Advances and challenges in geroscience research: An update

Aging remains the most pervasive risk factor for a wide range of chronic diseases that afflict modern societies. In the United States alone, incidence of age-related diseases (e.g., cardiovascular disease, stroke, Alzheimer’s disease, vascular cognitive impairment and dementia, cancer, hypertension, type-2 diabetes, chronic obstructive pulmonary disease, and osteoarthritis) is on the rise, posing an unsustainable socioeconomic burden even for the most developed countries. Tackling each and every age-related disease alone is proving to be costly and ineffective. The emerging field of geroscience has posed itself as an interdisciplinary approach that aims to understand the relationship between the biology of aging and the pathophysiology of chronic age-related diseases. According to the geroscience concept, aging is the single major risk factor that underlies several age-related chronic diseases, and manipulation of cellular and systemic aging processes can delay the manifestation and/or severity of these age-related chronic pathologies. The goal of this endeavor is to achieve health improvements by preventing/delaying the pathogenesis of several age-related diseases simultaneously in the elderly population by targeting key cellular and molecular processes of aging instead of managing diseases of aging as they arise individually. In this review, we discuss recent advances in the field of geroscience, highlighting their implications for potential future therapeutic targets and the associated scientific challenges and opportunities that lay ahead

Exposome and unhealthy aging: environmental drivers from air pollution to occupational exposures

The aging population worldwide is facing a significant increase in age-related non-communicable diseases, including cardiovascular and brain pathologies. This comprehensive review paper delves into the impact of the exposome, which encompasses the totality of environmental exposures, on unhealthy aging. It explores how environmental factors contribute to the acceleration of aging processes, increase biological age, and facilitate the development and progression of a wide range of age-associated diseases. The impact of environmental factors on cognitive health and the development of chronic age-related diseases affecting the cardiovascular system and central nervous system is discussed, with a specific focus on Alzheimer’s disease, Parkinson’s disease, stroke, small vessel disease, and vascular cognitive impairment (VCI). Aging is a major risk factor for these diseases. Their pathogenesis involves cellular and molecular mechanisms of aging such as increased oxidative stress, impaired mitochondrial function, DNA damage, and inflammation and is influenced by environmental factors. Environmental toxicants, including ambient particulate matter, pesticides, heavy metals, and organic solvents, have been identified as significant contributors to cardiovascular and brain aging disorders. These toxicants can inflict both macro- and microvascular damage and many of them can also cross the blood–brain barrier, inducing neurotoxic effects, neuroinflammation, and neuronal dysfunction. In conclusion, environmental factors play a critical role in modulating cardiovascular and brain aging. A deeper understanding of how environmental toxicants exacerbate aging processes and contribute to the pathogenesis of neurodegenerative diseases, VCI, and dementia is crucial for the development of preventive strategies and interventions to promote cardiovascular, cerebrovascular, and brain health. By mitigating exposure to harmful environmental factors and promoting healthy aging, we can strive to reduce the burden of age-related cardiovascular and brain pathologies in the aging population

Electroconvulsive therapy added to non-clozapine antipsychotic medication for treatment resistant schizophrenia: Meta-analysis of randomized controlled trials

This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of the combination of electroconvulsive therapy (ECT) and antipsychotic medication (except for clozapine) versus the same antipsychotic monotherapy for treatment-resistant schizophrenia (TRS). Two independent investigators extracted data for a random effects meta-analysis and pre-specified subgroup and meta-regression analyses. Weighted and standard mean difference (WMD/SMD), risk ratio (RR) ±95% confidence intervals (CIs), number needed to treat (NNT), and number needed to harm (NNH) were calculated. Eleven studies (n = 818, duration = 10.2±5.5 weeks) were identified for meta-analysis. Adjunctive ECT was superior to antipsychotic monotherapy regarding (1) symptomatic improvement at last-observation endpoint with an SMD of -0.67 (

CB2-receptor stimulation attenuates TNF-alpha-induced human endothelial cell activation, transendothelial migration of monocytes, and monocyte-endothelial adhesion.

