Can You Reverse Aging In humans with Certain Anti-inflammatory Supplements?
The quick answer to the question, Can you reverse aging in humans with supplements? is — probably not, but as you’ll soon see, there’s evidence that you might be able to slow down the aging process. And that’s good enough!
To be able to reverse aging in humans with supplements that reduce systemic inflammation seems like a pipe dream, but a just-released study in the journal Nature shows that a “tweak” to immune cells reversed aging in mice.
Yeah, I’m betting you’re not a mouse, but most of the genes in mice share functions with the genes in humans, and they’re unable to protest all the indignities pressed upon them by scientists who endeavor to make life better for humans, making them ideal lab rats, I mean lab mice.
And, I should add, that the “Nature” study did not reverse mouse aging by supplements; rather this was done by the inhibiting inflammatory PGE2 signaling through the myeloid EP2 receptor in the mice cohort.
Nonetheless, as I’ll show you, this may suggest that certain anti-inflammatory supplements can reverse aging in humans, at least a bit — or surely slow it down. I have some explaining to do, so let’s get at it by first positing that excess inflammation (i.e. systemic or chronic inflammation) is the focus here, as it’s a problem in aging.
It’s Called Inflammaging for A Reason
Excess inflammation contributes to chronic health issues issues like atherosclerosis, cancer, and cognitive decline. That’s clear, but what’s opaque is understanding the mechanisms behind age-related inflammation (inflammaging) are not well understood. But thanks to the Nature study, scientists were able to demonstrate that older immune cells have a defect in metabolism that when corrected in a mouse model of Alzheimer’s disease can decrease inflammation and restore cognitive function.
Why Alzheimer mice?
Mice with Alzheimer’s were used in the study because it’s known that systemically, circulating pro-inflammatory factors can promote cognitive decline. So, if the researchers could reverse the inflammatory-based pathology associated with Alzheimer’s, the mechanisms involved could have a physiologically systemic effect.
The connection between Alzheimer’s and inflammation
Epidemiological studies have long shown that people who occasionally took nonsteroidal anti-inflammatory drugs (such as ibuprofen and naproxen) for aches and pains had a decreased risk of Alzheimer’s disease. This was explained by studies indicating that overexpression of cyclooxygenase-2 (COX-2), a major mediator of inflammation in the brain led to Alzheimer’s disease-like symptoms in mice; namely, age-dependent inflammation and cognitive loss.
COX-2 activation is the first step in the production of a lipid called prostaglandin E2 (PGE2), which can bind to one of its receptors, EP2, on immune cells and promote inflammation.
OK, some definitions are in order:
- A lipid is a term for a fat or fat-like substance in the blood. The body stores fat as energy for future use, just like a car that has a reserve fuel tank. When the body needs energy, it can break down lipids into fatty acids and burn them like glucose.
- Prostaglandin E2 (PGE2) is a one of the prostaglandins, a group of hormone-like chemical messengers that participate in a wide range of body functions, such as the contraction and relaxation of smooth muscle, the dilation and constriction of blood vessels, control of blood pressure, and modulation of inflammation. PGE2 is a potent inflammatory mediator (induces inflammation) that is generated by cyclooxygenase 2 (COX2).
- Cyclooxygenase 2 (COX2) is an enzyme that acts to speed up the production of prostaglandins that play a key role in promoting inflammation. When cox-2 activity is blocked, inflammation is reduced.
- EP2 is a prostaglandin cell receptor for PGE2 and once activated can promote inflammation.
What all this boils down to is that:
Deleting the EP2 receptor in mouse macrophages (immune cells that gobble up pathogens) and brain-specific microglia (a type of macrophage) reduces inflammation and increases neuronal survival in response to both a bacterial toxin and a neurotoxin — and that means better cognitive function, plus you’ll soon see, more energy.
What does this mean for humans?
In the Nature study, the researchers wanted to understand how eliminating PGE2 signaling in macrophages could reduce inflammation, and if this happened in humans. To do this, they compared macrophages from human blood donors either younger than 35 or older than 65.
The cells from older donors made much more PGE2 and had higher abundance of the EP2 receptor than did macrophages from younger donors — that means the older donors were creating more inflammation. When the researchers exposed human macrophages to PGE2, the cells altered their metabolism. Rather than using glucose to make energy, the cells converted it to glycogen and stored it, locking it up where the mitochondria couldn’t access it for ATP production.
This is a key part of the study — that cells basically become energy-depleted as we age because their immune components (macrophages) stop clearing “debris”, such as the misfolded proteins associated with neurodegeneration.
