Chemically Reversed Aging is The New Black

My Chemical Romance (For Anti-Aging) ⏰

Big news. A game changing study just cranked up the speed on our race to find the fountain of youth. The lads over at Harvard Medical School, the University of Maine and MIT, have done something big.

They’ve found a way to not only slow cellular aging, but also reverse it, chemically.

Previously, reversing cellular aging was only possible through potent gene therapies. But now, in a study published on July 12, 2023, "Chemically induced reprogramming to reverse cellular aging", the team offers us a whole new path to get the job done chemically, in a very short period of time.

They have identified six chemical cocktails that restore nucleocytoplasmic protein compartmentalization (fancy term for the distribution of proteins between the nucleus and the rest of the cell) and genome-wide transcript profiles to their youthful states.

In simpler terms, they've found a chemical solution to make our cells act young again, and it takes less than a week to do it.

Before this, the same team had used specific genes (Yamanaka genes, for those in the know) to successfully turn back the cellular clock. This proved the concept, but using gene therapy to reverse aging is a costly and lengthy process. The new chemical approach brings the potential for faster, more accessible age reversal.

Something they were worried about was reversing the cellular aging but also stopping the reversal process as once a cell becomes “too young” it can become cancerous. This was something they were able to avoid.

David A. Sinclair (I have a feeling you’re going to start seeing this guy a lot - remember him from when we talked about NMN?), the project's lead scientist, envisions a future where the dream of whole-body rejuvenation is a reality. "This new discovery offers the potential to reverse aging with a single pill, with applications ranging from improving eyesight to effectively treating numerous age-related diseases," he shared.

Human trials of this age reversal gene therapy are already underway, hot on the heels of successful trials that reversed blindness in monkeys. As Sinclair said, "Until recently, the best we could do was slow aging. New discoveries suggest we can now reverse it."

What are Yamanaka Factors?

Yamanaka factors are a set of four specific genes that can "reset" an adult cell back to its earliest form, which is a stem cell. The process is a bit like turning a fully grown tree back into a seed. This is important because stem cells are like blank slates that can grow into any type of cell in the body, which has significant implications for disease treatment and understanding the aging process.

These factors are named after Shinya Yamanaka, the scientist who discovered them, and his work on these factors won him the Nobel Prize in 2012.

Too Many Big Words - How’s this all work?

Imagine life as a giant storage box. In it, you have two main types of information - the genome and the epigenome. The genome is like a cookbook that stays the same throughout your life, and it contains all your recipes (genetic information). The epigenome, on the other hand, is like a half-drunk sous-chef. It helps execute those recipes, but it can also switch them up, changing with your environment and over time.

As we age, there are certain signs (or "hallmarks") that pop up, kind of like your car's "check engine" light. One of the main culprits? The sous-chef is losing its touch - epigenetic information gets lost and cells start to forget who they are. This triggers a series of negative events, kind of like dominos toppling over, leading to aging and age-related diseases.

Ever heard of cells retiring? That's a thing. It's called cellular senescence. These cells stop dividing and start releasing a bunch of inflammatory stuff. Over time, too many of these retiree cells lead to age-related diseases, like macular degeneration and increased blood pressure.

Enter a quartet of heroes: OCT4, SOX2, KLF4, and c-MYC, fondly known as "Yamanaka factors". These guys can make cells forget their job and turn them into "anything-can-be" cells, aka stem cells. However, using all four of these factors was like turning the dial up to 11 - it was too much and could lead to uncontrolled cell growth which can turn the cells cancerous (not a good thing).

But, scientists discovered that by using just three of these factors (OCT4, SOX2, and KLF4, minus c-MYC), they could rejuvenate cells, improve tissue function, and even extend lifespan without the risk of cancer. Kind of insane to think about.

The problem? Right now, to deliver these factors, we need to use methods that can be expensive and potentially risky.

So, in this study, they used new testing methods to find chemical mixes that could do the same job. It's like cooking the same dish but using a different recipe. Their results? Just as delicious. They were able to rejuvenate cells and reverse aspects of aging without erasing cell identity, and they did it chemically rather than genetically.

Translation: We're one step closer to an affordable, safer, and chemically driven fountain of youth.

What does the future of this research look like?

So, imagine having a magic pill that could wind back the clock on your cells, making them act younger, fresher, and more efficient. That's essentially the potential of this research.

In terms of medicine, the implications are staggering. We're talking about a whole new approach to treating aging and age-related diseases. Imagine being able to regenerate tissues that have been damaged by injuries, age, or diseases like Parkinson's or Alzheimer's. Or think about conditions related to aging like heart disease, arthritis, and even vision loss. They could all potentially be addressed in new ways thanks to this breakthrough.

It's not just about treating diseases, either. It's also about preventative medicine. By keeping our cells in a 'younger' state, we could potentially delay the onset of many age-related conditions and improve the overall quality of life as we get older.

And let's not forget the potential for whole-body rejuvenation. We're not quite in the realm of science fiction, where you could pop a pill and wake up looking twenty years younger. But on a cellular level, this kind of rejuvenation could make our bodies function more like they did when we were younger, which would be a significant leap forward.

We might have to get rid of the phrase, “I’m too old for this shit”.

As for the next steps, the researchers will be working on fine-tuning their approach. They've found six chemical cocktails that work in the lab, but there's a long road ahead before these could be used in human treatments. The safety and efficacy of these cocktails need to be tested thoroughly. Plus, scientists need to understand better how these chemicals are working on a molecular level.

That’s a little above my paygrade but it’ll be awesome to watch Dr. Sinclair and his gang of longevity nerds play god over the next few decades.

Also, the researchers have to ensure that any treatments developed from this research are cost-effective and accessible. Developing a chemical alternative to gene therapy could reduce costs and speed up the development process, making treatments more widely available.

And of course, human clinical trials are on the horizon. They've seen positive results in animal trials, including reversing blindness in monkeys, and this paves the way for human trials.

In a nutshell, this is a huge step forward in the fight against aging and age-related diseases. As someone who’s watched family members struggle with dementia and Alzheimer’s, it’s pretty fucking fascinating.

We're still some way off from seeing these treatments in our local pharmacy, but I’ll be damned if I’m not interested to see how this shit shakes up.

Wishing you a productive rest of your week.