Age-related Iron Accumulation

This article is evidence of the Herbivore
Hypothesis of accumulation of iron over
time in the human body leads to disease in
old age.

Iron Accumulation with Age, Oxidative Stress
and Functional Decline
Jinze Xu,1 Mitchell D. Knutson,2* Christy S. Carter,
1,3 and Christiaan Leeuwenburgh1*
1Department of Aging and Geriatrics,
Division of Biology of Aging,
Genomics and Biomarkers Core of The Institute on Aging,
University of Florida, Gainesville, Florida,
United States of America
2Food Science and Human Nutrition Department,
University of Florida, Gainesville, Florida,
United States of America
3Gainesville VA Geriatric Research,
Education and Clinical Center (GRECC),
Gainesville, Florida, United States of America
Marcelo Hermes-Lima, Editor
Universidade de Brasília, Brazil

E-mail: (CL); Email: (MK)
Conceived and designed the experiments: JX MDK CL.
Performed the experiments: JX CSC.
Analyzed the data: JX MDK CSC CL.
Contributed reagents/materials/analysis tools: JX CSC CL.
Wrote the paper: JX MDK CSC CL.
Received April 25, 2008; Accepted July 10, 2008.

Identification of biological mediators in sarcopenia is pertinent to the
development of targeted interventions to alleviate this condition.
Iron is recognized as a potent pro-oxidant and a catalyst for the
formation of reactive oxygen species in biological systems.
It is well accepted that iron accumulates with senescence in several
organs, but little is known about iron accumulation in muscle and
how it may affect muscle function.
In addition, it is unclear if interventions which reduced age-related loss
of muscle quality, such as calorie restriction, impact iron accumulation.
We investigated non-heme iron concentration, oxidative stress to nucleic
acids in gastrocnemius muscle and key indices of sarcopenia (muscle
mass and grip strength) in male Fischer 344 X Brown Norway rats fed
ad libitum (AL) or a calorie restricted diet (60% of ad libitum food intake
starting at 4 months of age) at 8, 18, 29 and 37 months of age.
Total non-heme iron levels in the gastrocnemius muscle of AL rats
increased progressively with age.
Between 29 and 37 months of age, the non-heme iron concentration
increased by approximately 200% in AL-fed rats.
Most importantly, the levels of oxidized RNA in gastrocnemius muscle
of AL rats were significantly increased as well.
The striking age-associated increase in non-heme iron and oxidized
RNA levels and decrease in sarcopenia indices were all attenuated in
the calorie restriction (CR) rats.
These findings strongly suggest that the age-related iron accumulation
in muscle contributes to increased oxidative damage and sarcopenia,
and that CR effectively attenuates these negative effects.
PLoS ONE. 2008; 3(8): e2865.
Published online 2008 August 6.
doi: 10.1371/journal.pone.0002865.
PMCID: PMC2481398
Copyright Xu et al.
This is an open-access article distributed under the terms of the
Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original
author and source are credited.

Copyright © 2009 by The American Association of Immunologists, Inc.
All rights reserved.
The Herbivore Hypothesis hinges on the fact the iron from the meat one eats
progressively accumulates in the human body and causes disease.

“It is well accepted that iron accumulates with senescence in several organs,
but little is known about iron accumulation in muscle.

These findings strongly suggest that the age-related accumulation in muscle iron
contributes to increased oxidative stress and sarcopenia, and that caloric restriction
effectively attenuates these negative effects.”

The latest studies have now recommended bloodletting / iron reduction for hepatitis and alzheimers’.

An article speaking to bloodletting for hepatitis can be found here.

Phlebotomy Gaining Acceptance as HCV Treatment

“Learn how the safe ancient practice of bloodletting, or phlebotomy,
has proven therapeutic value, and why it is gaining momentum as a
treatment of chronic Hepatitis C.”

The latest article among many speaking to iron reduction for Alzheimer’s
can be found here.

Getting the iron out: Phlebotomy for Alzheimer’s disease?

“This communication explores the temporal link between the age-associated
increase in body iron stores and the age-related incidence of Alzheimer’s
disease (AD), the most prevalent cause of senile dementia.
Body iron stores that increase with age could be pivotal to AD pathogenesis
and progression.”


