Search results for "cellular senescence"
showing 10 items of 109 documents
Ovarian senescence increases liver fibrosis in humans and zebrafish with steatosis
2015
ABSTRACT Contrasting data exist on the effect of gender and menopause on the susceptibility, development and liver damage progression in non-alcoholic fatty liver disease (NAFLD). Our aim was to assess whether menopause is associated with the severity of liver fibrosis in individuals with NAFLD and to explore the issue of ovarian senescence in experimental liver steatosis in zebrafish. In 244 females and age-matched males with biopsy-proven NAFLD, we assessed anthropometric, biochemical and metabolic features, including menopausal status (self-reported); liver biopsy was scored according to ‘The Pathology Committee of the NASH Clinical Research Network’. Young and old male and female zebraf…
Calorie Restriction in Adulthood Reduces Hepatic Disorders Induced by Transient Postnatal Overfeeding in Mice
2019
International audience; Impaired early nutrition influences the risk of developing metabolic disorders in later life. We observed that transient postnatal overfeeding (OF) in mice induces long-term hepatic alterations, characterized by microsteatosis, fibrosis associated with oxidative stress (OS), and stress-induced premature senescence (SIPS). In this study, we investigated whether such changes can be reversed by moderate calorie restriction (CR). C57BL/6 male mice pups were maintained during lactation in litters adjusted to nine pups in the normal feeding (NF) group and three pups in the transient postnatal OF group. At six months of age, adult mice from the NF and OF groups were randoml…
Is the Mean Blood Leukocyte Telomere Length a Predictor for Sporadic Thoracic Aortic Aneurysm? Data from a Preliminary Study
2012
Telomeres have been postulated as a universal clock that shortens in parallel with cellular aging. They are specialized DNA-protein structures at the ends of chromosome with remarkable functions--preventing their recognition as double-stranded DNA breaks, protecting their recombination and degradation, and avoiding a DNA damage cellular response. Telomere shortening is currently considered the best aging marker, but is also a predictor for age-related diseases, including cardiovascular diseases. Biological age clearly seems to be a better predictor of vascular risk rather than chronological age. This concept is supported by key assumptions that peripheral blood leukocyte telomere content ac…
Sustained telomere erosion due to increased stem cell turnover during triple autologous hematopoietic stem cell transplantation.
2007
Telomeres cap chromosomal ends and are shortened throughout a lifetime. Additional telomere erosion has been documented during conventional chemotherapy or hematopoietic stem cell transplantation. Previous studies of stem cell transplantation reported variable amounts of telomere shortening with inconsistent results regarding the persistence of telomere shortening. Here we have prospectively studied telomere length and proliferation kinetics of hematopoietic cells in aggressive non-Hodgkin lymphoma patients who underwent a four-course high-dose chemotherapy protocol combined with triple autologous stem cell transplantation. We observed sustained telomere shortening in hematopoietic cells af…
Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mtor pathways in controlling growth and sensitivity to therapy-implications for cancer and aging
2011
Dysregulated signaling through the Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways is often the result of genetic alterations in critical components in these pathways or upstream activators. Unrestricted cellular proliferation and decreased sensitivity to apoptotic-inducing agents are typically associated with activation of these pro-survival pathways. This review discusses the functions these pathways have in normal and neoplastic tissue growth and how they contribute to resistance to apoptotic stimuli. Crosstalk and commonly identified mutations that occur within these pathways that contribute to abnormal activation and cancer growth will also be addressed. Finally the recently described …
Quiescence Modulates Stem Cell Maintenance and Regenerative Capacity in the Aging Brain.
2018
The function of somatic stem cells declines with age. Understanding the molecular underpinnings of this decline is key to counteract age-related disease. Here, we report a dramatic drop in the neural stem cells (NSCs) number in the aging murine brain. We find that this smaller stem cell reservoir is protected from full depletion by an increase in quiescence that makes old NSCs more resistant to regenerate the injured brain. Once activated, however, young and old NSCs show similar proliferation and differentiation capacity. Single-cell transcriptomics of NSCs indicate that aging changes NSCs minimally. In the aging brain, niche-derived inflammatory signals and the Wnt antagonist sFRP5 induce…
Consequences on offspring of abnormal function in ageing gametes.
2000
The present review aims to analyse (i) the molecular, biochemical and cellular changes that accompany oocyte and sperm ageing in any of the internal or external environments where they can reside, and (ii) the consequences of the abnormal function in ageing gametes on pre- and post-implantation development and later life of offspring. This review also aims to propose and discuss cellular/molecular mechanisms framed within the 'free radical theory of ageing'. It appears that the ageing of gametes prior to fertilization may affect many molecular, biochemical and cellular pathways that may jeopardize not only pre- and post-implantation embryo/fetal development but also later life of offspring.…
Intrinsically determined cell death of developing cortical interneurons.
2009
The cell death of inhibitory neurons, which originate far from the cortical areas to which they migrate during embryonic development, is determined autonomously rather than by competition for trophic signals from other cell types. It has long been known that apoptosis, a form of programmed cell death, eliminates young cells from developing tissues. In the field of neurobiology, it is widely believed that developmental neuronal-cell death results from cellular competition for environmentally derived survival signals that selects for an optimally sized and properly wired population of neurons. This study of developmental cell death in the mouse cortex in vivo, in vitro and after transplantati…
Functional characterization of the dural sinuses as a neuroimmune interface
2021
Summary Despite the established dogma of central nervous system (CNS) immune privilege, neuroimmune interactions play an active role in diverse neurological disorders. However, the precise mechanisms underlying CNS immune surveillance remain elusive; particularly, the anatomical sites where peripheral adaptive immunity can sample CNS-derived antigens and the cellular and molecular mediators orchestrating this surveillance. Here, we demonstrate that CNS-derived antigens in the cerebrospinal fluid (CSF) accumulate around the dural sinuses, are captured by local antigen-presenting cells, and are presented to patrolling T cells. This surveillance is enabled by endothelial and mural cells formin…
Physiology of the aging bone and mechanisms of action of bisphosphonates.
2011
Fragility fractures, a major public health concern, are expected to further increase due to aging of the world populations because age remains a cardinal, independent determinant of fracture risk. With aging the balance between bone formation and resorption during the remodeling process becomes negative, with increased resorption and reduced formation. Bisphosphonates (BPs) are widely prescribed anti-resorptive agents that inhibit osteoclasts attachment to bone matrix and enhance osteoclast apoptosis. BPs can be divided into nitrogen-containing (N-BPs) and non-nitrogen-containing BPs (non-N-BPs). Both classes induce apoptosis but they evoke it differently. Several studies have examined the …