,Li Ming,Ren Changhong,Zhang Jun,Zhao Wenbo,Xu Jiali,Liu Zhiwen,Zhang Peng,Zhu Lingling,Ding Yuchuan,Wang Kai,Ji Xunming,Duan Lian
    Aging and disease. 2020, 11 (4): 820-827.   DOI: 10.14336/AD.2019.0605
    Abstract   HTML   PDF (368KB) ( 243 )

    Remote ischemic conditioning (RIC) confers protection on major organs from hypoxic/ischemic injuries; however, its impacts on attention network function and blood oxygen levels in unacclimatized adults exposed to high altitudes have yet to be elucidated. In this study, we recruited 120 healthy male volunteers, of which one was exposed to high altitude and the other was exposed to low altitude. The two cohorts were further divided into RIC and sham control groups. The attentional network test (ANT) was performed to evaluate cognitive function before and after RIC treatment. Other outcomes such as heart rate, blood pressure, blood oxygen saturation, cerebral tissue oxygenation index (CTOI), and cerebrovascular hemodynamic indices were also evaluated. Prior to RIC treatment, there were no significant differences in orienting or executive function between the treatment and control arms of either cohort. Alerting function was significantly lower in the high-altitude cohort than in the low-altitude cohort. There were significant reductions in both blood oxygen and CTOI in the high-altitude cohort relative to the low-altitude cohort, while the pulse index (PI) of the former cohort was significantly increased. After RIC treatment, there was a significant difference in alerting function between the high-altitude RIC group and its associated control. The CTOI of the treatment group increased from 60.39±3.40% to 62.78±4.40%, and blood oxygenation also improved. Furthermore, this group showed a significant reduction in its PI. Exposure to high-altitude environments had a significant impact on alerting function, blood oxygen, CTOI, and PI. RIC ameliorated changes in attentional function, as well as blood oxygen and CTOI, suggesting that it potentially alters cerebrovascular compliance upon exposure to high altitude.

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    TGF-β Signaling: A Therapeutic Target to Reinstate Regenerative Plasticity in Vascular Dementia?
    Kandasamy Mahesh,Anusuyadevi Muthuswamy,Aigner Kiera M,Unger Michael S,Kniewallner Kathrin M,Sousa Diana M Bessa de,Altendorfer Barbara,Mrowetz Heike,Bogdahn Ulrich,Aigner Ludwig
    Aging and disease. 2020, 11 (4): 828-850.   DOI: 10.14336/AD.2020.0222
    Abstract   HTML   PDF (1219KB) ( 85 )

    Vascular dementia (VaD) is the second leading form of memory loss after Alzheimer's disease (AD). Currently, there is no cure available. The etiology, pathophysiology and clinical manifestations of VaD are extremely heterogeneous, but the impaired cerebral blood flow (CBF) represents a common denominator of VaD. The latter might be the result of atherosclerosis, amyloid angiopathy, microbleeding and micro-strokes, together causing blood-brain barrier (BBB) dysfunction and vessel leakage, collectively originating from the consequence of hypertension, one of the main risk factors for VaD. At the histopathological level, VaD displays abnormal vascular remodeling, endothelial cell death, string vessel formation, pericyte responses, fibrosis, astrogliosis, sclerosis, microglia activation, neuroinflammation, demyelination, white matter lesions, deprivation of synapses and neuronal loss. The transforming growth factor (TGF) β has been identified as one of the key molecular factors involved in the aforementioned various pathological aspects. Thus, targeting TGF-β signaling in the brain might be a promising therapeutic strategy to mitigate vascular pathology and improve cognitive functions in patients with VaD. This review revisits the recent understanding of the role of TGF-β in VaD and associated pathological hallmarks. It further explores the potential to modulate certain aspects of VaD pathology by targeting TGF-β signaling.

