Age-Induced Reduction in Mitochondrial Manganese Superoxide Dismutase Activity and Tolerance of Macrophages Against Apoptosis Induced by Oxidized Low Density Lipoprotein

Fujimoto, Hajime; Kobayashi, Hill Hiroki; Ohno, Minoru

doi:10.1253/circj.cj-09-0491

Cited by 33 publications

(21 citation statements)

References 30 publications

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“…Whereas gradual loss of mitochondrial function occurs with age, it can be accelerated by oxidative stress, for example due to increased oxidized LDL (oxLDL) during atherogenesis. 64,65 …”

Section: Dna Damagementioning

confidence: 99%

Aging and Atherosclerosis

Wang

Bennett

2012

Circulation Research

717

323

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Atherosclerosis is classed as a disease of aging, such that increasing age is an independent risk factor for the development of atherosclerosis. Atherosclerosis is also associated with premature biological aging, as atherosclerotic plaques show evidence of cellular senescence characterized by reduced cell proliferation, irreversible growth arrest and apoptosis, elevated DNA damage, epigenetic modifications, and telomere shortening and dysfunction. Not only is cellular senescence associated with atherosclerosis, there is growing evidence that cellular senescence promotes atherosclerosis. This review examines the pathology of normal vascular aging, the evidence for cellular senescence in atherosclerosis, the mechanisms underlying cellular senescence including reactive oxygen species, replication exhaustion and DNA damage, the functional consequences of vascular cell senescence, and the possibility that preventing accelerated cellular senescence is a therapeutic target in atherosclerosis.

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“…Whereas gradual loss of mitochondrial function occurs with age, it can be accelerated by oxidative stress, for example due to increased oxidized LDL (oxLDL) during atherogenesis. 64,65 …”

Section: Dna Damagementioning

confidence: 99%

Aging and Atherosclerosis

Wang

Bennett

2012

Circulation Research

717

323

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“…Extensively oxidized proteins become irreversibly aggregated and are degraded through aggrephagy, a selective form of macroautophagy. In aged cells of the immune system, there is an increased level of free radicals[109], a decreased level/function of enzymes involved in clearing free radicals[110] which participate in compromising phagocytosis, proteasomal activity and TLR signaling[19,69,111]. Recently, Cannizo et al [112] showed that DCs isolated from the spleen and lymph nodes as well as the CD34 + bone marrow precursors of old mice accumulate oxidatively modified proteins with side chain carbonylation, advanced glycation end products and lipid peroxidation, and that endosomal accumulation of oxidatively modified proteins interferes with the efficient processing of exogenous antigens and degradation of macroautophagy delivered proteins.…”

Section: Pulmonary Responsementioning

confidence: 99%

Immunosenescence in monocytes, macrophages, and dendritic cells: Lessons learned from the lung and heart

Linton

Thoman

2014

Immunology Letters

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In the absence of an immune challenge, healthy, aged individuals have a significantly higher basal inflammatory state where circulating levels of cytokines, including IL-6, TNF-α and IL-1β, are elevated[1]. This progressive pro-inflammatory state, termed “inflamm-aging,” affects the phenotype/function of cells present in the aged as well as renders the older individuals more susceptible to a poor prognosis after systemic insults. Although it is important to understand the mechanisms that underlie the progression of disease, most preclinical analyses of disease therapies are performed in young adult mice that have an intact, functional immune system. Oftentimes, this is not necessarily representative of the immune disposition in the aged, let alone diseased, aged. Herein, two distinct responses that are not only commonly associated with aging but that also have dendritic cells and/or monocytes and macrophages as key players are discussed: pulmonary infection and myocardial infarction. Although studies of pulmonary infection in the aged have progressed significantly, studies of monocytes and macrophages in inflammation and cardiac injury following ischemia in the aged have not been as forthcoming. Nonetheless, several elegant studies have established the dynamic role of monocytes and macrophages post infarction. These will be discussed in light of what is known with aging.

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“…AGE induced cell death is partially blocked by Ab treatment aimed at blocking the AGE receptor as well as anti-apoptotic drugs and antioxidants [77]. Similarly, studies in cultured macrophages indicated a positive correlation between exposure to oxidized low-density lipoproteins and cell death [60]. Additionally, exposure of macrophages to serum glycated proteins such as pentosidine, a well-characterized AGE found in plasma and tissue of diabetic and uremic subjects also induces apoptotic cell death [78].…”

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confidence: 99%

“…Additionally, levels of superoxide dismutase, catalase and glutathione peroxidase, the enzymes in charge of free radical clearance in the cytosol, are decreased in aging cells [59]. Likewise, the manganese superoxide dismutase, an antioxidant enzyme located in the mitochondria, which protects macrophages from apoptosis induced by oxidized LDL, is also decreased in aging macrophages [60], all contributing to the increased cellular oxidative stress [58,59]. The observed oxidative post-translational modifications occurring on different biomolecules have been reported to compromise the functionality of subcellular organelles, compartments and membranes.…”

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confidence: 99%