The development of stem cell, embryonic development, and organoid research has been made possible by the discovery of methods to make stem cells pluripotent.

Pluripotency can be created, however it has proven more challenging to reverse ageing. A team of scientists claims to have found chemical concoctions that can stop cells from ageing.

Other researchers believe that the markers employed to measure this could represent a significant advance.

The discovery of how to cause stem cells to restore their pluripotency was one of the most significant developments in biology in the previous 20 years.

Because stem cells can differentiate into a wide variety of other cells, the body’s cells and tissues can replace dead cells or produce new cells as needed, including immune cells, in response to various situations.

Prof. Shinya Yamanaka and Sir John B. Gurdon were jointly given the 2012 Nobel Prize in Physiology or Medicine for their discovery of how to produce pluripotent stem cells (iPSCs) from differentiated cells. This work was originally accomplished in 2006 and led to the creation of induced pluripotent stem cells.

Since then, developing embryo models has enabled us to investigate the very earliest phases of human development and generate organoids. This has been made possible by the knowledge of how to create induced pluripotent stem cells.

Can age be quantified accurately?

Restoring cells to a younger state has proven difficult, despite the capacity to induce individual cells to return to a more pluripotent state.

This is partially due to the complexity and interdependence of the idea of an organism’s biological age and how it affects on it at the cellular level.

Each time a cell splits, telomeres, a section of DNA at the end of each chromosome, are shorter, therefore the older an organism gets, the shorter the telomeres in its cells are.

DNA has a substance called a methyl group attached to it that affects how the cell’s machinery reads the DNA. Age can affect these molecules’ epigenetic conformation, which can alter.

Epigenetic clocks, like GrimAge, claim to be able to determine a human’s “biological” age, which is independent of their chronological age. It has been claimed that stress can quicken aging.

A group of scientists from the US and Russia recently created an “aging clock” using data on age-related gene expression variations that they had quantified from studies.

They employed their transcription-based ageing clock to show that cell reprogramming had taken place after aging-related genes were overexpressed and knocked off by genetic engineering. Preprint versions of their findings, which have not yet been subjected to peer review, are published.

Six chemical concoctions to stop the ageing process?

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

This study also showed that as cells age, their nuclei become more leaky, indicating that the older the organism from which the cell originates, the more molecules that are typically contained in the nucleus are likely to be present throughout the cell.

The breakdown of the nuclear barrier was measured using a fluorescent marker to establish the age of the cell.

Psychiatry instructor at Yale’s Department of Psychiatry Dr. Zachary Harvanek, who has conducted research on how aging affects epigenetics but was not involved in this study, stated in an interview:

“I believe the technique for promptly testing these medications in cell culture is the largest advancement in this paper. In terms of discovering new medicines or pharmaceuticals that would be helpful, I believe it could be a very significant development.”

Rewinding time by three years is allegedly possible.

The authors of the latest study subjected skin cells to a mixture of chemicals that had previously been proven to have an impact on the transcription of genes related to aging. One of the substances was valproic acid, which is used to treat epilepsy as well as other neurological and mental disorders.

They assert that their findings show that, contrary to what has previously only been shown with more than a year of regenerative treatment in people in published trials, the age of cells exposed to the chemical cocktails was reversed by 3 years in just 4 days.

Nevertheless, these tests were conducted in a lab rather than on live subjects. These cells were from a progeria patient, a 94-year-old donor, and two donors who were 22 and older. The paper omitted information about the subjects’ sex and ancestry, which might have an impact on the results.

Can humanity benefit from these discoveries?

In an email, Dr. Xiaojing Yang, the director of the Yang Laboratory at the University of Illinois at Chicago, who was not involved in the study but co-authored one with Prof. Sinclair earlier this year, stated: “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,” the researcher said. That being said, it’s crucial to keep in mind that it takes time and uncertainty to go from promising in vitro results to viable therapy in people.

Thus, even while this finding represents a fascinating development in the study of ageing, it is only one component of a challenging jigsaw. Before these findings can be applied to real-world anti-aging therapies, more study and validation, particularly in whole organisms, is required, according to Dr. Yang.

In agreement with this statement, Dr. Harvanek continued, “I think the fact that this particular cocktail seems to reverse aging in cell culture is a very preliminary finding. There is now, in my opinion, no proof that this will make humans or other animals age more slowly.”

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

REFERENCES:

• https://www.medicalnewstoday.com/articles/have-scientists-finally-found-the-way-to-the-fountain-of-youth
• https://www.dailymail.co.uk/sciencetech/article-3345359/Have-scientists-fountain-youth-Researchers-pinpoint-gene-say-boost-lifespan-25-cent.html
• https://www.technologyreview.com/2019/08/08/65461/scientist-fountain-of-youth-epigenome/

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