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    DICER1 in the Pathogenesis of Age-related Macular Degeneration (AMD) - Alu RNA Accumulation versus miRNA Dysregulation
    Kaarniranta Kai,Pawlowska Elzbieta,Szczepanska Joanna,Blasiak Janusz
    Aging and disease. 2020, 11 (4): 851-862.   DOI: 10.14336/AD.2019.0809
    Abstract   HTML   PDF (723KB) ( 284 )

    DICER1 deficiency in the retinal pigment epithelium (RPE) was associated with the accumulation of Alu transcripts and implicated in geographic atrophy (GA), a form of age-related macular degeneration (AMD), an eye disease leading to blindness in millions of people. Although the exact mechanism of this association is not fully known, the activation of the NLRP3 inflammasome, maturation of caspase-1 and disruption in mitochondrial homeostasis in RPE cells were shown as critical for it. DICER1 deficiency results in dysregulation of miRNAs and changes in the expression of many genes important for RPE homeostasis, which may also contribute to AMD. DICER1 deficiency can change the functions of the miR-183/96/182 cluster that regulates photoreceptors and their synaptic transmission. Aging, the main AMD risk factor, is associated with decreased expression of DICER1 and changes in its diurnal pattern that are not synchronized with circadian regulation in the retina. The initial insult inducing DICER1 deficiency in AMD may be oxidative stress, another major risk factor of AMD, but further studies on the role of deficient DICER1 in AMD pathogenesis and its therapeutic potential are needed.

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    Exercise Programs for Muscle Mass, Muscle Strength and Physical Performance in Older Adults with Sarcopenia: A Systematic Review and Meta-Analysis
    Bao Wangxiao,Sun Yun,Zhang Tianfang,Zou Liliang,Wu Xiaohong,Wang Daming,Chen Zuobing
    Aging and disease. 2020, 11 (4): 863-873.   DOI: 10.14336/AD.2019.1012
    Abstract   HTML   PDF (1300KB) ( 325 )

    Sarcopenia is an age-related condition that is characterized by progressive and generalized loss of muscle mass and function. Exercise treatment has been the most commonly used intervention among elderly populations. We performed a systematic review and meta-analysis to evaluate the available literature related to the effects of exercise interventions/programs on muscle mass, muscle strength and physical performance in older adults with sarcopenia. We searched PubMed, EMBASE, MEDLINE and the Web of Science for randomized controlled trials and controlled clinical trials exploring exercise in older adults with sarcopenia published through July 2019 without any language restrictions. Pooled analyses were conducted using Review Manager 5.3, with standardized mean differences (SMDs) and fixed-effect models. A total of 3898 titles and abstracts were initially identified, and 22 studies (1041 individuals, 80.75% females, mean age ranged from 60.51 to 85.90 years) were included in the meta-analysis. The exercise programs in the studies consisted of 30 to 80 min of training, with 1 to 5 training sessions weekly for 6 to 36 weeks. Muscle strength (grip strength [SMD 0.57, 95 % CI 0.42 to 0.73, P <0.00001] and timed five chair stands [SMD -0.56, 95 % CI -0.85 to -0.28, P < 0.0001]) and physical performance (gait speed [SMD 0.44, 95 % CI 0.26 to 0.61, P < 0.00001] and the timed up and go test [SMD -0.97, 95 % CI -1.22 to -0.72, P < 0.00001]) showed significant improvement following exercise treatment, while no differences in muscle mass (ASM [SMD 0.15, 95 % CI -0.05 to 0.36, P = 0.15] and ASM/height2 [SMD 0.21, 95 % CI -0.05 to 0.48, P = 0.12]) were detected. Exercise programs showed overall significant positive effects on muscle strength and physical performance but not on muscle mass in sarcopenic older adults.

