Young Blood, Aging, and Iron


The by-now famous experiments that have tied the circulations of young and old animals together, showing the rejuvenating effects of “young blood”, have also shown that the harmful effects of old blood may be greater than the rejuvenating effects of young blood. There’s something about old blood — likely many things — that cause a young animal to show signs of aging; I’ve speculated that two of the more important factors might be iron and bacterial lipopolysaccharides — or possibly the bacteria themselves. Here we’ll discuss the links among young blood, aging, and iron.

Of course, other elements in old blood differ in quantity from those in young blood, and scientists are studying a number of candidates that take the form the form of proteins, as Josh Mitteldorf discusses in his latest article.  (See my review of Josh’s book, Cracking the Aging Code.) One of the proteins under investigation is VCAM-1, for vascular cell adhesion molecule, the level of which increases in old blood.

Exposure of young animals to old blood increases the expression of VCAM-1.

Studies from our lab and others have recently shown that brain function – specifically neurogenesis, synaptic plasticity and cognitive function in the hippocampus, a key center for learning and memory– is inhibited in young mice connected to aged mice through heterochronic parabiosis or aged plasma intravenous injections….  BECs [brain endothelial cells] upregulate expression of vascular adhesion molecules as a result of increased systemic inflammatory signaling resulting from multiple diseases that afflict the CNS. We discovered that BEC-specific VCAM1 increases in the hippocampus during normal aging. Exposure of young BECs to an aged systemic environment induces BEC activation and upregulation of VCAM1 both in vitro and in vivo. Specifically, systemic injections of aged human blood into young immunodeficient (NSG) mice- acutely over 4 days or spread over 3 weeks- increased BEC-specific VCAM1 expression, increased brain inflammation as assessed by microglial activation, and inhibited hippocampal neurogenesis. Blocking VCAM1 signaling systemically with a neutralizing monoclonal antibody rescued neurogenesis and prevented aged plasma induced microglial activation. This study suggests preventing BEC-immune cell crosstalk through VCAM1 may be a therapeutic target for ameliorating aged blood induced decline in brain function. 

To decipher: old blood injected into young mice → brain inflammation and ↑VCAM-1 production. Blocking VCAM-1 with an antibody abolished this effect, showing that VCAM-1 is the culprit, or one of them, in brain inflammation.

But, what is it about old blood that causes an increase in VCAM-1 expression?

It may very well be iron. The addition of iron chelators to endothelial cell cultures reduces, in a dose- and time-dependent manner, the production of VCAM-1.

These data suggest that iron plays a critical role in TNFα mediated VCAM-1 induction in HDMEC [human dermal microvascular endothelial cells], and the target for iron effects may be IRF-1, NF-kB, and potentially chromatin remodeling.

Iron could be one of the main factors in old blood that causes inflammation and damage.

NF-kappa B is another molecule that’s been suggested as a pro-aging factor in old blood; it’s a master regulator of factors that increase inflammation, which is a key characteristic of aging.

Iron chelators block the increase in NF-kappa B.

These results demonstrate that the iron chelator effectively blocks NF-kappa B activation and coordinate TNF-alpha and IL-6 gene upregulation by HM [hepatic macrophages] in cholestatic liver injury or under in vitro lipopolysaccharide stimulation. These findings support a pivotal role for iron in activation of NF-kappa B and cytokine gene expression by HM in vitro and in vivo.

Iron satisfies a few other requirements for evidence of being involved in aging:

  1. Iron increases in aging.
  2. Iron promotes oxidative stress, a key characteristic of aging.
  3. Iron is implicated in diseases of aging, including heart disease, cancer, and Alzheimer’s.
  4. Iron promotes infections, which increase in aging.
  5. Iron promotes mTOR activation, thought to be critical in aging.

Here we have an element, iron, which looks to me like a prime candidate in aging promotion. Why aging researchers generally don’t see this, I don’t know, but possibly iron just isn’t a sexy topic. Or, I could be wrong, but obviously I doubt it.

I’ll just leave you with one other item of interest.

Restored Vulnerability of Cultured Endothelial Cells to High Glucose by Iron Replenishment. When endothelial cells are serially cultured, they lose their sensitivity to damage by high glucose, which is normally toxic. It turns out that serial culturing causes them to lose their iron, to a level only 10% that of normal. When the cells were incubated with iron, they took it up, their iron levels were restored to normal, and high glucose once again became toxic to them.


PS: Check out my books, Dumping Iron, Muscle Up, and Stop the Clock.

PPS: You can support this site by purchasing through my Supplements Buying Guide for Men.


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Young Blood, Aging, and Iron says January 23, 2017

[…] post Young Blood, Aging, and Iron appeared first on Rogue Health and […]

Rob H says January 29, 2017

Hi Dennis,

I think you may be interested to hear this one: Chris Masterjohn has a new podcast talking about iron: it is a very interesting listen as this guy is a very highly respected researcher with many years working in the field of nutrition: He takes the science very seriously as you will hear! The only thing I would warn you is that his audience is probably more broadly split across males and females than the mighty Rogue Health, so he does talk at some length about how to avoid anaemia – however he goes on to say that HIS particular issue is in fact iron overload. Some great take-outs for me, which echo yours are:
– Take some cheese when eating heme iron (since ONLY calcium can block the absorption of heme iron).
– Polyphenols & phytates block the absorption of non-heme, ie plant iron ONLY.
– Avoid taking vitamin C with plant iron as it boosts the bio-availability of the plant iron.
– Nrf2 inducers (eg Resveratrol, green tea extract, sulforaphane, Milk Thistle, Protandim) will all reduce free iron: because they induce hormesis, which in turn upregulates ferritin which then sequesters away more free iron (this is nothing to do with the relative absorption points of heme vs non-heme iron made above though).
– As per your comment to me in the ‘my supplements stack’ I will spread out my polyphenol supplements through the day, as opposed to taking them all at once (due to the overlapping mechanism of action): eg green tea extract in the morning, grapeseed extract (every other day) with lunch and resveratrol in the evening – so that they can address any iron consumed at each of my 3 x meals per day.

PS I know it would be easier to just donate blood but I have a stupid needle-phobia which seems to have no basis in logic.. Very weird.

Anti-Aging Drugs Rapamycin and Metformin Decrease Iron - Rogue Health and Fitness says April 23, 2017

[…] Iron promotes aging. I’m going to be going to my grave (ha ha) saying this. […]

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