Aging and cancer are deeply interconnected.

To oversimplify (because otherwise each bullet point would be the size of a large library):

• Cellular aging is in large part a matter of DNA damage, copying errors, errors beyond copied forwards, exacerbating the problem
  • That latter item, by the way, is one of the reasons why sometimes a lot of aging seems to arrive all at once in a burst; it’s because once a DNA copying error is made, it gets copied forwards and proliferated rapidly. On which note…
• Cancer is in large part a matter of DNA damage that specifically made the cell line accidentally immortal (sounds good, is very bad), and then it gets copied forwards and proliferated
  • Which can kill you, because you’re only supposed to have so many cells there (they’re supposed to die at approximately the same rate that they’re made, and instead they’ve stopped dying and they’re proliferating exponentially) so what you end up with is exponentially increasingly many cells that are still using the resources from the still-working cells around them, and/but doing nothing but growing an ever-increasing tumorous mass that, depending on where it is, might kill you directly (by pressure against an organ, especially if it’s the brain) if the systemic exhaustion and/or indirect organ failure doesn’t get you first.

The good news is that this means that many things that are anti-aging are also anticancer.

The bad news is that this isn’t always so!

Polyamines: for better or for worse, in sickness or in health?

We’ve written about polyamines before, and their role in healthy longevity, for example: Spermidine For Longevity

And, for that matter: Spermine vs Alzheimer’s & Parkinson’s!

However, scientists (Dr. Keiko Kashiwagi et al.) have investigated why these longevity-inducing compounds are also consistently elevated in cancer cells (remember, cancer cells are terribly long-lived, being in fact biologically immortal!).

Firstly, we need to understand what polyamines do in healthy cells: polyamines act as “geroprotectors” by stimulating autophagy*, the cellular recycling process, primarily through activation of a specific protein (known to its friends by the snappy name of “eIF5A1”), which supports mitochondrial function and healthy aging.

*We wrote about this here: Fisetin: The Anti-Aging Assassin ← so-called because it works by killing the aging cells that need to die sooner rather than later if aging is not to be exacerbated by copying their mistakes forwards

What Dr. Kashiwagi and her team found, using high-resolution proteomics across more than 6,700* proteins in human cancer cell lines, was that polyamines first and foremost boost glycolysis—rapid glucose breakdown for energy—rather than mitochondrial respiration. In other words, reinforcing a metabolic pattern typical of cancer cells.

^{*The paper says “>6,700”, and links to a database. Wanting to know the precise number to tell you, we went to look at the database. It took a long time to download, and well, it’s an Excel spreadsheet with 60 columns and 96,294 rows. We’re keen to go the extra mile at 10almonds, but even we have our limits, so we will tell you the number is somewhere between 6,700 and 96,294. It’s a lot.}

Back to the concepts rather than the numbers: this difference (favoring glycolysis vs mitochondrial respiration) becomes a problem, because… Well, you remember our dear friend eIF5A1?

It has a sneaky sibling, eIF5A2.

Now, while eIF5A1 supports autophagy and mitochondrial health in normal cells, this closely-related eIF5A2 protein—sharing 84% of its amino acid sequence—is selectively increased in cancer cells and, as an encore, drives tumor-promoting gene expression.

You can read the paper itself, here: Polyamines stimulate the protein synthesis of the translation initiation factor eIF5A2, participating in mRNA decoding, distinct from eIF5A1

So, what does this mean, in practical terms?

The researchers suggest that targeting eIF5A2 or its interaction with ribosomes could provide a selective cancer therapy strategy, potentially blocking tumor growth without disrupting the beneficial eIF5A1-mediated effects linked to healthy aging.

But that’s not very useful on an individual level.

Instead, what we might do is draw from conclusions about the use of other senolytics—compounds that increase autophagy and thus improve healthy longevity by killing “zombie cells” that otherwise were overdue for dying.

For example, in this: The Drug & Supplement Combo That Reverses Aging

In this case, the researchers found that the senolytic compounds were best taken not daily, but rather once every two weeks.

Why? So that the body’s normal tumor-suppression systems can be working most of the time, and the senolytic does a clearing-out of old cells once every two weeks, which is a one- or two-day purge, not long enough for any cancer to get a foothold before the normal tumor-suppression systems come back online.

Want to learn more?

You might enjoy:

Fasting Cancer – by Dr. Valter Longo

Take care!