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    Multi-organ Dysfunction in Patients with COVID-19: A Systematic Review and Meta-analysis
    Wu Ting,Zuo Zhihong,Kang Shuntong,Jiang Liping,Luo Xuan,Xia Zanxian,Liu Jing,Xiao Xiaojuan,Ye Mao,Deng Meichun
    Aging and disease. 2020, 11 (4): 874-894.   DOI: 10.14336/AD.2020.0520
    Abstract   HTML   PDF (3152KB) ( 108 )

    This study aimed to provide systematic evidence for the association between multiorgan dysfunction and COVID-19 development. Several online databases were searched for articles published until May 13, 2020. Two investigators independently selected trials, extracted data, and evaluated the quality of individual trials. Single-arm meta-analysis was performed to summarize the clinical features of confirmed COVID-19 patients. Fixed effects meta-analysis was performed for clinically relevant parameters that were closely related to the patients’ various organ functions. A total of 73 studies, including 171,108 patients, were included in this analysis. The overall incidence of severe COVID-19 and mortality were 24% (95% confidence interval [CI], 20%-28%) and 2% (95% CI, 1%-3%), respectively. Patients with hypertension (odds ratio [OR] = 2.40; 95% CI, 2.08-2.78), cardiovascular disease (CVD) (OR = 3.54; 95% CI, 2.68-4.68), chronic obstructive pulmonary disease (COPD) (OR=3.70; 95% CI, 2.93-4.68), chronic liver disease (CLD) (OR=1.48; 95% CI, 1.09-2.01), chronic kidney disease (CKD) (OR = 1.84; 95% CI, 1.47-2.30), chronic cerebrovascular diseases (OR = 2.53; 95% CI, 1.84-3.49) and chronic gastrointestinal (GI) disease (OR = 2.13; 95% CI, 1.12-4.05) were more likely to develop severe COVID-19. Increased levels of lactate dehydrogenase (LDH), creatine kinase (CK), high-sensitivity cardiac troponin I (hs-cTnI), myoglobin, creatinine, urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin were highly associated with severe COVID-19. The incidence of acute organ injuries, including acute cardiac injury (ACI); (OR = 11.87; 95% CI, 7.64-18.46), acute kidney injury (AKI); (OR=10.25; 95% CI, 7.60-13.84), acute respiratory distress syndrome (ARDS); (OR=27.66; 95% CI, 18.58-41.18), and acute cerebrovascular diseases (OR=9.22; 95% CI, 1.61-52.72) was more common in patients with severe COVID-19 than in patients with non-severe COVID-19. Patients with a history of organ dysfunction are more susceptible to severe conditions. COVID-19 can aggravate an acute multiorgan injury.

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    The Impact of CRISPR-Cas9 on Age-related Disorders: From Pathology to Therapy
    Caobi Allen,Dutta Rajib Kumar,Garbinski Luis D,Esteban-Lopez Maria,Ceyhan Yasemin,Andre Mickensone,Manevski Marko,Ojha Chet Raj,Lapierre Jessica,Tiwari Sneham,Parira Tiyash,El-Hage Nazira
    Aging and disease. 2020, 11 (4): 895-915.   DOI: 10.14336/AD.2019.0927
    Abstract   HTML   PDF (718KB) ( 318 )

    With advances in medical technology, the number of people over the age of 60 is on the rise, and thus, increasing the prevalence of age-related pathologies within the aging population. Neurodegenerative disorders, cancers, metabolic and inflammatory diseases are some of the most prevalent age-related pathologies affecting the growing population. It is imperative that a new treatment to combat these pathologies be developed. Although, still in its infancy, the CRISPR-Cas9 system has become a potent gene-editing tool capable of correcting gene-mediated age-related pathology, and therefore ameliorating or eliminating disease symptoms. Deleting target genes using the CRISPR-Cas9 system or correcting for gene mutations may ameliorate many different neurodegenerative disorders detected in the aging population. Cancer cells targeted by the CRISPR-Cas9 system may result in an increased sensitivity to chemotherapeutics, lower proliferation, and higher cancer cell death. Finally, reducing gene targeting inflammatory molecules production through microRNA knockout holds promise as a therapeutic strategy for both arthritis and inflammation. Here we present a review based on how the expanding world of genome editing can be applied to disorders and diseases affecting the aging population.