Targeting cannabinoid-2 (CB(2)) receptors with selective agonists may represent a novel therapeutic avenue in various inflammatory diseases, but the mechanisms by which CB(2) activation exerts its anti-inflammatory effects and the cellular targets are elusive. Here, we investigated the effects of CB(2)-receptor activation on TNF-alpha-induced signal transduction in human coronary artery endothelial cells in vitro and on endotoxin-induced vascular inflammatory response in vivo. TNF-alpha induced NF-kappaB and RhoA activation and upregulation of adhesion molecules ICAM-1 and VCAM-1, increased expression of monocyte chemoattractant protein, enhanced transendothelial migration of monocytes, and augmented monocyte-endothelial adhesion. Remarkably, all of the above-mentioned effects of TNF-alpha were attenuated by CB(2) agonists. CB(2) agonists also decreased the TNF-alpha- and/or endotoxin-induced ICAM-1 and VCAM-1 expression in isolated aortas and the adhesion of monocytes to aortic vascular endothelium. CB(1) and CB(2) receptors were detectable in human coronary artery endothelial cells by Western blotting, RT-PCR, real-time PCR, and immunofluorescence staining. Because the above-mentioned TNF-alpha-induced phenotypic changes are critical in the initiation and progression of atherosclerosis and restenosis, our findings suggest that targeting CB(2) receptors on endothelial cells may offer a novel approach in the treatment of these pathologies

Influence of hyperhomocysteinemia on the cellular redox state - Impact on homocysteine-induced endothelial dysfunction

Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis. An increasing body of evidence has implicated oxidative stress as being contributory to homocysteines deleterious effects on the vasculature. Elevated levels of homocysteine may lead to increased generation of superoxide by a biochemical mechanism involving nitric oxide synthase, and, to a lesser extent, by an increase in the chemical oxidation of homocysteine and other aminothiols in the circulation. The resultant increase in superoxide levels is further amplified by homocysteinedependent alterations in the function of cellular antioxidant enzymes such as cellular glutathione peroxidase or extracellular superoxide dismutase. One direct clinical consequence of elevated vascular superoxide levels is the inactivation of the vasorelaxant messenger nitric oxide, leading to endothelial dysfunction. Scavenging of superoxide anion by either superoxide dismutase or 4,5-dihydroxybenzene 1,3-disulfonate (Tiron) reverses endothelial dysfunction in hyperhomocysteinemic animal models and in isolated aortic rings incubated with homocysteine. Similarly, homocysteineinduced endothelial dysfunction is also reversed by increasing the concentration of the endogenous antioxidant glutathione or overexpressing cellular glutathione peroxidase in animal models of mild hyperhomocysteinemia. Taken together, these findings strongly suggest that the adverse vascular effects of homocysteine are at least partly mediated by oxidative inactivation of nitric oxide

Obesity-induced cognitive impairment in older adults: a microvascular perspective

Over two-thirds of individuals aged 65 and older are obese or overweight in the United States. Epidemiological data show an association between the degree of adiposity and cognitive dysfunction in the elderly. In this review, the pathophysiological roles of microvascular mechanisms, including impaired endothelial function and neurovascular coupling responses, microvascular rarefaction, and blood-brain barrier disruption in the genesis of cognitive impairment in geriatric obesity are considered. The potential contribution of adipose-derived factors and fundamental cellular and molecular mechanisms of senescence to exacerbated obesity-induced cerebromicrovascular impairment and cognitive decline in aging are discussed

The disability rate of 5-year post-stroke and its correlation factors: A national survey in China

Few studies on long-term functional outcome have been conducted in post-stroke patients in China. The objective of this study was to conduct a nationwide survey in China to investigate the 5-year prevalence of post-stroke disability and its correlation factors. A total of 893 patients with ischemic stroke were included. Demographic, clinical and neuro-imaging information were collected with standardized instruments that assessed stroke severity, depression, cognitive impairment, stroke recurrence and physical disability. Disability was assessed with the modified Ranking Score (mRS), of which a cutoff score _2 indicates disability. Statistical analysis included chi-square tests, two independent samples t-tests, Mann-Whitney U test and multiple logistic regression analysis. The frequency of disability in this study population was 45%. Multivariate analyses revealed that older age, lower education level, previous history of stroke, stroke severity at admission, depression, cognitive impairment at 3 months, and stroke recurrence within 5 years follow up were all significantly associated with post-stroke disability. The disability rate in 5-year post-stroke was high in Chinese patients. Treatment of depression, s

Biochemical parameters of silver catfish (Rhamdia quelen) after transport with eugenol or essential oil of Lippia alba added to the water

