Iron accumulation during development and ageing of Drosophila

Massie, Harold R.; Aiello, Valerie R.; Williams, T. R.

doi:10.1016/0047-6374(85)90020-x

Cited by 54 publications

(37 citation statements)

References 13 publications

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“…Thus, iron accumulation may simply be a negative consequence of increased oxidant production during senescence that contributes to the overall level of oxidative stress within the cell. Support for this idea comes from work in other systems where iron accumulation was associated with decreased life span and iron chelation provides life-span extension (30,31,41). On the other hand, intracellular iron accumulation might have positive aspects in vivo.…”

Section: Discussionmentioning

confidence: 87%

Iron Accumulation During Cellular Senescence in Human FibroblastsIn Vitro

Killilea¹,

Atamna²,

Liao

et al. 2003

Antioxidants & Redox Signaling

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Iron accumulates as a function of age in several tissues in vivo and is associated with the pathology of numerous age-related diseases. The molecular basis of this change may be due to a loss of iron homeostasis at the cellular level. Therefore, changes in iron content in primary human fibroblast cells (IMR-90) were studied in vitro as a model of cellular senescence. Total iron content increased exponentially during cellular senescence, resulting in 10-fold higher levels of iron compared with young cells. Low-dose hydrogen peroxide (H 2 O 2 ) induced early senescence in IMR-90s and concomitantly accelerated iron accumulation. Furthermore, senescence-related and H 2 O 2 -stimulated iron accumulation was attenuated by N-tert-butylhydroxylamine (NtBHA), a mitochondrial antioxidant that delays senescence in vitro. However, SV40-transformed, immortalized IMR-90s showed no time-dependent changes in metal content in culture or when treated with H 2 O 2 and/or NtBHA. These data indicate that iron accumulation occurs during normal cellular senescence in vitro. This accumulation of iron may contribute to the increased oxidative stress and cellular dysfunction seen in senescent cells.

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Section: Discussionmentioning

confidence: 87%

Iron Accumulation During Cellular Senescence in Human FibroblastsIn Vitro

Killilea¹,

Atamna²,

Liao

et al. 2003

Antioxidants & Redox Signaling

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“…We reasoned that, unless potent compensatory mechanisms were in place, we would be able to identify deficiencies for those metals that depend primarily on the Mvl protein (Drosophila DMT1) for cellular import. We used adult populations of mixed sex and only collected flies 4-7days post-eclosion, because, at least in the cases of copper and iron, ageing flies accumulate metals (Massie et al, 1980;Massie et al, 1985). Cohorts of flies were raised to adults on diets including 1mmoll -1 concentrations of each metal, which they tolerated well (see Materials and methods).…”

Section: Resultsmentioning

confidence: 99%

Iron depletion in the intestines ofMalvoliomutant flies does not occur in the absence of a multicopper oxidase

Bettedi

Aslam

Szular

et al. 2011

Journal of Experimental Biology

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SUMMARYMalvolio (Mvl) encodes the sole Drosophila melanogaster homologue of divalent metal transporter-1 (DMT1). The Drosophila transporter has been implicated in iron, manganese and copper cellular import. Indeed, the extent of metal specificity for this family of transporters is still under investigation in many eukaryotic species. Here, we revisit metal accumulation in Mvl mutants raised under normal and metal-supplemented diets. We found iron deficiency in Mvl mutant flies, whereas whole body copper and manganese concentrations remained unaltered. Iron supplementation restored total body iron concentrations in Mvl mutants, but without replenishing iron stores in the middle midgut, suggesting a role for Mvl in systemic iron trafficking, in addition to a role in intestinal iron absorption. Interestingly, dietary copper sulphate supplementation further exacerbated the iron deficiency. We investigated whether dietary copper affected iron storage through the function of an insect multicopper oxidase (MCO), because the mammalian MCO ceruloplasmin is known to regulate iron storage in the liver. We identified a Drosophila MCO mutant that suppressed aspects of the Mvl mutant phenotype and most notably Mvl, MCO3 double mutants showed normal intestinal iron storage. Therefore, MCO3 may encode an insect ferroxidase. Intriguingly, MCO3 mutants had a mild accumulation of copper, which was suppressed in Mvl mutants, revealing a reciprocal genetic interaction between the two genes. Supplementary material available online at

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“…The mechanism of iron toxicity is likely related to promotion of damaging free-radical reactions and associated inflammation (Smith et al, 1997) (reviewed in Kell, 2009). It is thus not surprising that invertebrate data (Drosophila) suggest that age-related iron accumulation is proportional to the rate of aging (Massie et al, 1985) and inhibition of iron absorption prolongs lifespan (Massie et al, 1993). Similarly, human gender differences in longevity have been proposed to relate to reproduction-related iron losses in women (Sullivan, 1989) and life-extending effects of calorie restriction have been associated with reduced dietary iron uptake and lowered iron deposits in tissue (Cook and Yu, 1998;Kastman et al, 2010;Valle et al, 2008;Xu et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Gender and Iron Genes May Modify Associations Between Brain Iron and Memory in Healthy Aging

Bartzokis

Tingus

et al. 2011

Neuropsychopharmacol

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Brain iron increases with age and is abnormally elevated early in the disease process in several neurodegenerative disorders that impact memory including Alzheimer's disease (AD). Higher brain iron levels are associated with male gender and presence of highly prevalent allelic variants in genes encoding for iron metabolism proteins (hemochromatosis H63D (HFE H63D) and transferrin C2 (TfC2)). In this study, we examined whether in healthy older individuals memory performance is associated with increased brain iron, and whether gender and gene variant carrier (IRON + ) vs noncarrier (IRONÀ) status (for HFE H63D/TfC2) modify the associations. Tissue iron deposited in ferritin molecules can be measured in vivo with magnetic resonance imaging utilizing the field-dependent relaxation rate increase (FDRI) method. FDRI was assessed in hippocampus, basal ganglia, and white matter, and IRON + vs IRONÀ status was determined in a cohort of 63 healthy older individuals. Three cognitive domains were assessed: verbal memory (delayed recall), working memory/attention, and processing speed. Independent of gene status, worse verbal-memory performance was associated with higher hippocampal iron in men (r ¼ À0.50, p ¼ 0.003) but not in women. Independent of gender, worse verbal working memory performance was associated with higher basal ganglia iron in IRONÀ group (r ¼ À0.49, p ¼ 0.005) but not in the IRON + group. Between-group interactions (p ¼ 0.006) were noted for both of these associations. No significant associations with white matter or processing speed were observed. The results suggest that in specific subgroups of healthy older individuals, higher accumulations of iron in vulnerable gray matter regions may adversely impact memory functions and could represent a risk factor for accelerated cognitive decline. Combining genetic and MRI biomarkers may provide opportunities to design primary prevention clinical trials that target high-risk groups.

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Iron accumulation during development and ageing of Drosophila

Cited by 54 publications

References 13 publications

Iron Accumulation During Cellular Senescence in Human FibroblastsIn Vitro

Iron Accumulation During Cellular Senescence in Human FibroblastsIn Vitro

Iron depletion in the intestines ofMalvoliomutant flies does not occur in the absence of a multicopper oxidase

Gender and Iron Genes May Modify Associations Between Brain Iron and Memory in Healthy Aging

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