Biochemistry

Defeating Time: A breakthrough in Aging.

Something you can’t see or hear until years go by. Something you recognize as simple and yet impossible to avoid. Something that is known as both the cruelest and most beautiful law in all of nature. Something that neither the richest nor poorest person can escape from. That something is time. 

Throughout mankind, humans have been able to conquer just about everything, from their minuscule problems to global affairs. However, with all of our minds combined, we still failed to defeat the toughest opponent of all: time. For what seems like since the origin of the universe, it appeared as the one unstoppable force that nobody could fight.

That is until 2022. While this year beckoned the end of the COVID-19 pandemic, it also brought along news about a case study conducted by David Sinclair, a molecular biologist who spent the vast majority of his career (twenty years) searching for ways to reverse aging and undoing time in the process. While the beginning of his journey was unsuccessful, he didn’t give up. 

The study split up two different mice (siblings born from the same litter) and genetically altered one of them to make them considerably older, something that was a marked success. While this alone is not indicative of a reversal in aging, it does bring up an important question: if time could be sped up, could it also be slowed down or even undone altogether? However, before we get to that, we need to understand just how the mice were genetically altered and why. 

Image credit: https://www.cnn.com, depiction of two mice from the same litter being drastically different in age appearance.

Many believe that aging is caused due to cell damage, but that’s not exactly accurate. That is one of the reasons, yes, but that’s not the main cause. Instead, we should look at the heart of the matter: the epigenome. It is what determines what each cell becomes and how it works, an instructional manual of sorts for each cell. When the epigenome malfunctions, the “instructions” of the cells are lost, thus resulting in the cell failing to continue functioning. 

So, Sinclair utilized gene therapy to get the cells their instructions to continue working and the results were shocking. Sinclair wasn’t only able to display success in accelerating aging, but also reversing it as well by nearly 60%. What’s more, this appears to be limitless, with Sinclair even citing that “[he’s] been really surprised by how universally it works. [Him and his team] haven’t found a cell type yet that [they] can’t age forward and backward.”

This expands beyond mice: it has already been utilized to reverse aging in non-human primates through the use of doxycycline, an antibiotic with gene reprogramming potential, with rapid success. There has even been some human experimentation, with gene therapy being done on human tissues in lab settings. 

The ability to reverse aging across the board brings up more than just stopping time, it also enables the possibility of halting sickness relating to aging. In retrospect, these illnesses (like dementia and Alzheimers among others) are caused due to cell malfunction. If the reversal of aging is potent enough, it runs the risk of also undoing these illnesses. 

With the potential to halt aging and enable people to live into their hundreds without fear of age-related illnesses, it does bring up countless possibilities. If we can already undo aging on a small scale, imagine what the future ten, fifty, or even a hundred years from now can behold.

  • https://www.cell.com/cell/fulltext/S0092-8674(22)01570-7
  • https://time.com/6246864/reverse-aging-scientists-discover-milestone/
  • https://www.cnn.com/2022/06/02/health/reverse-aging-life-itself-scn-wellness/index.html

AI can now use the help of CRISPR to precisely control gene expressions in RNA

Almost all infectious and deadly viruses are caused due to their RNA coding. Researchers from established research universities, such as NYU and Columbia, alongside the New York Genome Center, have researched and discovered a new type of CRISPR technology that targets this RNA and might just prevent the spread of deadly diseases and infections.

A new study from Nature Biotechnology has shown that the development of major gene editing tools like CRISPR will serve to be beneficial at an even larger scale. CRISPR, in a nutshell, is a gene editing piece of technology that can be used to switch gene expression on and off. Up until now, it was only known that CRISPR, with the help of the enzyme Cas9, could only edit DNA. With the recent discovery of Cas13, RNA editing might just become possible as well.

https://theconversation.com/three-ways-rna-is-being-used-in-the-next-generation-of-medical-treatment-158190

RNA is a second type of genetic material present within our cells and body, which plays an essential role in various biological roles such as regulation, expression, coding, and even decoding genes. It plays a significant role in biological processes such as protein synthesis, and these proteins are necessary to carry out various processes. 

RNA viruses

RNA viruses usually exist in 2 types – single-stranded RNA (ssRNA), and double-stranded RNA (dsRNA). RNA viruses are notoriously famous for causing the most common and the most well-known infections – examples being the common cold, influenza, Dengue, hepatitis, Ebola, and even COVID-19. These dangerous and possibly life-threatening viruses only have RNA as their genetic material. So, how can/might AI and CRISPR technology, using the enzyme Cas13 help fight against these nuisances?

