Dissociation between iron accumulation and ferritin upregulation in the aged substantia nigra: attenuation by dietary restriction.
Walker T1, Michaelides C1, Ekonomou A1, Geraki K2, Parkes HG3, Suessmilch M1, Herlihy AH4, Crum WR1, So PW1.
Aging (Albany NY). 2016 Oct 12. doi: 10.18632/aging.101069.
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.

KEYWORDS:
MRI; aging; basal ganglia; brain; dietary restriction; homeostatis; iron
PMID: 27743512 DOI: 10.18632/aging.101069

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