This Breakthrough Could Change Aging Forever & Why You Could Be Missing Out

This could be the biggest leap in anti-aging—why you’re not in on the secret.

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My Longevity Experiment
August 22, 2024

This Breakthrough Could Change Aging Forever & Why You Could Be Missing Out

This could be the biggest leap in anti-aging—why you’re not in on the secret.

This is a review of the article ‘Another Win for Senolytics: Fighting Aging at the Cellular Level Just Got Easier’ by Shelly Fan PhD and some other interesting information on senolytic trials.

In the article Shelly references the parable of the blind men and the elephant and likens it to Longevity. For those unfamiliar with the parable, in essence blind men who don’t know what an elephant is are asked to touch a different body part and then conceptualize what the animal is like, because of their limited experience and specific area of touch, each man has vastly different conclusion and they all believe that they’re description is correct.

She proffers that aging, thanks to its complexity, is the bio-medical equivalent of the elephant. In that researchers have focused on either one or another “hallmark” of aging, with some success, but not a number together.

Joining the Dots

For example, past research has shown us that energy production in our cells can become erratic and non-functional as we age. Cells programmed for apoptosis don’t die, but instead become zombie-like senescent cells.

A senescent cell is a cell in our body whose telomeres have reached their "Hayflick Limit" i.e. its telomeres have become so short that the cell cannot divide anymore. It is not a healthy cell anymore, it’s not exactly dead, but it is programmed for death, this cell death is called apoptosis, the Greek for self-eating, if it doesn’t die it starts to produce chemicals that increase inflammation and damage our DNA.

The key is to find out how other hallmarks of aging, such as lower NAD, inflammation and shortening telomeres interact with zombie cells, so we can see the whole picture.

The Study

A new study published in Nature Metabolism has started to connect the dots. A study, in mice, linked up three promising anti-aging pathways:

  • Attacking senescent cells

  • Addressing inflammation

  • Tackling unreliable energy production in cells

All three elements point to one key factor that drives aging. Let’s look at each in turn.

Healthy to Zombie Cell

Shelly likens individual cells to small cities; each with their own power plants and their ‘superstar’ molecular worker is Nicotinamide Adenine Dinucleotide (NAD). As we know NAD is a molecule that’s critical for helping mitochondria produce energy.

As we age our cells start losing NAD and with this reduction our mitochondria become less able to produce the energy we need, which in turn flips normal cellular function into dysfunction.  At present this hypothesis has only been prove in mice.

One dysfunctional element is that cells programmed to die through apoptosis don’t die, are not consumed by the body as extra fuel, but instead hang-around as senescent or zombie cells.

These zombie cells then turn to the dark side and start to leak an inflammatory cesspool of molecules called Senescence Associated Secretory Phenotypes (SASP) that “spread” harm and injury to adjacent healthy cells.

Senolytics

Senolytics are a group of compounds that destroy these “zombie” cells. A study in old mice, the equivalent of a 90-year-old human, found that wiping out these zombie cells with two simple compounds increased their lifespan by nearly 40%.

Others using a genetic “kill switch” in mice found that destroying just half of their zombie cells helped the mice live 20% longer and also allowed them to have healthier kidneys, stronger hearts, more luscious fur, and higher than normal energy levels.

In the same way that some companies now sell NAD boosters like NMN and NR, pharmaceutical companies are investigating over a dozen potential senolytics in a race to bring one to market. But is two better than one, could NAD boosters and senolytics be combined?

The Buck Institute

A new study, led by Dr. Judith Campisi and Dr. Eric Verdin at the Buck Institute for Research on Aging in California, asked if the lines between lower NAD and zombie cells could be connected, and added could the connection be CD38? CD38 wreaks havoc by both boosting inflammation and destroying our beloved NAD.

CD38 Study

Using tissue from mice and humans, the team traced CD38 to a type of immune cell. These cells, called M1 macrophages (which literally means, ‘big eaters) are well known to increase inflammation in the body and cause DNA damage as we age.

When comparing fat tissue isolated from young and old mice, the team realized that M1 macrophages relentlessly pump out CD38 as the cells age, which in turn, breaks down the much-needed NAD.

Dr. Eric Verdin used the analogy of a sink and water source saying, “Do NAD levels drop because of a faucet problem, i.e. our ability to make NAD, or is it a leaky sink problem, where aging cells break down NAD too fast.

Our data suggests that, at least in some cases, the issue stems from the leaky sink. Which to me means we can make NAD okay; it’s just that it runs out before we can use it.”

The Zombie Connection

This is what we know so far: aging triggers immune cells that pump out CD38, a chemical that destroys our NAD.  But how can we stop CD38?

In an unexpected twist of events, the connection actually seems to be the zombie cells. Remember, zombie cells leave a chemical evidence trace called Senescence Associated Secretory Phenotypes (SASP). They also change their ‘molecular structure’ so it’s possible to separate them from the healthy cells.

In the fatty tissue gathered from aged mice, the team identified zombie cells and found that their “toxic waste” vastly increased the amount of CD38. So, it is the Senescence Associated Secretory Phenotypes (SASP) that direct the immune cells to make more CD38.

Testing the Theory

If zombie cells are the directors, then getting rid of them should reduce CD38 and in turn, preserve our NAD; well, that’s the theory. To test it, the team used genetically engineered mice; this allowed the scientists to identify the zombie cells and then selectively kill them.

The team injected the mice with a drug that damaged their DNA. This mimicked aging, in the sense that it increased zombie cells and CD38. Result, killing the zombie cells lowered CD38 levels, which in turn preserved NAD.

Statement

Dr. Verdin said, “We are very excited to link two phenomena which have been separately associated with aging and age-related disease. For now, zombie cells seem to be a master-level culprit that drives inflammation, decreases NAD levels, and breaks the cell’s energy production.”

This suggests that senolytics, which selectively kills off zombie cells, could as a secondary effect also increase NAD, something we didn’t know previously.

NAD Boosters

On supplementation Dr. Eric Verdin said, “Ultimately I think supplementation will be part of the equation, but filling the sink without dealing with the leak will be insufficient to address the problem.”

In other words, for NAD supplementation to work more efficiently, we may need to also use senolytics drugs to decrease zombie cells and CD38 levels; in essence plugging the leak in the sink, before we turn the NAD tap on.

Where to get Senolytics?

In an article posted in the US National Library of Medicine, it states that senolytics are a class of drugs that selectively clear senescent cells. The first senolytic drugs are:

  • Dasatinib (approved in the USA and EU as a leukemia treatment)

  • Quercetin (a plant Flavanol available in supplement form)

  • Navitoclax (an experimental anti-cancer drug)

  • Fisetin (a dietary Flavonoid available in supplement form)

Early pilot trials of senolytics suggest they decrease senescent cells, reduce inflammation and alleviate frailty in humans.

Clinical trials for diabetes, idiopathic pulmonary fibrosis, Alzheimer’s, COVID‐19, osteoarthritis, osteoporosis, eye diseases, bone marrow transplants and childhood cancer survivors are either underway or just beginning.

Study Links: