During aging as well as during Alzheimer’s or Parkinson’s disease, iron accumulates in the human brain. Now, researchers found that in vertebrates, a microRNA called miR-29 inhibits these deposits – possibly offering new ways to treat Alzheimer’s and Parkinson’s disease as well as strokes. Results were published in the Journal BMC Biology on February 13, 2017.
Anti-Aging Molecule in the Brain
As we get older, our brain ages. Cognitive abilities decline and the risk of developing neurodegenerative diseases like dementia, Alzheimer’s and Parkinson’s disease or having a stroke steadily increases.
Aging in fast motion: The natural lifespan of N. furzeri is only few months (left: male of long-lived strain, aged 6 months; right: geriatric male aged 13 months). The African fish was used as aging model by researchers from Jena (Germany) and Pisa (Italy) to show that neurons are protected from iron-accumulation by an anti-aging microRNA. The results could offer a new approach for the treatment of neurodegenerative diseases.
A possible cause is the accumulation of iron molecules within neurons, which seems to be valid for all vertebrates. In a collaborative research project within the consortium JenAge, researchers from the Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) in Jena, Germany, and the Scuola Normale Superiore (SNS) in Pisa, Italy, found that this iron accumulation is linked to a microRNA called miR-29. This little molecule has so far been known to act as a tumor suppressor, hindering the proliferation of cancer cells.
However, clearly, miR-29 also regulates whether or not iron can be deposited in neurons. Using the African fish Nothobranchius furzeri – the shortest-living vertebrate that can be kept under laboratory conditions – the team of Alessandro Cellerino showed a large increase of iron deposits in fish where miR-29 had been suppressed, which led to premature brain aging. In contrast, healthy fish showed the more miR-29 in their neurons, the older they were. Hence, miR-29 acts as a kind of anti-aging molecule during aging, inhibiting the accumulation of iron in neurons.
Iron: Head Start on Treating Alzheimer’s?
„We strongly believe that our results are relevant for humans as well“, says Alessandro Cellerino, Professor of Physiology at SNS in Pisa and guest scientist at the FLI, who is one of the study’s leaders. In fact, the link between an increased iron accumulation and neurodegenerative diseases or strokes in humans has been known for some time; there are also results showing a reduced concentration of miR-29 in these diseases. However, it is totally new that miR-29 acts as molecular switch that inhibits iron accumulation. “These results are surprising – and very promising, because the development of miR-29-based pharmaceuticals for cancer therapy is already ongoing. This may offer a head start for the development of new therapies for Parkinson’s or Alzheimer’s disease and for the treatment of strokes as well”, Cellerino adds.
First Biomedical Discovery in New Fish Model Has Great Potential
African killifish Nothobranchius furzeri has only recently been introduced as animal model in aging research. It was the deciphering of the fish’s genome in late 2015 by the Leibniz Institute on Aging (FLI) that laid the foundation for genetic studies in this fast-aging vertebrate. “The investment of ten years, which it took us and our collaborators to decipher the genome, now starts to pay off”, explains Prof. K. Lenhard Rudolph, who is the FLI’s Scientific Director. And Mario Baumgart, a Postdoc at the FLI that was involved in the study, adds: “There’s no other vertebrate showing such a rapid aging as this little fish. It is like aging in fast motion. Moreover, 90% of human genes can be found in the fish as well, making almost all knowledge gained from N. furzeri transferable to humans.” This is why the results about the molecular switch miR-29, which were published on February 13, 2017 in the journal BMC Biology are so promising and mean a further step towards the treatment of neurodegenerative diseases.
Should I Worry?
Older people (male or female) are not prone to accumulating excess iron from a balanced healthy diet, moderate supplementation or alcohol consumption. This age group can potentially have toxic levels of iron in their organs and glands, if they abuse alcohol, consuming excessively of nicotine products (to stop smoking), on hormone replacement therapy, have B12 deficiencies, or are receiving repeated blood transfusion.
Although iron is an essential element for healthy life, too much iron can overwhelm the body’s natural storage capability leading to oxidative stress, tissue damage, and early aging. Iron is particularly dangerous and can catalyze these processes even in small amounts (less than a few extra grams) when mixed with other risk factors such as obesity, family history of diabetes or heart disease, inadequate consumption of antioxidants (fruits and vegetables), hormone replacement therapy, unhealthy cholesterol levels, smoking and regular alcohol consumption and for women who no longer menstruate.
Damage from Too Much Iron
Cell and tissue damage caused by iron can either initiate and/or contribute to the following causes of that can shorten lifespan or cause sudden death:
- Cirrhosis of the liver
- Cardiovascular diseases
- Cancer (particularly cancers of the liver and colon)
- Type II diabetes
- Septicemia (excessive iron nourishes dangerous microbe colonization)
- Early onset neurodegenerative diseases (Alzheimer’s and Parkinson’s diseases, among others)
Individual symptoms and degree of expression will vary between people (as will the amounts of stored iron). Excessive body iron accumulation can also lead to depression, loss of muscle mass and strength, enlargement and impairment of liver and spleen, loss of body hair, hypothyroidism, loss of libido (sexual interest) and function, with noticeable changes (darkening) of skin color, chronic fatigue and joint pain (especially in the first two knuckles of the hand referred to as “iron fist”.) Too much iron should be suspect in the presence of any of these symptoms. In women, the greatest risk for and indicator of suspect iron overload is when the monthly period stops for whatever reason: taking birth control pills, hysterectomy or menopause. With the monthly blood loss from a period iron is also lost, keeping excess iron under control.
Fortunately for most, iron metabolism is tightly regulated by their genes. Those lucky ones are similar to people who seem to be able to eat as much as they want and not get fat. Some people can consume plenty of iron-packed red meat and even imbibe in some potentially unhealthy habits, and yet not be further harmed by the invisible threat of adding too much iron to that potentially unhealthy mix. That’s because their metabolisms don’t permit absorption of any more iron than what’s needed for the body to function properly, which includes about one extra gram stored in reserve.
For older people with genetic hemochromatosis who also have a tendency or condition causing blood loss, the extra bit of stored iron may protect them from iron deficiency and anemia.
Diseases or conditions that can produce too much iron in the elderly include:
- Menopause (females)
- Genetic: hemochromatosis (HHC) or iron overload; for whites: type I (classic) hemochromatosis caused by mutations of HFE; four rarer non-HFE related disease include type 2 (A and B) hemochromatosis (juvenile hemochromatosis onset before age 30), type 3 hemochromatosis (transferrin receptor 2 hemochromatosis), type 4 (A and B) hemochromatosis (ferroportin disease), and a(hypo) ceruloplasminemia
- Genetic iron loading for non-whites: not fully known but suspect is for mutations of genes that regulate hepcidin, transferrin receptor 2 or the ferroportin gene; (Note: these mutations may also occur in white females as modifiers of HFE).
Genetic or acquired chronic hemolytic anemia (mechanical heart valve, blood cell disorders, enzyme deficiencies and rare cases autoimmune disease)
Acquired sideroblastic anemia
- Acquired iron overload from blood transfusion, excessive alcohol consumption, excessive use of iron supplements, hormone replacement or chronic use of nicotine products (to stop smoking)
- Detection (iron tests)
- Ripa R, Dolfi L, Terrigno M, Pandolfini L, Savino A, Arcucci V, Groth M, Terzibasi Tozzini E, Baumgart M, Cellerino A. MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging. BMC Biology 2017, 15:9, DOI: 10.1186/s12915-017-0354-x.