The transport of live fish is a routine practice in aquaculture and constitutes a considerable source of stress to the animals. The addition of anesthetic to the water used for fish transport can prevent or mitigate the deleterious effects of transport stress. This study investigated the effects of the addition of eugenol (EUG) (1.5 or 3.0 mu L L-1) and essential oil of Lippia alba (EOL) (10 or 20 mu L L-1) on metabolic parameters (glycogen, lactate and total protein levels) in liver and muscle, acetylcholinesterase activity (AChE) in muscle and brain, and the levels of protein carbonyl (PC), thiobarbituric acid reactive substances (TBARS) and nonprotein thiol groups (NPSH) and activity of glutathione-S-transferase in the liver of silver catfish (Rhamdia quelen; Quoy and Gaimard, 1824) transported for four hours in plastic bags (loading density of 169.2 g L-1). The addition of various concentrations of EUG (1.5 or 3.0 mu L L-1) and EOL (10 or 20 mu L L-1) to the transport water is advisable for the transportation of silver catfish, since both concentrations of these substances increased the levels of NPSH antioxidant and decreased the TBARS levels in the liver. In addition, the lower liver levels of glycogen and lactate in these groups and lower AChE activity in the brain (EOL 10 or 20 mu L L-1) compared to the control group indicate that the energetic metabolism and neurotransmission were lower after administration of anesthetics, contributing to the maintenance of homeostasis and sedation status.Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS/PRONEX) [10/0016-8]; Conselho Nacional de Pesquisa e Desenvolvimento Cientifico (CNPq) [470964/2009-0]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); CNPqinfo:eu-repo/semantics/publishedVersio

Role of NAD(P)H Oxidase in Superoxide Generation and Endothelial Dysfunction in Goto-Kakizaki (GK) Rats as a Model of Nonobese NIDDM

Background: Cardiovascular disease is the leading cause of mortality in diabetics, and it has a complex etiology that operates on several levels. Endothelial dysfunction and increased generation of reactive oxygen species are believed to be an underlying cause of vascular dysfunction and coronary artery disease in diabetes. This impairment is likely the result of decreased bioavailability of nitric oxide (NO) within the vasculature. However, it is unclear whether hyperglycemia per se stimulates NADPH oxidase-derived superoxide generation in vascular tissue. Methods and Results: This study focused on whether NADPH oxidase-derived superoxide is elevated in vasculature tissue evoking endothelial/smooth muscle dysfunction in the hyperglycemic (16964 mg%) Goto-Kakizaki (GK) rat. By dihydroethidine fluorescence staining, we determined that aorta superoxide levels were significantly elevated in 9 month-old GK compared with age matched Wistar (GK; 19566%, Wistar; 10063.5%). Consistent with these findings, 10 26 mol/L acetylcholine-induced relaxation of the carotid artery was significantly reduced in GK rats compared with age matched Wistar (GK; 4167%, Wistar; 10065%) and measurements in the aorta showed a similar trend (p =.08). In contrast, relaxation to the NO donor SNAP was unaltered in GK compared to Wistar. Endothelial dysfunction was reversed by lowering of superoxide with apocynin, a specific Nox inhibitor. Conclusions: The major findings from this study are that chronic hyperglycemia induces significant vascular dysfunction i

New species longevity record for the northern quahog (=hard clam), Mercenaria mercenaria

Author Posting. © National Shellfisheries Association, 2011. This article is posted here by permission of National Shellfisheries Association for personal use, not for redistribution. The definitive version was published in Journal of Shellfish Research 30 (2011): 35-38, doi:10.2983/035.030.0106.Twenty-two large shells (>90 mm shell height) from a sample of live collected hard shell clams, Mercenaria mercenaria, from Buzzards Bay, Woods Hole, Cape Cod, MA, were subjected to sclerochronological analysis. Annually resolved growth lines in the hinge region and margin of the shell were identified and counted; the age of the oldest clam shell was determined to be at least 106 y. This age represents a considerable increase in the known maximum life span for M. mercenaria, more than doubling the maximum recorded life span of the species (46 y). More than 85% of the clam shells aged had more than 46 annual increments, the previous known maximum life span for the species. In this article we present growth rate and growth performance indicators (the overall growth performance and phi prime) for this record-breaking population of M. mercenaria. Recently discovered models of aging require accurate age records and growth parameters for bivalve populations if they are to be utilized to their full potential.This work was supported by grants from the American Diabetes Association (to Z. U.), American Federation for Aging Research (to A. C.), the University of Oklahoma College of Medicine Alumni Association (to A. C.), the BBSRC (to C. A. R.),the National Institutes of Health (AT006526 and HL077256 to Z. U.; AG022873 and AG025063 to S. N. A.), and the DFG Cluster of Excellence ‘‘Future Ocean’’ (to E. P.)