Is IRON the next anti aging target?

https://www.nature.com/articles/s41467-020-17312-3

Several of the genes we identify have previously been shown to influence lifespan in experiments on model organisms. For example, knockouts of the orthologs of APOE, LDLR, CDKN2B, and RBM38 in mice shortens their lifespan24,25,26,27, while knockout of IGF1R has the opposite effect28. Similarly, overexpression of the FOXO3 orthologue in Drosophila melanogaster29 and the SNCA orthologue in Caenorhabditis elegans30 have shown to extend their respective lifespans. Many of our genes are also enriched for pathways previously related to ageing in eukaryotic model organisms, including genomic stability, cellular senescence, and nutrient sensing31. For example, FOXO3 and IGF1R are well-known players modulating survival in response to dietary restriction32, but we also highlight genes involved in the response to DNA damage and apoptosis, such as CDKN2B, USP28, E2F2, and BCL3. In addition to hallmarks discovered in model organisms, our results suggest that haem metabolism may play a role in human ageing. This pathway includes genes involved in processing haem and differentiation of erythroblasts33. Although the enrichment is largely driven by genes linked to the LDLR locus, genes linked to other loci of interest (such as FOXO3, CDKN2B, LINC02513) are involved in similar biological pathways: myeloid differentiation, erythrocyte homeostasis, and chemical homeostasis.

The pathway analysis has potential limitations due to the correlative nature of the genes used to test for enrichment, which can inflate type 1 errors34. However, the strong signal for haem metabolism, in combination with the MR results, suggests the evidence for the involvement of this pathway in human ageing is reasonably robust. Haem synthesis declines with age and its deficiency leads to iron accumulation, oxidative stress, and mitochondrial dysfunction35. In turn, iron accumulation helps pathogens to sustain an infection36, which is in line with the known increase in infection susceptibility with age37. In the brain, abnormal iron homeostasis is commonly seen in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease and multiple sclerosis38. Plasma ferritin concentration, a proxy for iron accumulation when unadjusted for plasma iron levels, has been associated with premature mortality in observational studies39, and has been linked to liver disease, osteoarthritis, and systemic inflammation in MR studies40,41.

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    • BobM
    • BobM
    • 3 yrs ago
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    Hi Andrew, I have pondered irons role in artery diseases, plaque accumulation, etc. I have seen high iron in my blood readings from time to time. I wonder what role it plays. 

    I concluded as we get past 60 (?) we need to give Blood regularly. Especially men. It might help several things.
    I’m going to add this to my regimen. 

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    • Randy B
    • Randall_Bagrowski
    • 3 yrs ago
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    Iron accumulation has been associated with poor health for a very long time.  Women's risk for heart disease increases to that of men's after they reach menopause because they no longer have the ability to get rid of iron on a monthly basis. Blood donation is your best bet to lower iron levels.

    Like 1
  • This new study found genes associated with aging, knowledge that was previously unknown.

    Any new knowledge is exciting.

    What to do with this new knowledge?

    Wait for studies to tell us what to do? That might take decades.

    Donate blood? How often? How soon after donating blood will iron rebound in the body? Is donating blood harmful, especially for older folks?

    Iron chelators?  What dosage? For how long? Will it lead to iron deficiencies? Will iron levels rebound after stopping?

    Switch to a low iron diet, like cutting down on the consumption of red meats? Is that enough?

    Switch to a diet rich in natural iron chelators?

    There's just too much we still don't know.

    What I'm going to do, personally is to take low dosage iron chelators and observe how I feel. You know, experiment with my own body.

    They're lots of good studies on iron chelators out there.

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  • Apparently fisetin, quercetin and apigenin are iron chelators! The senolytics we are already talking.

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    • Larry
    • Larry.1
    • 3 yrs ago
    • Reported - view

    Curcumin and a number of other phytochemicals are possible Iron chelators. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821171/

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    • Larry
    • Larry.1
    • 3 yrs ago
    • Reported - view

    Donating blood is probably the best way to reduce Iron. 

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  • The page referenced this study which had some interesting data. https://pubmed.ncbi.nlm.nih.gov/25156997/

    average lifespan for various ferritin levels

    20-200 = 79 years old

    200-399 = 76 years old

    400-599 = 72 years old

    600+     = 55 years old

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    • MAC
    • MAC
    • 3 yrs ago
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    I donate about 500mL every 8 weeks (Canada). My Ferritin last labs was 15, saturation 20%. Iron dumping is just one of the my longevity hacks, for many of the reasons already posted above. I eat animal protein, nuts, bakers chocolate, spinach, all super nutrient foods for longevity, and there's no risk of iron depletion.

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    • MAC Thats great, donating blood is a great longevity hack, I have been doing it for four years. However Ferritin  15 and iron saturation 20% is too low and is going to make you fatigued. Iron institute says to shoot for 50 ferritin so you dont get anemic. I speak from experience, 25% sat or below makes me fatigued and below 50 ferritin can also do it. I would skip a few months and let your numbers build and you will see that you feel better.

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    • MAC
    • MAC
    • 3 yrs ago
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    My ferritin bounces around from between 15-35 depending on what I’ve eaten in the interim. Ferritin is also not that accurate the cellular iron stores; total iron binding capacity and saturation is more important. I do daily intense exercise, combined cardio and resistance session lasting typically 60-90 minutes, and if I felt tired in any way, I would most certainly dial back. I workout even on days I give blood in the AM. So I stress test myself! I am using biomarkers and how I feel dictate. Living on the “bleeding edge” :-) 

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