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    p300 in Cardiac Development and Accelerated Cardiac Aging
    Ghosh Asish K
    Aging and disease. 2020, 11 (4): 916-926.   DOI: 10.14336/AD.2020.0401
    Abstract   HTML   PDF (536KB) ( 144 )

    The heart is the first functional organ that develops during embryonic development. While a heartbeat indicates life, cessation of a heartbeat signals the end of life. Heart disease, due either to congenital defects or to acquired dysfunctions in adulthood, remains the leading cause of death worldwide. Epigenetics plays a key role in both embryonic heart development and heart disease in adults. Stress-induced vascular injury activates pathways involved in pathogenesis of accelerated cardiac aging that includes cellular dysfunction, pathological cardiac hypertrophy, diabetic cardiomyopathy, cardiac matrix remodeling, cardiac dysfunction and heart failure. Acetyltransferase p300 (p300), a major epigenetic regulator, plays a pivotal role in heart development during embryogenesis, as deficiency or abnormal expression of p300 leads to embryonic death at early gestation periods due to deformation of the heart and neural tube. Acetyltransferase p300 controls heart development through histone acetylation-mediated chromatin remodeling and transcriptional regulation of genes required for cardiac development. In adult hearts, p300 is differentially expressed in different chambers and epigenetically controls cardiac gene expression. Deregulation of p300, in response to prohypertrophic and profibrogenic stress signals, is associated with increased recruitment of p300 to several genes including transcription factors, increased acetylation of specific lysines in histones and transcription factors, altered chromatin organization, and increased hypertrophic and fibrogenic gene expression. Cardiac hypertrophy and myocardial fibrogenesis are common pathological manifestations of several stress-induced accelerated cardiac aging-related pathologies, including high blood pressure-induced or environmentally induced cardiac hypertrophy, myocardial infarction, diabetes-induced cardiomyopathy, and heart failure. Numerous studies using cellular and animal models clearly indicate that pharmacologic or genetic normalization of p300 activity has the potential to prevent or halt the progression of cardiac aging pathologies. Based on these preclinical studies, development of safe, non-toxic, small molecule inhibitors/epidrugs targeting p300 is an ideal approach to control accelerated cardiac aging-related deaths worldwide.

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    Sirtuins and their Biological Relevance in Aging and Age-Related Diseases
    Zhao Lijun,Cao Jianzhong,Hu Kexin,He Xiaodong,Yun Dou,Tong Tanjun,Han Limin
    Aging and disease. 2020, 11 (4): 927-945.   DOI: 10.14336/AD.2019.0820
    Abstract   HTML   PDF (655KB) ( 399 )

    Sirtuins, initially described as histone deacetylases and gene silencers in yeast, are now known to have many more functions and to be much more abundant in living organisms. The increasing evidence of sirtuins in the field of ageing and age-related diseases indicates that they may provide novel targets for treating diseases associated with aging and perhaps extend human lifespan. Here, we summarize some of the recent discoveries in sirtuin biology that clearly implicate the functions of sirtuins in the regulation of aging and age-related diseases. Furthermore, human sirtuins are considered promising therapeutic targets for anti-aging and ageing-related diseases and have attracted interest in scientific communities to develop small molecule activators or drugs to ameliorate a wide range of ageing disorders. In this review, we also summarize the discovery and development status of sirtuin-targeted drug and further discuss the potential medical strategies of sirtuins in delaying aging and treating age-related diseases.