Role of CRISPR-Cas13

RNA targeting CRISPRs have various applications – from editing and blocking genes to finding out possible drugs to cure said pathogenic disease/infection. As a report from NYU states, “Researchers at NYU and the New York Genome Center created a platform for RNA-targeting CRISPR screens using Cas13 to better understand RNA regulation and to identify the function of non-coding RNAs. Because RNA is the main genetic material in viruses including SARS-CoV-2 and flu,” the applications of CRISPR-Cas13 can promise us cures and newer ways to treat severe viral infections.

“Similar to DNA-targeting CRISPRs such as Cas9, we anticipate that RNA-targeting CRISPRs such as Cas13 will have an outsized impact in molecular biology and biomedical applications in the coming years,” said Neville Sanjana, associate professor of biology at NYU, associate professor of neuroscience and physiology at NYU Grossman School of Medicine. Learn more about CRISPR, Cas9, and Cas13 here

Role of AI

Artificial intelligence is becoming more and more reliant as days pass by. So much so, that it can be used to precisely target RNA coding, especially in the given case scenario. TIGER (Targeted Inhibition of Gene Expression via guide RNA design), was trained on the data from the CRISPR screens. Comparing the predictions generated by the model and laboratory tests in human cells, TIGER was able to predict both on-target and off-target activity, outperforming previous models developed for Cas13 

With the assistance of AI with an RNA-targeting CRISPR screen, TIGER’s predictions might just initiate new and more developed methods of RNA-targeting therapies. In a nutshell, AI will be able to “sieve” out undesired off-target CRISPR activity, making it a more precise and reliable method. 

A solution to the Ails of Chemotherapy?

600,000 deaths. That’s how many casualties were estimated in 2021 by a foe we can’t so much as see with the naked eye: cancer. The dreaded illness that, since the foundation of modern medicine, humanity seems unable to tackle and extinguish permanently. Despite the advancement of technology (specifically in the medical sector), it seems as if we are a ways off from adequately dealing with it on a global scale. 

That isn’t to say that there aren’t methods to deal with this disease. Chemotherapy for instance is one such remedy. It decimates cancerous cells, but does so with a massive risk to the body it’s done to, through also killing the necessary (good) cells humans need in the process. This treatment results in patients becoming immunocompromised. This label not only increases the risk of people contracting diseases, but it also increases the potential for these common ailments (such as the common cold or the flu for instance) to quickly turn to a hospital visit because of a life-threatening concern. 

Described by those who administer chemotherapy as a double-edged sword, it appeared doubtful that the negative effects of chemotherapy could ever be reduced. After all, it took so long for this treatment to even be discovered according to modern medicine, reinforcing the notion that humanity’s war against cancer seems to have arrived at a stalemate.

Then came a new discovery: stem cell transplants. This method seemed to solve the problems that chemotherapy generated by administering stem cells to the vein. This enables the cells to travel to the bone marrow and then become new cells that are necessary for human health, such as platelets (which help out with blood clots), to white blood cells (which assists the immune system and helps the body fight infection) to even red blood cells (which helps facilitate oxygen throughout the body). 

Proponents of this method claim that this is an instrumental tool for humanity in its battle against cancer due to its ability to assist cancer patients after chemotherapy, which is widely considered to be the most prevalent form of cancer treatment. Although it may not be the final product, it does certainly pose questions that may pave the way toward achieving even more technological advancements in this war. 

That’s not to say that there aren’t those who are against this method however. Some argue their stance as one where this treatment excludes the common man: stem cell transplants are incredibly expensive due to their highly advanced technological nature. This high price tag prevents the vast majority of cancer patients from being able to access this potentially life-saving treatment, pushing the ethical dilemma concerning both wealth and the ability to save a life (if not multiple). Others who are against this cite that it too comes with some drawbacks much like chemotherapy in the form of side effects. From bleeding to increased risk of infection (which is what it’s partially designed to combat), it too poses a set of risks that cannot be ignored in the eyes of some. 

Image credit: bioinformant.com, depiction of stem cells.

Regardless of your stance on this matter, there is a middle ground: this innovation, despite all of its shortcomings, has advanced the battle against cancer in many ways beyond just one. Beyond helping people achieve some sense of normalcy in their lives through alleviating the impacts of chemotherapy, it also grants hope to those who have (or can obtain) access to this treatment. Modern medicine, just like how it conquered measles and rubella and countless other diseases, will hopefully beat this one too.

  1. https://www.cancer.gov/about-cancer/treatment/types/stem-cell-transplant
  2. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2021.html