A team of scientists from Harvard Medical School said they discovered a novel chemical approach to rejuvenate and reverse aging in cells, without causing cells to become too young or cancerous. They said they screened for effective anti-aging molecules and found six chemical combinations to be successful. They said that three of the combinations (C1, C2, & C3) reduced the age by more than three years after only four days of treatment.
* Please note that I am just sharing the details, based on the information Sinclair provided online and in the research paper. There are people who are voicing objections to the claims that have been made surrounding this study. I’m not sharing any opinions on that in this post, but I just want to be clear that I am sharing what they presented and a short break down of the details of the study for anyone who is interested.
Their study builds upon prior research involving the Yamanaka Factors, which are a set of genes that play a vital role in the creation of induced pluripotent Stem Cells (iPSCs), which are cells that have the ability to become any cell in the body.
Here you can see David’s first post about it on Twitter, where he’s sharing the news of the study –
Researchers said they created new advanced screening tests using human cells in order to identify molecules that are capable of reversing the aging process and revitalize cells, without making alternations in their genetic material. If true, then they can use this technology to continue testing on other molecules in future studies.
Through the use of their novel screening tests, they said they discovered that six chemical cocktails were successful and had a significant impact on cells, reversing their age. Additionally, there was a reversal in their genome-wide transcript profile, meaning their gene expression patterns that are associated with cellular aging were reversed.
The Yamanaka Factors
According to the study, the researchers wanted to use chemical methods for age-reversal and didn’t opt for methods such as delivering RNA through lipid nanoparticles or using adeno-associated viruses to deliver DNA. They decided to develop a chemical alternative due to potential barriers of the technology being widely used, if they had opted for genetic means of delivery. They cited costs and safety concerns as issues.
To understand why they wanted to use a chemical option for age reversal, it helps to understand a little background on this research that they’re building upon, which involves the Yamanaka Factors; a set of genes that were discovered in 2006. These genes are said to play a key role in aging, and they’re called the OSK Genes. They are said to play a vital role in the creation of induced pluripotent Stem Cells (iPSCs), which are cells have the ability to be converted into any cell in the body.
In a video interview with Sinclair on the topic of the Yamanaka Factors, he said, “We discovered three genes in particular that were very safe to reverse aging by about 60-75%.” * Note: I cannot find any research to back this claim, but if you know of any, please share it in the comment section.
Sinclair said its previously been shown that the induction of the Yamanaka factors OCT4, SOX2, and KLF4 (OSK) in mammals can restore youthful DNA methylation patterns, transcript profiles, and tissue function, without erasing cellular identity.
The chemical cocktails they discovered in the study were capable of reversing cellular age in a way similar to OSK over-expression, according to the study. “Thus, it is possible to reverse aspects of aging without erasing cell identity using chemical rather than genetic means,” according to the study.
According to the study, “Expression of OSK throughout the entire body of mice extends their lifespan. Together, these results are consistent with the existence of a “back-up copy” of a youthful epigenome, one that can be reset via partial reprogramming to regain tissue function, without erasing cellular identity or causing tumorigenesis.”
By testing out over 80 chemicals, they said they found six chemical combinations or cocktails that were able to reverse and rejuvenate cells, essentially resetting their age. Additionally, they created novel screening methods which may help in future studies.
According to the study, “This advancement might enable the treatment of various medical conditions and potentially even facilitate whole-body rejuvenation.” This opens the door to future research.
- These tests were designed to differentiate between young, old, and senescent cells. There were numerous tests done, which involve the use of transcription-based aging clocks, and a real-time nucleocytoplasmic compartmentalization (NCC) assay.
- The purpose was to identify small molecules which are capable of reversing the effects of aging and senescence. Senescence is a state in which cells cease to divide and enter a state of permanent growth arrest, but they don’t necessarily die.
Additional studies are in progress to understand the mechanisms behind cellular age reversal with chemicals. These follow-up studies aim to investigate how cells are able “reset cellular age” by “writing” and “reading” a “backup copy” of earlier epigenetic information.
“The observation that genetic and chemical rejuvenation of cells is possible, restoring earlier gene expression patterns while retaining cellular identity, indicates that old cells possess information to reset their biological age, consistent with the Information Theory of Aging. Identifying how this putative information is encoded and where it resides will greatly speed the development of increasingly effective approaches to rejuvenate cells,” according to the study.
DISSENTING OPINIONS FROM OTHERS IN HIS FIELD
There has been push-back from other experts in this field. Dailymail.com conducted an interview with Matter Kaeberlein, a biogerontologist, and he said, “The screening method here is innovative and could lead to important discoveries one day, which is why I say the study is preliminary. These cocktails they describe here might even have useful therapeutic properties. But there is no direct data in this paper providing evidence for such. They should have validated at least one of these cocktails in an animal and shown improvements in age-related health metrics or lifespan before making these claims about effects on biological aging.”
Dr. Charles Brenner, a metabolism researcher and Chief Scientific Advisor at Chromadex, a company which sells Nicotinamide Riboside under the brand Tru Niagen, had a lot to say about this study. But, he has a history of pushing back against David Sinclair and his findings –
João Pedro de Magalhães, a Portuguese scientist who studies aging through computational and experimental approaches, also had something to say about Sinclair’s study and you can see their Twitter exchange here –