700% Decrease In Liver Cancer
Lactoferrin is an iron binding protein produced in our bodies to capture iron
and remove it away from an invader.
A form of lactoferrin has been isolated from cow’s milk and has shown some
promising possibilities.
Targeting iron in liver cancer leads to a 700% increased .. survival ..

That’s a good thing ..

“Survival rates were 12.5% vs. 91.7%”

Bovine lactoferrin potently inhibits liver mitochondrial 8-OHdG levels
and retrieves hepatic OGG1 activities in Long-Evans Cinnamon rats.
J Hepatol. 2008 Mar;48(3):486-93. Epub 2007 Dec 27.
Tsubota A, Yoshikawa T, Nariai K, Mitsunaga M, Yumoto Y, Fukushima K,
Hoshina S, Fujise K.

Institute of Clinical Medicine and Research (ICMR), Jikei University
School of Medicine, Kashiwa, Chiba, Japan. ats…

To assess the effect of lactoferrin on oxidative liver damage and its
mechanism, we used Long-Evans Cinnamon (LEC) rats that
spontaneously develop fulminant-like hepatitis and lethal hepatic f
Four-week-old female LEC rats were divided into the untreated and
treated groups. The latter was fed bovine lactoferrin at 2% mixed
with conventional diet.
The cumulative survival rates were 75.0% vs. 100% at 14 weeks, 37.5%
vs. 91.7% at 15 weeks, and 12.5% vs. 91.7% at 16 weeks, respectively,
for untreated and treated rats (P=0.0008).
The 8-OHdG levels in liver mitochondrial DNA and malondialdehyde in
plasma and liver tissues were significantly lower in treated than untreated
rats (P<0.001, =0.017 and 0.034, respectively).
Mitochondrial DNA mutations were more common in untreated rats.
OGG1 mRNA and protein expression levels were significantly lower in
untreated than treated rats (P=0.003 and 0.007, respectively).
Hypermethylation of the second CpG island located upstream of OGG1
gene was observed in untreated rats.
survival rates were 12.5% vs. 91.7%
Our findings indicated that lactoferrin inhibits oxidative liver damage in LEC
Lactoferrin could be potentially useful for the treatment of oxidative
stress-induced liver diseases.

Publication Types:
Research Support, Non-U.S. Gov’t

PMID: 18191270


Antibiotic Properties and Applications of Lactoferrin.
Curr Pharm Des 2007; 13(8):801-802.
Weinberg ED

Lactoferrin (Lf), a mammalian iron scavenging defense protein,
constitutively is present in exocrine secretions that consistently
are exposed to microbial flora: milk, tears, tubotympanum and nasal
exudate, saliva, bronchial mucus, gastrointestinal fluids,
cervicovaginal mucus, and seminal fluid.
Additionally, Lf is promptly delivered by circulating neutrophils to
sites of microbial invasion.
At these sites, the protein effectively scavenges iron at pH values
as low as 3.5.
Recombinant bovine and human lactoferrin is now available for
development into nutraceutical / preservative/pharmaceutical products.
Among conditions for which the products are being investigated are:
angiogenesis; bone remodeling; food preservation; infection in
animals, humans, plants; neoplasia in animals, humans; inflammation
in intestine, joints; wound healing; as well as enhancement of
antimicrobial and antineoplastic drugs, and prevention of iron
induced oxidation of milk formula.

Curr Pharm Des

Iron and infection: competition between host and microbes
for a precious element.
Marx JJ
Eijkman-Winkler Institute for Microbiology,
Infectious Diseases and Inflammation,
University Medical Centre Utrecht,
PO Box 85500, 3508 GA
Utrecht, The Netherlands.

During infection microbes attack host tissues, causing damage to specific
organs, sepsis or even death.
For proliferation microbes desperately need iron for which they have to compete
with the host.
Micro-organisms have developed an abundant number of strategies to acquire iron
from their specific environment and to transport the element to sites of
incorporation into biologically important molecules.
As part of the non-specific defence mechanisms against infection, the body
modifies iron metabolism in order to make iron less available for
Such processes have a profound effect on the immune system and are also
expressed in other forms of inflammation.
Microbial iron transport systems are explored as targets for antibiotic
treatment and vaccines.
In particular, iron chelators, used for the treatment of iron overload may
become important drugs for fighting bacterial and viral infections.

PMID: 12401315, UI: 22288772