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    Cell Cycle Deficits in Neurodegenerative Disorders: Uncovering Molecular Mechanisms to Drive Innovative Therapeutic Development
    Joseph Chitra,Mangani Abubakar Siddiq,Gupta Veer,Chitranshi Nitin,Shen Ting,Dheer Yogita,KB Devaraj,Mirzaei Mehdi,You Yuyi,Graham Stuart L,Gupta Vivek
    Aging and disease. 2020, 11 (4): 946-966.   DOI: 10.14336/AD.2019.0923
    Abstract   HTML   PDF (710KB) ( 217 )

    Cell cycle dysregulation has been implicated in the pathogenesis of neurodegenerative disorders. Specialised function obligates neuronal cells to subsist in a quiescent state of cell cycle once differentiated and therefore the circumstances and mechanisms underlying aberrant cell cycle activation in post-mitotic neurons in physiological and disease conditions remains an intriguing area of research. There is a strict requirement of concurrence to cell cycle regulation for neurons to ensure intracellular biochemical conformity as well as interrelationship with other cells within neural tissues. This review deliberates on various mechanisms underlying cell cycle regulation in neuronal cells and underscores potential implications of their non-compliance in neural pathology. Recent research suggests that successful duplication of genetic material without subsequent induction of mitosis induces inherent molecular flaws that eventually assert as apoptotic changes. The consequences of anomalous cell cycle activation and subsequent apoptosis are demonstrated by the increased presence of molecular stress response and apoptotic markers. This review delineates cell cycle events under normal physiological conditions and deficits amalgamated by alterations in protein levels and signalling pathways associated with cell-division are analysed. Cell cycle regulators essentially, cyclins, CDKs, cip/kip family of inhibitors, caspases, bax and p53 have been identified to be involved in impaired cell cycle regulation and associated with neural pathology. The pharmacological modulators of cell cycle that are shown to impart protection in various animal models of neurological deficits are summarised. Greater understanding of the molecular mechanisms that are indispensable to cell cycle regulation in neurons in health and disease conditions will facilitate targeted drug development for neuroprotection.

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    Targeting AMP-Activated Protein Kinase in Aging-Related Cardiovascular Diseases
    Li Tian,Mu Nan,Yin Yue,Yu Lu,Ma Heng
    Aging and disease. 2020, 11 (4): 967-977.   DOI: 10.14336/AD.2019.0901
    Abstract   HTML   PDF (425KB) ( 111 )

    Aging is a pivotal risk factor for developing cardiovascular diseases (CVD) due to the lifelong exposure to various risk factors that may affect the heart and vasculature during aging. AMP-activated protein kinase (AMPK), a serine/threonine protein kinase, is a pivotal endogenous energy regulator that protects against various pathological alterations. In this report, we first introduced the protective mechanisms of AMPK signaling in myocardium, such as oxidative stress, apoptosis, inflammation, autophagy and inflammatory response. Next, we introduced the potential correlation between AMPK and cardiac aging. Then, we highlighted the roles of AMPK signaling in cardiovascular diseases, including myocardial ischemia, cardiomyopathy, and heart failure. Lastly, some potential directions and further perspectives were expanded. The information extends our understanding on the protective roles of AMPK in myocardial aging, which may contribute to the design of drug targets and sheds light on potential treatments of AMPK for aging-related CVD.

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    Potential Biochemical Mechanisms of Brain Injury in Diabetes Mellitus
    Ma Wei-Xing,Tang Jing,Lei Zhi-Wen,Li Chun-Yan,Zhao Li-Qing,Lin Chao,Sun Tao,Li Zheng-Yi,Jiang Ying-Hui,Jia Jun-Tao,Liang Cheng-Zhu,Liu Jun-Hong,Yan Liang-Jun
    Aging and disease. 2020, 11 (4): 978-987.   DOI: 10.14336/AD.2019.0910
    Abstract   HTML   PDF (595KB) ( 163 )

    The goal of this review was to summarize current biochemical mechanisms of and risk factors for diabetic brain injury. We mainly summarized mechanisms published in the past three years and focused on diabetes induced cognitive impairment, diabetes-linked Alzheimer’s disease, and diabetic stroke. We think there is a need to conduct further studies with increased sample sizes and prolonged period of follow-ups to clarify the effect of DM on brain dysfunction. Additionally, we also think that enhancing experimental reproducibility using animal models in conjunction with application of advanced devices should be considered when new experiments are designed. It is expected that further investigation of the underlying mechanisms of diabetic cognitive impairment will provide novel insights into therapeutic approaches for ameliorating diabetes-associated injury in the brain.

