Search results for "Sirtuin"
showing 10 items of 67 documents
Interventions to Slow Aging in Humans: Are We Ready?
2015
The workshop entitled 'Interventions to Slow Aging in Humans: Are We Ready?' was held in Erice, Italy, on October 8-13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consens…
Genetic manipulation of longevity-related genes as a tool to regulate yeast life span and metabolite production during winemaking
2013
Abstract Background Yeast viability and vitality are essential for different industrial processes where the yeast Saccharomyces cerevisiae is used as a biotechnological tool. Therefore, the decline of yeast biological functions during aging may compromise their successful biotechnological use. Life span is controlled by a variety of molecular mechanisms, many of which are connected to stress tolerance and genomic stability, although the metabolic status of a cell has proven a main factor affecting its longevity. Acetic acid and ethanol accumulation shorten chronological life span (CLS), while glycerol extends it. Results Different age-related gene classes have been modified by deletion or o…
Moderate weight loss attenuates chronic endoplasmic reticulum stress and mitochondrial dysfunction in human obesity
2018
Abstract Objective In obese patients undergoing caloric restriction, there are several potential mechanisms involved in the improvement of metabolic outcomes. The present study further explores whether caloric restriction can modulate endoplasmic reticulum (ER) stress and mitochondrial function, as both are known to be mechanisms underlying inflammation and insulin resistance (IR) during obesity. Methods A total of 64 obese patients with BMI ≥35 kg/m2 underwent a dietary program consisting of 6 weeks of a very-low-calorie diet followed by 18 weeks of low-calorie diet. We evaluated changes in the metabolic and inflammatory markers -TNFα, hsCRP, complement component 3 (C3c), and retinol bindi…
Conserved role of Ras-GEFs in promoting aging: from yeast to mice
2011
RasGRF1 is a Ras-guanine nucleotide exchange factor implicated in a variety of physiological processes including learning and memory and glucose homeostasis. To determine the role of RASGRF1 in aging, lifespan and metabolic parameters were analyzed in aged RasGrf1(-/-) mice. We observed that mice deficient for RasGrf1(-/-) display an increase in average and most importantly, in maximal lifespan (20% higher than controls). This was not due to the role of Ras in cancer because tumor-free survival was also enhanced in these animals. Aged RasGrf1(-/-) displayed better motor coordination than control mice. Protection against oxidative stress was similarly preserved in old RasGrf1(-/-). IGF-I lev…
SARS CoV2 infection _The longevity study perspectives
2021
Graphical abstract
Polychlorinated biphenyls affect histone modification pattern in early development of rats: a role for androgen receptor-dependent modulation?
2012
Background: The epigenome represents an important target of environmental pollution. Early-life exposure to polychlorinated biphenyls (PCBs) modifies sex steroid enzymes and receptor transcription patterns. Steroid receptors, such as androgen receptor (AR), function as coregulators of histone modification enzymes. Aim: To clarify if a PCB early-life exposure might affect the epigenome in rat liver, we analyzed some histone post-translational modifications (H3K4me3 and H4K16Ac) and the corresponding histone remodeling enzymes, and the AR as a histone enzyme coregulator. Results: We observed a decrease of H4K16Ac and H3K4me3 levels, possibly linked to the induction of chromatin-modifying enz…
Muscle NAD+ depletion and Serpina3n as molecular determinants of murine cancer cachexia—the effects of blocking myostatin and activins
2020
Objective Cancer cachexia and muscle loss are associated with increased morbidity and mortality. In preclinical animal models, blocking activin receptor (ACVR) ligands has improved survival and prevented muscle wasting in cancer cachexia without an effect on tumour growth. However, the underlying mechanisms are poorly understood. This study aimed to identify cancer cachexia and soluble ACVR (sACVR) administration-evoked changes in muscle proteome. Methods Healthy and C26 tumour-bearing (TB) mice were treated with recombinant sACVR. The sACVR or PBS control were administered either prior to the tumour formation or by continued administration before and after tumour formation. Muscles were an…
Free [NADH]/[NAD+] regulates sirtuin expression
2011
Sirtuins are deacetylases involved in metabolic regulation and longevity. Our aim was to test the hypothesis that they are subjected to redox regulation by the [NADH]/[NAD(+)] ratio. We used NIH3T3 fibroblasts in culture, Drosophila fed with or without ethanol and exercising rats. In all three models an increase in [NADH]/[NAD(+)] came up with an increased expression of sirtuin mRNA and protein. PGC-1α (a substrate of sirtuins) protein level was significantly increased in fibroblasts incubated with lactate and pyruvate but this effect was lost in fibroblasts obtained from sirtuin-deficient mice. We conclude that the expression of sirtuins is subject to tight redox regulation by the [NADH]/[…
Mitochondrial biogenesis fails in secondary biliary cirrhosis in rats leading to mitochondrial DNA depletion and deletions
2011
Chronic cholestasis is characterizedby mitochondrial dysfunction, associated with loss of mitochondrialmembrane potential, decreased activities of respiratory chaincomplexes, and ATP production. Our aim was to determine themolecular mechanisms that link long-term cholestasis to mitochondrialdysfunction. We studied a model of chronic cholestasis inducedby bile duct ligation in rats. Key sensors and regulators of theenergetic state and mitochondrial biogenesis, mitochondrial DNA(mtDNA)-to-nuclear DNA (nDNA) ratio (mtDNA/nDNA) relativecopy number, mtDNA deletions, and indexes of apoptosis (BAX,BCL-2, and cleaved caspase 3) and cell proliferation (PCNA) wereevaluated. Our results show that long…
Different Patterns of Lung Sirtuin Expression in Smokers With and Without Chronic Obstructive Pulmonary Disease
2012
Background and Objective. Chronic obstructive pulmonary disease is characterized by persistent and modified inflammatory responses in lung. Human sirtuin, an antiaging and antiinflammatory protein, is a metabolic NAD(+)-dependent protein/histone deacetylase that regulates proinflammatory mediators by deacetylating histone and nonhistone proteins. The aim of our study was to compare the expression of sirtuin in large and small airways in nonsmokers, asymptomatic smokers, and smokers with chronic obstructive pulmonary disease. Material and Methods. A total of 12 nonsmokers, 14 asymptomatic smokers, and 12 smokers with moderate chronic obstructive pulmonary disease were enrolled into the study…