7m read|NOVOS

Altos Wants to Reverse Aging – and They Are Not the Only Ones

Altos is a company with high ambitions: they want to address aging. Even better, Altos wants to reverse aging. 

That would mean making old people younger again. 

This might sound strange or counterintuitive. 

But sooner or later, we will go toward a society where aging can be substantially slowed down and even reversed. 

People would become “ageless,” in the sense that how they look is no longer defined by their age.
  

The Road Forward for Altos

Altos recently received $3 billion in fresh funding to address aging. 

However, they are not the only company focusing on aging. 

Companies like Life Biosciences, Calico Labs (created by Alphabet), Juvenescence, and many others have received billions of dollars in investments. 

One way these companies want to reverse aging is by focusing on epigenetic reprogramming.

We at NOVOS are big believers in the promise of epigenetic reprogramming and maintaining a healthy epigenome to slow down aging.

The Epigenome: a Brief Introduction 

What is the epigenome

Very briefly, the epigenome is the intricate molecular machinery that determines which genes are switched on or off. 

The older we get, the more the epigenome gets dysregulated, meaning that some genes are turned on that should be turned off and vice versa. 

This deregulated epigenome messes up the proper functioning of cells, contributing to aging. You can learn more about the epigenome and aging here. 

A decline in the epigenome is probably one of the most important reasons why we age

Also, reprogramming the epigenome can turn almost any cell into a stem cell, or can rejuvenate old cells to a young state, as we explain here

Furthermore, the best clocks we have to measure your aging rate or your biological age are epigenetic clocks (learn more about epigenetic clocks here). 

Epigenetic Reprogramming to Reverse Aging

The way DNA (gold strand) is wrapped around histones (white structure) is one way how gene expression is regulated (Image: NOVOS)


Altos will deploy cutting-edge biotechnology to reverse aging epigenetically, for example by using Yamanaka factors (R,R). 

Yamanaka factors can turn differentiated cells into stem cells

Differentiated cells are non-stem cells that have achieved their cellular identity. Examples of differentiated cells are skin cells, liver cells, neurons, muscle cells, and so on. 

Stem cells create differentiated cells. For example, skin stem cells create skin cells, gut stem cells create gut cells, and so on. 

Scientists discovered that if you introduce four proteins (called Yamanaka factors) in differentiated cells, these cells become stem cells. For example, upregulating four Yamanaka factors (e.g., Oct4, Sox2, Klf4, and Myc) in a skin cell can turn this cell into a stem cell. 

These kinds of stem cells are called “induced pluripotent stem cells” (iPSCs).  

So Yamanaka factors induce “pluripotency” or “stemness.” “Pluripotency” means that stem cells can create all kinds of different cells. A pluripotent stem cell can create skin cells, bone cells, muscle cells, neurons, stomach cells, and white blood cells. In fact, it can create any cell in the body. 

But even more interestingly, if you periodically upregulate Yamanaka factors in a cyclical way, you can rejuvenate a differentiated cell before turning it into a stem cell (R,R). 

Whereas, turning a differentiated cell into a stem cell requires continuous activation of the Yamanaka factors, rejuvenating a differentiated cell requires only cyclical or brief activation of Yamanaka factors. 

We explain more here

Altos is exploring this “epigenetic rejuvenation.”

For this, Altos has assembled some of the world’s top scientists in this regards, like Juan Carlos Izpisúa Belmonte (an expert in epigenetic reprogramming), Manuel Serrano (also specialized in epigenetic reprogramming and senescent cells), Steve Horvath (invented various epigenetic clocks), Jennifer Doudna (received the Nobel prize for discovering CRISPR cas9 gene editing), and Shinya Yamanaka (received the Nobel prize for his discovery of Yamanaka factors to epigenetically reprogram cells into stem cells). 

These are all very impressive longevity scientists! 

A Healthy Epigenome and Aging 

The interest of longevity companies like Altos, Calico, and others in targeting the epigenome demonstrates something that we have known already for a long time at NOVOS: that maintaining a healthy epigenome is very important for health and longevity. 

That is why we have looked into various small molecules that can help to maintain or rejuvenate the epigenome. 

Of course, the technologies that Altos, Calico, and others are pursuing are far more advanced and can make a much bigger impact than oral molecules. 

However, Altos and others demonstrate the importance of addressing the epigenome for longevity. 

In nature, there are also various small molecules that you can take orally to improve the epigenome and that also have been shown to extend lifespan.

We listed the most interesting ones for you below. 

Best Epigenetic Supplements to Impact Aging

1. Alpha-ketoglutarate (AKG)

Alpha-ketoglutarate is a naturally occurring substance in our body. AKG helps to maintain the epigenome. 

For example, alpha-ketoglutarate is an important substrate of TET (Ten Eleven Translocase) enzymes, which modify the epigenome (they demethylate DNA). 

In fact, AKG plays an important role in maintaining and regulating pluripotency (stemness), something that the Yamanaka factors also do (R). 

Giving AKG to differentiated cells helps them to reprogram them into younger cells or stem cells. 

We also see in various studies that AKG improves stem cell health (R,R,R). 

We explain more about the role of alpha-ketoglutarate in longevity here.

2. Vitamin C

Many people think that vitamin C is mainly healthy because it’s an antioxidant. As we discussed before, however, many antioxidants don’t slow down aging. 

Vitamin C is not just an antioxidant; it also has various epigenetic effects (R,R). 

For example, vitamin C works together with alpha-ketoglutarate to maintain the epigenome (R). Both vitamin C and alpha-ketoglutarate are substrates for the epigenetic TET enzymes. 

It’s interesting to see that vitamin C also improves the function of Yamanaka factors during the reprogramming of differentiated cells into stem cells (R). 

3. NMN (nicotinamide mononucleotide)

NMN is a precursor to NAD. NAD is a very important molecule in all our cells, regulating cellular metabolism, DNA repair, and various other functions. 

NAD is also important to repair and maintain a healthy epigenome (R). 

4. Micro-dosed lithium

Lithium is a mineral that occurs almost everywhere in nature. Lithium has various epigenetic effects. For example, it can switch on the production of reparative proteins, especially in the brain (R,R). 

Low-dose lithium has shown to extend lifespan in animals (R,R,R,R,R) and has been associated with reduced mortality in humans (R,R), as we explain here.

5. Glycine

Glycine is a naturally occurring amino acid in our bodies. During aging, levels of glycine decline. 

It has various protective effects on cells. However, glycine can also improve the epigenome, especially in mitochondria (R). 

Glycine also plays a role in stemness or pluripotency (R). 

Glycine has been shown to extend lifespan

6. Fisetin

Fisetin is a substance commonly found in strawberries. Fisetin has various beneficial effects on the body, including reducing inflammation. It also has epigenetic effects (R,R). 

Learn more about fisetin and longevity here.

7. B vitamins 

Various B vitamins, including vitamin B9, B12, and B6, are important for proper methylation, which is the process that regulates which genes are expressed or not. 

Conclusion 

Maintaining a healthy epigenome is very important for health and longevity. 

Not only does maintaining the epigenome hold the key to slowing down aging, but actively reprogramming the epigenome can even rejuvenate the body

Maintaining a healthy epigenome can be done via various substances, such as alpha-ketoglutarate, NMN, micro-dosed lithium, glycine, and others

This is likely one reason why these substances have been shown to extend lifespan in various different organisms and experiments. 

But even when we go toward a future where aging can be partially reversed, healthy food, epigenetic supplements, exercise, proper sleep, and other lifestyle interventions will remain crucial to lead a productive, healthy, and long life. 

We explain more about epigenetic reprogramming and reversing aging here.


 

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