Blueberries won't make you live longer
Why antioxidants don't work, New Spin to the free radical theory of aging
Hi, I’m Aastha, and welcome to Live Longer World, where I interview scientists researching the frontiers of longevity science and write about health & longevity practices.
Many of the ideas presented in this essay are from Dr. Nick Lane’s (scientist and author of many popular prize-winning science books) book Vital Question: Energy, Evolution, and the Origins of Complex Life.
Alas, antioxidants don’t work
For years, popular media has told you that eating plenty of antioxidants is the secret to longevity. Stock up on those blueberries and Vitamin C. Yet, we haven’t cracked Methuselah’s code with this apparently neat hack. Antioxidants, so it was believed, can counter the accumulation of free radicals in our body, which over time cause damage and aging. The problem is that the science on this has been debunked, however, popular media has not reversed its stance. Luckily, it’s not a hefty crime as blueberries and Vitamin C in the right doses are healthy for you. However, the idea that large or even small doses will make you live longer by combating free radicals is dubious at best.
Free radical theory of aging
The myth of blueberries extending lifespan comes from the free radical theory of aging. Free radicals and reactive oxygen species are unstable molecules with unpaired electrons that are primarily produced in the mitochondria as a byproduct of cellular respiration. During cellular respiration, mitochondria produce energy (ATP) by transferring electrons through the electron transport chain. Some electrons "leak" and react with oxygen, forming free radicals. They are highly reactive and readily interact with nearby molecules like DNA, proteins, and lipids, causing “oxidative damage.”
It was believed that over time the damage from these free radicals surpasses the body’s ability to repair itself. This results in damage to DNA, proteins, tissue and organ functioning, all of which result in aging.
Debunk the free radical theory of aging or a new twist?
The free radical theory of aging has not withstood testing. While free radicals often rise with aging, the case for free radicals causing aging has not been established. Even better, there is no clear evidence to show that antioxidants increase lifespan. In fact, high doses of antioxidants might come with a level of risk for reasons we’ll discuss below. Dr. Nick Lane says in the book Vital Question “Many long-lived animals have low levels of antioxidant enzymes in their tissues, while short-lived animals have much higher levels.”
If all this is true, should the free radical theory of aging see the grave? Many gerontologists do consider it to have found its grave. However, Nick Lane has a more subtle version of the free radical theory of aging which is worth taking seriously. Instead of the graveyard, perhaps a different explanation is warranted.
A new spin to the free radical theory of aging
(If easier, I have a diagram flow chart below which easily summarizes and explains this theory)
The old theory said that free radicals are bad for us, and if we can reduce the number of free radicals using antioxidants, then we can slow aging. But biology is not as black and white as this theory makes it sound. Many biological reactions and molecules have a dual effect – they can be beneficial and harmful at the same time. For example, we know how Vitamin D is useful for us, but in large quantities it can be harmful.
It’s important to recognize that free radicals are not all bad. They serve 2 very important functions in the body:
Signaling to cells to optimize respiration (Free radicals are released when respiration is not optimal. Free radicals tell the mitochondria to make more copies of itself to increase mitochondrial capacity and allow for optimal respiration).
Apoptosis (cell death) of deficient cells.
What causes respiration to not be optimal?
Free radicals are released when respiration is not optimal. But what causes sub-optimal respiration?
When there is a respiratory deficit - demand for respirations exceeds supply.
Mitochondrial DNA is incompatible with the nuclear DNA - Mitochondria are the only organelles in human cells that have their own DNA outside the nucleus. As a result, there are sometimes compatibility issues between the nuclear DNA and mitochondrial DNA, both of which have to cooperate to carry out bodily functions.
When there is a respiratory deficit, free radicals signal to the cell to correct this deficit by increasing mitochondrial capacity. As a result, the mitochondria that release the most free radicals will make the most copies of themselves. Note how free radicals are not “bad” in this case - they are a signal to the body to make more mitochondria, which is great if the mitochondria are healthy.
Let’s look at the 2nd reason for sub-optimal respiration in more detail.
Mitochondria DNA incompatible with nuclear DNA
The reason for sub-optimal respiration could be the mitochondria’s incompatibility with the nucleus. In this case, the most incompatible mitochondria produce the most free radicals, and hence make more copies of themselves. (Remember: free radicals are a signal to fix sub-optimal respiration by making more copies of the mitochondria). This would result in an increase in incompatible mitochondria or mitochondria with a lot of mutations. An increase in mitochondrial mutations, could result in the cell dying by apoptosis (cell death). However, in some cases the cell might not die.
When a cell with mitochondrial mutations dies by apoptosis
If the cell dies by apoptosis, it may or may not be replaced. If the cell is replaced by a healthy cell, life is good. If the cell is not replaced, fewer cells remain to do the same job, and they have to bear more of the burden. This might result in them becoming physiologically stressed resulting in changes to gene regulation or loss of tissue, and hence aging.
When a cell with mitochondrial mutations does not die by apoptosis
In this case, even though the cell has a large presence of incompatible (damaged) mitochondria (each cell has hundreds of mitochondria), the cell does not die by apoptosis. If the energy needs of the cell are less, it can be met by deficient mitochondria. However, a large presence of deficient mitochondria might cause the cell to become senescent, leading to inflammation, and in extreme cases, cancer.
Summary: Aging when Mitochondrial DNA is incompatible with Nuclear DNA
To summarize, sub-optimal respiration might be due to the mitochondria being incompatible with the nucleus. Free radicals are released as a signal to the mitochondria to make respiration optimal by making copies of itself. However, more copies of incompatible mitochondria are not good. It means more copies of mitochondria with mutations.
A large presence of incompatible mitochondria might result in cell death. If cell death is replaced by new healthy cells, then it’s fine. But, for whatever reason, if new cells are not formed, then fewer cells remain in the body resulting in loss of tissue and aging.
According to this new spin, aging is because:
Damaged cells die and are not replaced by new healthy cells. It results in fewer cells, loss of tissue and more stress to the remaining cells.
Damaged cells don’t die. They cause inflammation and potentially cancer.
Free radicals are not the cause of aging. They merely signal damaged cells in some cases.
Conclusion
Note how this spin to the free radical theory of aging contrasts with what was previously thought. The conventional view is that free radicals cause oxidative damage leading to aging. However, this version of the free radical theory of aging does not invoke free radicals to be the causal factor in aging. It says that free radicals are a signal when there is an energy deficiency and that something could be wrong in the body. And this energy deficiency could be due to imbalance in supply and demand or due to existing damage to mitochondria. Free radicals play a role in apoptosis to kill the damaged cell, but this results in tissue loss which builds up over time and causes aging.
We conflated free radicals being a signal for poor health with free radicals being the culprit of poor health. In fact, as noted above, free radicals are helpful in signaling to the body to make respiration more optimal and to kill cells when they are unhealthy.
This is why targeting free radicals with antioxidants does not work. Free radicals are not the cause of the problem, they are signals that there could be a problem.
If you have any thoughts on this post, I’m curious to know - please write to me or comment!
To living longer,
Related: This post ties in to the metabolic theory of cancer which states that cancer is caused damage to the mitochondria. See my interview with Dr. Thomas Seyfried to learn more.
Manage Cancer Without Chemo & Radiation | Dr. Thomas Seyfried
Hi, I’m Aastha, and welcome to Live Longer World, where I interview scientists researching the frontiers of longevity science and write about health & longevity practices.