Search results for "CHON"
showing 10 items of 1866 documents
Hsp60 and human aging: Les liaisons dangereuses
2013
Stressors can cause abnormal intracellular accumulation of Hsp60 and its localization in extramitochondrial sites, secretion, and circulation, with immune system activation. Dysfunction of chaperones associated with their quantitative and qualitative decline with aging (chaperonopathies of aging) characterizes senescence and is a potential causal factor in the physiological deterioration that occurs with it. The role of Hsp60 in aging is not easy to elucidate, because aging is accompanied by pathologies (e.g., cardiovascular and neurodegenerative disorders, osteoporosis, diabetes, cancer, etc.) in which Hsp60 has been implicated but, although those disorders are more frequent in the elderly…
Depletion of cytosolic GSH decreases the ATP levels and viability of synaptosomes from aged mice but not from young mice
1995
The effect of glutathione depletion on the viability of freshly isolated synaptosomes from whole brain was investigated in young and aged mice. Aging did not influence the GSH and ATP levels and the viability of these synaptosomes. However depletion of glutathione caused by the cytosolic glutathione inhibitor diethyl maleate (1 mM) resulted in a significant decline, after 60 min of incubation, in ATP levels and viability in the synaptosomes from aged mice but not in those from young mice. When synaptosomes were incubated in the presence of the mitochondrial glutathione inhibitor ethacrynic acid (0.2 mM) there was a similar decline in glutathione, ATP levels and synaptosomal viability, both …
Senescence-associated HSP60 expression in normal human skin fibroblasts
2005
Normal mammalian fibroblasts cultured in vitro undergo a limited number of divisions before entering a senescent phase in which they can be maintained for long periods but cannot be induced to divide. Senescent cells become unresponsive to growth-promoting signals and exhibit senescent cell morphology with flattened and enlarged cell shape. Several chaperones have a direct effect on cellular senescence. HSP60 has been largely studied in our laboratories and it has been associated with uncontrolled cell proliferation in tumor cells. Since senescence is firmly regulated during cell cycle progression, we wanted to investigate HSP60 protein level during cellular senescence. Our data show that H…
Long-term effects of delayed parenthood.
1998
The present study aims to define, characterize and compare the long-term effects on offspring of delayed parenthood. Data published so far on this topic show that maternal and paternal ageing may affect offspring by different mechanisms. Delayed motherhood is characterized by increased probability of obstetric complications and/or fetal and perinatal problems which, in turn, may increase the risks of mortality and morbidity in newborns and later life. Furthermore, maternal ageing is distinguished by a decreased ratio of male to female infants and higher odds of conceiving a trisomic child and/or an individual suffering from mitochondrial DNA disorders. In contrast, delayed fatherhood is ass…
The role of mitochondrial oxidative stress in aging.
2003
Mitochondria are both a major source of oxidants and a target for their damaging effects, and, therefore, mitochondrial oxidative stress appears to be a cause, rather than a consequence, of cell aging. Oxidative damage in aging is particularly high in specific molecular targets, such as mitochondrial DNA and aconitase, and mitochondrial oxidative stress may drive tissue aging through intrinsic apoptosis. Mitochondrial function and morphology are impaired upon aging, as judged by a decline in membrane potential as well as by an increase in peroxide production and size of the organelles. In view of the age-related decreases in mitochondrial protein synthesis, mitochondrial transcripts, and ex…
Causes and Consequences of Damage to Mitochondria: Study of Functional Aspects by Flow Cytometry
2003
A rapidly increasing amount of data supports the view that progressive bioenergetic loss caused by injury of the main energy-producing subcellular organelles, that is, the mitochondria, plays a key role in aging. A link between senescence and energy loss is already implied in Harman's (1) free radical theory of aging, according to which oxygen-derived free radicals injure the cells, with concomitant impairment of performance at the cellular and physiological levels. Further, Miquel and co-workers (2, 3) have proposed a mitochondrial theory of aging, according to which aging results from oxygen stress damage to the mitochondrial genome, with concomitant bioenergetic decline. More recently, a…
The role of telomeres and telomerase in the senescence of postmitotic cells
2020
Senescence is a process related to the stopping of divisions and changes leading the cell to the SASP phenotype. Permanent senescence of many SASP cells contributes to faster aging of the body and development of age-related diseases due to the release of pro-inflammatory factors. Both mitotically active and non-dividing cells can undergo senescence as a result of activation of different molecular pathways. Telomeres, referred to as the molecular clock, direct the dividing cell into the aging pathway when reaching a critical length. In turn, the senescence of postmitotic cells depends not on the length of telomeres, but their functionality. Dysfunctional telomeres are responsible for trigger…
BCL-xL, a Mitochondrial Protein Involved in Successful Aging: From C. elegans to Human Centenarians
2020
B-Cell Lymphoma-extra-large (BCL-xL) is involved in longevity and successful aging, which indicates a role for BCL-xL in cell survival pathway regulation. Beyond its well described role as an inhibitor of apoptosis by preventing cytochrome c release, BCL-xL has also been related, indirectly, to autophagy and senescence pathways. Although in these latter cases, BCL-xL has dual roles, either activating or inhibiting, depending on the cell type and the specific conditions. Taken together, all these findings suggest a precise mechanism of action for BCL-xL, able to regulate the crosstalk between apoptosis, autophagy, and senescence, thus promoting cell survival or cell death. All three pathways…
NECAB2 participates in an endosomal pathway of mitochondrial stress response at striatal synapses
2021
Synaptic signaling depends on ATP generated by mitochondria. Due to extensive connectivity, the striatum is especially vulnerable to mitochondrial dysfunction and thus requires efficient mitochondrial quality control. We found that the neuronal calcium-binding protein NECAB2 ensures synaptic function in the striatum by increasing mitochondrial efficiency. NECAB2 associates with early endosomes and mitochondria at striatal synapses. Loss of NECAB2 dysregulates proteins of the endosomal ESCRT machinery and oxidative phosphorylation. Mitochondria from NECAB2-deficient mice are more abundant but less efficient. These mitochondria exhibit increased respiration and superoxide production but produ…
Influence of retinol on human chondrocytes in agarose culture
1992
Vitamin A and its congeners, collectively called retinoids, are known to have teratogenic potential and have induced craniofacial and limb malformations in numerous animal species. More importantly, retinoids are recognized as teratogenic to fetuses of pregnant women who have taken such preparations for dermatologic disorders. Information gathered from the study of animal models suggests that retinoids interfere with cartilage differentiation. If chondrogenesis in limb development is disturbed it may contribute to limb reductions and malformations. In vitro studies using various animal systems have shown that cartilage matrix macromolecules are altered to resemble those secreted by mesenchy…