Growing cells at 40% ambient oxygen conditions them to subsequent oxidative stress

Brunk, Ulf T.

doi:10.1007/s10522-007-9091-9

Cited by 3 publications

(3 citation statements)

References 9 publications

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“…2007); dietary restriction (Cypser, Tedesco & Johnson 2006); a variety of drugs and pathogens (Murado & Váquez 2007) or ionizing radiation (Parsons 2000; Moskalev 2007). Recent work (Brunk 2007) shows that growing cells in 40% ambient oxygen (an extremely high level of oxygen) conditions them to resist subsequent oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Environment, damage and senescence: modelling the life‐history consequences of variable stress and caloric intake

Mangel¹

2008

Functional Ecology

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Summary 1.Senescence is intimately connected with physiological state, which is affected by the environment. Two aspects of the environment -stress and caloric intake -are investigated in the context of senescence, particularly in the context of repair of damage caused by endogenous and exogenous stressors. 2. In a simple life-history model, the organism is characterized by size (affecting reproductive success) and accumulated damage (affecting survival) at age. The modelled organism experiences an imprinting period, at the end of which it estimates the level of food and damaging sources in the environment. From those, an optimal life history is determined, assuming that reproduction is an allometric function of size. 3. The optimal life history involves a behavioural trait (intensity of foraging) and an allocation process (amount of energy allocated to repair of damage). Subsequent to the imprinting period, the organism lives experiencing levels of stress or caloric intake that differ from those during the imprinting period. The mismatch is such that either the caloric intake is greater postimprinting than during imprinting or environmental stress is smaller post-imprinting that during imprinting. 4. Since reproduction is given allometrically and the organism cannot shrink, there is no reproductive senescence. In all cases, mortality increases with age. Senescence is caused by accumulated damage and we focus on the allocation of potential growth to repair and environmental mismatch. 5. In the case of stress mismatch, the general qualitative result is that both the optimal level of activity and the allocation to repair are greater than their values in the case of no mismatch and they are positively correlated. For caloric mismatch, during the post-imprinting period the intensity of foraging is greater than that predicted if there were no mismatches. However, we predict either a negative correlation between genes characterizing activity and repair (for small mismatch), no correlation (for moderate mismatch) or positive correlation (for large mismatch). Furthermore, caloric mismatch is predicted to lead to a considerable reduction in lifetime reproduction, but stress mismatch is predicted to induce an increase in stress resistance throughout life with little cost to lifetime reproduction.

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Section: Introductionmentioning

confidence: 99%

Environment, damage and senescence: modelling the life‐history consequences of variable stress and caloric intake

Mangel¹

2008

Functional Ecology

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“…It should be pointed out that cultivation of cells in 40% oxygen (mild oxidative stress) makes them more resistant to oxidative damage that occurs during starvation. Cells with low lipofuscin content (used as controls) were not exposed to 40% oxygen and, therefore, a higher resistance of lipofuscin-rich cells to starvation could rather depend on preconditioning to oxidative stress than on lipofuscin per se [93]. Our earlier observations, in which fibroblasts from same culture dishes but with different lipofuscin content were compared, demonstrated decreased resistance of lipofuscin-rich cells to amino acid starvation [21] or acute oxidative stress [94].…”

Section: Imperfect Lysosome Function In Aging and Heart Diseasementioning

confidence: 99%

The Involvement of Lysosomes in Myocardial Aging and Disease

Terman

Kurz²,

Gustafsson³

et al. 2008

CCR

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The myocardium is mainly composed of long-lived postmitotic cells with, if there is any at all, a very low rate of replacement through the division and differentiation of stem cells. As a consequence, cardiac myocytes gradually undergo pronounced age-related alterations which, furthermore, occur at a rate that inversely correlates with the longevity of species. Basically, these alterations represent the accumulation of structures that have been damaged by oxidation and that are useless and often harmful. These structures (so-called ‘waste’ materials), include defective mitochondria, aberrant cytosolic proteins, often in aggregated form, and lipofuscin, which is an intralysosomal undegradable polymeric substance. The accumulation of ‘waste’ reflects the insufficient capacity for autophagy of the lysosomal compartment, as well as the less than perfect functioning of proteasomes, calpains and other cellular digestive systems. Senescent mitochondria are usually enlarged, show reduced potential over their inner membrane, are deficient in ATP production, and often produce increased amounts of reactive oxygen species. The turnover of damaged cellular structures is hindered by an increased lipofuscin loading of the lysosomal compartment. This particularly restricts the autophagic turnover of enlarged, defective mitochondria, by diverting the flow of lysosomal hydrolases from autophagic vacuoles to lipofuscin-loaded lysosomes where the enzymes are lost, since lipofuscin is not degradable by lysosomal hydrolases. As a consequence, aged lipofuscin-rich cardiac myocytes become overloaded with damaged mitochondria, leading to increased oxidative stress, apoptotic cell death, and the gradual development of heart failure. Defective lysosomal function also underlies myocardial degeneration in various lysosomal storage diseases, while other forms of cardiomyopathies develop due to mitochondrial DNA mutations, resulting in an accumulation of abnormal mitochondria that are not properly eliminated by autophagy. The degradation of iron-saturated ferritin in lysosomes mediates myocardial injury in hemochromatosis, an acquired or hereditary disease associated with iron overload. Lysosomes then become sensitized to oxidative stress by the overload of low mass, redox-active iron that accumulates when iron-saturated ferritin is degraded following autophagy. Lysosomal destabilization is of importance in the induction and/or execution of programmed cell death (either classical apoptotic or autophagic), which is a common manifestation of myocardial aging and a variety of cardiac pathologies.

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“…2,3 Exposure to mild and temporary oxidative stress (preconditioning) often protects against a later more pronounced exposure to such stress, which might otherwise have been lethal. [4][5][6][7] A major reason why oxidative stress is cytotoxic is that it causes lysosomal destabilization with ensuing relocation to the cytosol of a multitude of lytic enzymes. [8][9][10][11] Lysosomes are sensitive to oxidative stress because they contain a considerable amount of redox-active iron, which is released from ferruginous (iron-containing) materials, such as ferritin and mitochondrial complexes, while they are undergoing autophagic degradation.…”

mentioning

confidence: 99%