Faculty Opinions recommendation of Cysteine Toxicity Drives Age-Related Mitochondrial Decline by Altering Iron Homeostasis.

Oxidative stress is a major factor in the pathogenesis of age-related macular degeneration (AMD). Iron may catalyze the Fenton reaction resulting in overproduction of reactive oxygen species. Transferrin receptor 2 plays a critical role in iron homeostasis and variability in its gene may influence oxidative stress and AMD occurrence. To verify this hypothesis we assessed the association between polymorphisms of theTFR2gene and AMD. A total of 493 AMD patients and 171 matched controls were genotyped for the two polymorphisms of theTFR2gene: c.1892C>T (rs2075674) and c.−258+123T>C (rs4434553). We also assessed the modulation of some AMD risk factors by these polymorphisms. The CC and TT genotypes of the c.1892C>T were associated with AMD occurrence but the latter only in obese patients. The other polymorphism was not associated with AMD occurrence, but the CC genotype was correlated with an increasing AMD frequency in subjects withBMI<26. The TT genotype and the T allele of this polymorphism decreased AMD occurrence in subjects above 72 years, whereas the TC genotype and the C allele increased occurrence of AMD in this group. The c.1892C>T and c.−258+123T>C polymorphisms of theTRF2gene may be associated with AMD occurrence, either directly or by modulation of risk factors.

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Age-Related Changes and Sex-Related Differences in Brain Iron Metabolism

Nutrients ◽

10.3390/nu12092601 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2601

Author(s):

Tanja Grubić Kezele ◽

Božena Ćurko-Cofek

Keyword(s):

Iron Metabolism ◽

Neurological Disorders ◽

Healthy Aging ◽

Iron Homeostasis ◽

Essential Element ◽

Molecular Alterations ◽

Age Related ◽

Faster Development ◽

Brain Iron Metabolism ◽

Age Related Changes

Iron is an essential element that participates in numerous cellular processes. Any disruption of iron homeostasis leads to either iron deficiency or iron overload, which can be detrimental for humans’ health, especially in elderly. Each of these changes contributes to the faster development of many neurological disorders or stimulates progression of already present diseases. Age-related cellular and molecular alterations in iron metabolism can also lead to iron dyshomeostasis and deposition. Iron deposits can contribute to the development of inflammation, abnormal protein aggregation, and degeneration in the central nervous system (CNS), leading to the progressive decline in cognitive processes, contributing to pathophysiology of stroke and dysfunctions of body metabolism. Besides, since iron plays an important role in both neuroprotection and neurodegeneration, dietary iron homeostasis should be considered with caution. Recently, there has been increased interest in sex-related differences in iron metabolism and iron homeostasis. These differences have not yet been fully elucidated. In this review we will discuss the latest discoveries in iron metabolism, age-related changes, along with the sex differences in iron content in serum and brain, within the healthy aging population and in neurological disorders such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and stroke.

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Age-related changes in iron homeostasis in mouse ferroxidase mutants

BioMetals ◽

10.1007/s10534-009-9229-0 ◽

2009 ◽

Vol 22 (5) ◽

pp. 827-834 ◽

Cited By ~ 10

Author(s):

Huijun Chen ◽

Zouhair K. Attieh ◽

Hua Gao ◽

Gang Huang ◽

Trent Su ◽

...

Keyword(s):

Iron Homeostasis ◽

Age Related ◽

Age Related Changes

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Linking Peroxiredoxin and Vacuolar-ATPase Functions in Calorie Restriction-Mediated Life Span Extension

International Journal of Cell Biology ◽

10.1155/2014/913071 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 15

Author(s):

Mikael Molin ◽

Ayse Banu Demir

Keyword(s):

Life Span ◽

Signaling Pathways ◽

Calorie Restriction ◽

Iron Homeostasis ◽

Vacuolar Atpase ◽

Beneficial Effects ◽

Age Related ◽

Nutrient Signaling ◽

Physiological Benefits ◽

Vacuolar Atpases

Calorie restriction (CR) is an intervention extending the life spans of many organisms. The mechanisms underlying CR-dependent retardation of aging are still poorly understood. Despite mechanisms involving conserved nutrient signaling pathways proposed, few target processes that can account for CR-mediated longevity have so far been identified. Recently, both peroxiredoxins and vacuolar-ATPases were reported to control CR-mediated retardation of aging downstream of conserved nutrient signaling pathways. In this review, we focus on peroxiredoxin-mediated stress-defence and vacuolar-ATPase regulated acidification and pinpoint common denominators between the two mechanisms proposed for how CR extends life span. Both the activities of peroxiredoxins and vacuolar-ATPases are stimulated upon CR through reduced activities in conserved nutrient signaling pathways and both seem to stimulate cellular resistance to peroxide-stress. However, whereas vacuolar-ATPases have recently been suggested to control both Ras-cAMP-PKA- and TORC1-mediated nutrient signaling, neither the physiological benefits of a proposed role for peroxiredoxins in H2O2-signaling nor downstream targets regulated are known. Both peroxiredoxins and vacuolar-ATPases do, however, impinge on mitochondrial iron-metabolism and further characterization of their impact on iron homeostasis and peroxide-resistance might therefore increase our understanding of the beneficial effects of CR on aging and age-related diseases.

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