• The discovery of ways to induce pluripotency of stem cells has allowed the advancement of stem cell, embryo, and organoid research.
• However, while pluripotency can be induced, the reversal of aging has proved more difficult.
• A group of researchers has claimed to have discovered cocktails of chemicals that reverse aging in cells.
• According to other researchers, the markers used to measure this could be an important breakthrough.

One of the most significant breakthroughs in biology in the past 2 decades was the discovery of how to induce stem cells to regain their pluripotency.

Stem cells are cells that are able to change into many different cells, and this process allows cells and tissues in the body to replace cells that have died or create cells needed in response to certain conditions, such as immune cells.

Being able to return differentiated cells to their previous pluripotent state and create induced pluripotent stem cells (iPSCs) was first achieved by Prof. Shinya Yamanaka in 2006, and saw him and Sir John B. Gurdon awarded the 2012 Nobel Prize in Physiology or Medicine for their breakthrough.

Since then, understanding how to create induced pluripotent stem cells has been harnessed to allow for the development of embryo models to allow us to study the very earliest stages of human development and develop organoids for research into different conditions.

Can we really measure age accurately?

Despite the ability to make individual cells return to a state of greater pluripotency, returning cells to a younger state has proved challenging.

This is partly because the concept of an organism’s biological age and how that age affects it at the cellular level is complex and depends on many factors.

Telomeres are a segment of DNA at the end of a chromosome that shortens each time a cell divides, meaning the older an organism, the shorter the telomeres in its cells are.

Methyl groups are a molecule found attached to DNA that plays a role in how it is read by the cell machinery. The configuration of these molecules, known as epigenetics, can change with age.

In fact, epigenetic clocks have been developed, such as GrimAge, which purport to be able to provide a “biological” age for humans, not based on chronological age. It has been used to suggest that stress can accelerate aging.

Recently a team of researchers from the United States and Russia developed an “aging clock” based on information they had gleaned on age-related gene expression changes they had quantified from studies.

They used this transcription-based aging clock to demonstrate that cell reprogramming had occurred following genetic engineering to knock out and overexpress genes associated with aging. Their findings are published in a preprint version, which has not yet undergone peer review.

6 chemical cocktails to reverse aging?

More recently, the research team used this same “transcriptomic aging clock” to demonstrate that genes they had found to be associated with aging were downregulated in cells that had been treated with one of six chemical cocktails, in a paper published in the journal Aging, led by Prof. David Sinclair, a professor in the Department of Genetics at Harvard Medical School.

This paper also demonstrated that as cells age, the nucleus of the cell becomes leakier, meaning that the more molecules that are normally found in the cell nucleus are found in the rest of the cell, the older the organism the cell is likely to be from.

Researchers used a fluorescent marker to measure the nuclear barrier’s breakdown to determine the cell’s age.

Dr. Zachary Harvanek, instructor of psychiatry in the Yale Department of Psychiatry, who has carried out research into the impact of aging on epigenetics, but was not involved in this study, told Medical News Today in an interview:

“I think the biggest advance in this paper is the method for quickly testing these drugs in cell culture. I think that could be a quite important development in terms of being able to discover new medications, or new drugs that might be useful.”

Claims of turning back the clock by 3 years

The researchers who conducted the recent study exposed skin cells in the laboratory to cocktails of chemicals that had already been shown to have an effect on the transcription of genes associated with aging. Compounds included valproic acid, which is used to treat epilepsy and other neurological and psychiatric conditions.

They claim their results demonstrate that the age of cells exposed to the chemical cocktails was reversed by 3 years in 4 days, which previously has only been demonstrated with over a year of regenerative treatment in humans in previously published studies.

However, these experiments were not carried out in humans and instead were carried out in the lab. These cells were taken from a 22-year-old donor, a 94-year-old donor, and a patient with an aging disease known as progeria. Information on their sex and ancestry, which could affect findings, were not included in the paper.

Can these findings be applied to humans?

Dr. Xiaojing Yang, principal investigator of the Yang Laboratory at the University of Illinois Chicago, who was not involved in the research but co-authored a paper with Prof. Sinclair earlier this year, told MNT in an email: “This is a good initial study and something we will follow with interest, but concerning the claims about reversing aging by 3 years in 4 days, it’s crucial to interpret these results within the context they were generated.“

“This study used a cell culture model to screen for potential anti-aging compounds, which is a fundamental part of the drug development process,“ she explained. “That said, it’s important to remember that the transition from successful in vitro results to effective therapies in humans is a long and uncertain path.“

“So, while this research is an exciting step in the study of aging, it’s just one piece of a complex puzzle. More research and validation, especially in whole organisms, are needed before these findings can be translated into practical anti-aging interventions,” said Dr. Yang.

Dr. Harvanek echoed this sentiment and added: “I think the finding that this specific cocktail seems to reverse aging in cell culture is a very preliminary finding. I don’t think there is any evidence right now that this is going to reverse aging in humans or other animals.“

“So I think the methods they use are the biggest takeaway from this paper and not necessarily the subsequent findings,” he emphasized.

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