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    COVID 19 - Clinical Picture in the Elderly Population: A Qualitative Systematic Review
    Neumann-Podczaska Agnieszka,Al-Saad Salwan R,Karbowski Lukasz M,Chojnicki Michal,Tobis Slawomir,Wieczorowska-Tobis Katarzyna
    Aging and disease. 2020, 11 (4): 988-1008.   DOI: 10.14336/AD.2020.0620
    Abstract   HTML   PDF (792KB) ( 70 )

    The SARS-CoV-2 tendency to affect the older individuals more severely, raises the need for a concise summary isolating this age population. Analysis of clinical features in light of most recently published data allows for improved understanding, and better clinical judgement. A thorough search was performed to collect all articles published from 1st of January to 1st of June 2020, using the keywords COVID-19 and SARS-CoV-2 followed by the generic terms elderly, older adults or older individuals. The quality assessment of studies and findings was performed by an adaptation of the STROBE statement and CERQual approach. Excluding duplicates, a total of 1598 articles were screened, of which 20 studies were included in the final analysis, pertaining to 4965 older COVID-19 patients (≥60 years old). Variety in symptoms was observed, with fever, cough, dyspnea, fatigue, or sputum production being the most common. Prominent changes in laboratory findings consistently indicated lymphopenia and inflammation and in some cases organ damage. Radiological examination reveals ground glass opacities with occasional consolidations, bilaterally, with a possible peripheral tendency. An evident fraction of the elderly population (25.7%) developed renal injury or impairment as a complication. Roughly 71.4% of the older adults require supplementary oxygen, while invasive mechanical ventilation was required in almost a third of the reported hospitalized older individuals. In this review, death occurred in 20.0% of total patients with a recorded outcome (907/4531). Variability in confidence of findings is documented. Variety in symptom presentation is to be expected, and abnormalities in laboratory findings are present. Risk for mortality is evident, and attention to the need for supplementary oxygen and possible mechanical ventilation is advised. Further data is required isolating this age population. Presented literature may allow for the construction of better predictive models of COVID-19 in older populations.

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    Biogenesis, Features, Functions, and Disease Relationships of a Specific Circular RNA: CDR1as
    Guo Ziyuan,Cao Qidong,Zhao Zhuo,Song Chunli
    Aging and disease. 2020, 11 (4): 1009-1020.   DOI: 10.14336/AD.2019.0920
    Abstract   HTML   PDF (508KB) ( 118 )

    In 2011, Hansen discovered the natural antisense transcript (NAT) of the cerebellar degeneration-related protein 1 gene (CDR1), and further described CDR1 NAT as a circular RNA (CircRNA). CDR1 antisense RNA (CDR1as), which is the official name of CDR1 NAT, is conserved and extensively expressed in most eutherian mammal brains and other specialized tissues. Further studies have elucidated its biogenesis, features, functions, and relationships with diseases. CDR1as is involved in many disease processes as a microRNA (miR) sponge. Therefore, it seems that further research on CDR1as could facilitate the diagnosis and treatment of some diseases, such as cancer and diabetes. However, a detailed analysis of the results of studies on CDR1as revealed that they are inconsistent and make unclear conclusions. In this review, we gathered and analyzed the recent studies about CDR1as in detail and aimed to elucidate accurate conclusions from them.

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Kunlin Jin, M.D., Ph.D., Professor
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