To test this, the researchers treated human macrophages from donors with an average age of about 48 with one of two EP2 receptor inhibitors, resulting in:
- A decrease of glycogen storage,
- An increase of energy production, and
- Cells shifted to express anti-inflammatory markers.
Using this same process with mice yielded the same results: metabolism improved, and age-associated cognitive decline reversed.
Can Supplements Reverse Aging In Humans?
As mentioned at the start of this post, the Nature experiment did not use supplements to reverse cognitive decline and increase metabolism/energy; rather mice genes were manipulated. That’s not going to happen to you; not yet. This begs the question:
Can anything be done to suppress prostaglandins?
Remember, prostaglandins, namely PGE2 promotes inflammation, and we know that certain drugs like ibuprofen and naproxen can reduce inflammation. But what about supplements? Well, there are two studies I’d like to bring to your attention.
A study published in the journal Molecules in 2020 examined natural-derived compounds that target immune cells and prostaglandins as alternate therapies for autoimmune and inflammatory-based diseases.
The study’s authors came up with a lengthy list of supplements, mainly botanicals, that they deem are effective anti-inflammatory agents, of which I’ll list three that got the most attention:
- Epi-gallocatechin gallate (EGCG) — think green tea –may effectively improve the symptoms and inflammatory conditions of autoimmune diseases, and is viewed as an anti-inflammatory agent.
- Baicalin, from Scutellaria baicalensis, or “Chinese Skullcap”, has been shown to effectively reduce inflammation and tissue damage in colitis, and modulate inflammatory imbalance in the colon, ameliorating colorectal inflammation.
- Glycyrrhizin (or glycyrrhizic acid, “Licorice Root”) has been shown to possess several beneficial pharmacological activities, including anti-asthmatic effects and anti-inflammatory activity that balances and regulates the immune response in different models of chronic inflammation.
I didn’t have access to this second study published in 2004, but rather had to rely on an abstract that summarizes the study called Inhibition of COX isoforms by nutraceuticals. This study examined which over-the-counter nutraceuticals could inhibit, or dysregulate, COX-2 inhibitors in order to reduce inflammation.
Humans have two isoforms of prostaglandin: COX-1 and COX-2. COX-1 is cytoprotective; meaning it protects cells from harmful agents. COX-2 inhibitors reduce inflammation without the risk of ulceration and kidney damage.
The ideal nutraceutical (supplement), then, would inhibit COX-2 synthesis while preserving COX-1 synthesis.
For comparison, ibuprofen, rofecoxib, naproxen, and indomethacin were used in the study, because those drugs have known anti-inflammatory properties. Compared to the drugs, positive results were seen for the following supplements:
- Ruscus extract (also called “Butcher’s Broom), and
- Notoginseng (beware of the side effects, especially for pregnant women).
Your Takeaway On Supplements That May Reverse Aging In Humans
First off, as far as I can tell from the studies, this “reverse aging in humans” should more accurately be stated as “slow down systemic inflammation and therefore slow down aging in humans”, and I’ll take that.
In summary, I’ll do a bullet point review of the Nature study that I began this post with, and then turn to the supplements.
The Nature Study
This study shows that the development of maladaptive inflammation and cognitive decline in aging may not be a static or permanent condition, but rather that it can be reversed by inhibiting inflammatory PGE2 signalling through the myeloid EP2 receptor.
The Nature study made four claims:
- Aging is associated with a significant increase in pro-inflammatory PGE2 signalling in myeloid cells (bone marrow), which drives the sequestration of glucose into glycogen away from the generation of ATP, the compound that provides energy to drive many processes in living cells
- There’s a fundamental vulnerability of aging myeloid cells, in which they become dependent on glucose and are unable to use alternative energy sources to support mitochondrial respiration (Mitochondria are the so-called “energy factory” of cells.) This leads to a reduction of glucose flux and the development of an energy-depleted state that drives pro-inflammatory immune responses.
- By directing glucose towards the production of ATP, as opposed to glycogen storage, myeloid EP2 in aging cells is inhibited and reverts to a more anti-inflammatory state that prevents age-associated cognitive decline.
- Inhibition of EP2-dependent changes in myeloid metabolism may represent a new approach to disorders of aging, with greater specificity than the use of non-steroidal anti-inflammatory drugs that target COX-2 and COX-1 and suppress both beneficial and toxic prostaglandin signalling pathways.
The Supplements Recommended by the Studies
The two studies on prostaglandin-inhibiting supplements suggest that certain nutraceuticals may do just that, and thereby slow down the aging process; they include:
- Curcumin (see this study)
- Licorice Root
- Ruscus extract
- Notoginseng (beware of the side effects)
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