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Dissociation between iron accumulation and ferritin upregulation in the aged substantia nigra: attenuation by dietary restriction

DOI: 10.18632/aging.101069 DOI Help

Authors: Thomas Walker (Kings College London) , Christos Michaelides (King's College London) , Antigoni Ekonomou (King’s College London) , Tina Geraki (Diamond Light Source) , Harold G Parkes (Institute of Cancer Research) , Maria Suessmilch (King’s College London) , Amy H Herlihy (Perspectum Diagnostics) , William R Crum (King’s College London) , Po-wah So (King's College London)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Aging

State: Published (Approved)
Published: October 2016
Diamond Proposal Number(s): 9304

Abstract: Despite regulation, brain iron increases with aging and may enhance aging processes including neuroinflammation. Increases in magnetic resonance imaging transverse relaxation rates, R2 and R2*, in the brain have been observed during aging. We show R2 and R2* correlate well with iron content via direct correlation to semi-quantitative synchrotron-based X-ray fluorescence iron mapping, with age-associated R2 and R2* increases reflecting iron accumulation. Iron accumulation was concomitant with increased ferritin immunoreactivity in basal ganglia regions except in the substantia nigra (SN). The unexpected dissociation of iron accumulation from ferritin-upregulation in the SN suggests iron dyshomeostasis in the SN. Occurring alongside microgliosis and astrogliosis, iron dyshomeotasis may contribute to the particular vulnerability of the SN. Dietary restriction (DR) has long been touted to ameliorate brain aging and we show DR attenuated age-related in vivo R2 increases in the SN over ages 7 – 19 months, concomitant with normal iron-induction of ferritin expression and decreased microgliosis. Iron is known to induce microgliosis and conversely, microgliosis can induce iron accumulation, which of these may be the initial pathological aging event warrants further investigation. We suggest iron chelation therapies and anti-inflammatory treatments may be putative ‘anti-brain aging’ therapies and combining these strategies may be synergistic.

Journal Keywords: MRI, brain aging, iron homeostasis, dietary restriction, basal ganglia

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I18-Microfocus Spectroscopy