Fighting Zika and inhibiting COVID-19, the natural antiviral compound 25HC has transformed into an anti-aging nova

Editor's Note

This article was compiled by the Time School Institute from Lifespan's interview with Simon Melov.

Dr. Simon Melov is a senior researcher at the Buck Institute for Aging, where he leads a lab specializing in senescence and marker recognition at the cellular level. Recently, Melov's research team discovered a new anti-aging molecule, 25HC, which can accurately locate and eliminate senescent cells by identifying target proteins to achieve life extension. His research also pioneered the application of cutting-edge technologies such as single-cell genomics, leading future anti-aging research.

In this interview, Dr. Melov answers questions about what is single-cell gene technology, the role and prospects of the 25HC molecule, and target proteins and markers of aging.

Original link:

https://www.lifespan.io/news/dr-simon-melov-on-single-cell-genomics/

Q: By employing cutting-edge technologies such as single-cell sequencing, your team has discovered a completely new anti-aging substance. Can you tell us more about this technology?

A: For a long time, researchers had a hard time determining the causes and accelerated aging, and the problem was in the research methods. Past aging studies have been based on a group of cells rather than a single cell, and only the average aging signal of this group of cells has been derived. But in fact, the rate of aging is different for each cell, and we ignore the important changes and connotations contained in a single cell.

Fortunately, in the past decade, aging research methods are undergoing a slow change, and single-cell gene technology has begun to rise, helping anti-aging research breakthroughs. At present, a number of research institutions in the United States are working together to carry out the "SenNet" project to try to map cellular aging based on single-cell gene technology. The Buck Institute is also involved, and we focus on mapping the aging of cells in muscle, ovarian, and breast tissue.

With the help of single-cell gene technology, we found that:

Single-cell biology tools can be used to identify potential targets that mediate aging, laying the groundwork for the subsequent development of new drugs for these targets to delay cellular senescence.

Preliminary studies have found that the CRYAB protein may be a potential target protein.

25-hydroxycholesterol (25HC) molecules have demonstrated the ability to kill aging cells in a variety of tissues in multiple species, or may become potential anti-aging drugs.

Q: Can you elaborate on the target protein CRYAB mentioned in your study?

A: CRYAB is a heat shock protein that regulates apoptosis. A study more than a decade ago noted that as we age, the insoluble CRYAB protein accumulates in large quantities in human skeletal muscle. Based on this, we are currently exploring whether the aggregation of target proteins in many ways destroys protein homeostasis and allows cellular aging to take advantage.

Our research focuses on skeletal muscle cells, which are long strips, also known as skeletal muscle fibers. Unlike ordinary cells, which have only one nucleus, skeletal muscle cells can contain hundreds or thousands of nuclei, arranged and distributed on the surface of the cell to form syncytial bodies. Such a special structure contributes to the movement of the body, but it also adds difficulty to study apoptosis in skeletal muscle.

We found that all types of cells respond to the 25HC molecule when they age, a natural immune antiviral small molecule compound that also inhibits COVID-19 infection. 25HC preferentially kills senescent cells, while CRYAB is a target for senescent cells, pointing the way to the 25HC molecule, and we are currently studying its mechanism of action.

Q: What are your thoughts on clinical trials of 25HC molecules?

A: The current discussion is more focused on the role of 25HC against COVID-19, not its anti-aging effects, but the mechanism of action of endogenous 25HC molecules to kill senescent cells is still fascinating. As for clinical trials, it must be very difficult, but that doesn't mean we can't do anything about it, and I think small trials can be the first step.

Q: What do you think of the development prospects of senescent cell scavenging drugs (senolytics)? Will their development be frustrated by the lack of effective enough or severe side effects?

A: It's too early to say, we haven't seen the successful application of aging biology, and there are no rationally designed senescent cell scavenging drugs approved for marketing. It was true that there were hot drug candidates who were only one foot away from success, but in the end they were defeated due to various factors. Personally, suppressing the TOR signaling pathway or reversing epigenetic changes promises the success of anti-aging drugs.

Q: Your paper mentions the aging markers 15-deoxy-δ-12, 14-prostaglandin J2, how does it work and what are the criteria for measurement?

A: Early last year, Judy Campisi and Chris Wiley discovered this marker, an oxidized lipid, that we applied to study aging and the use of senolytics to treat older animals. This marker molecule is produced only in senescent cells, and when senescent cells are apoptosis and dissolved, the marker can be detected in plasma and urine.

The number of this marker molecule in older animals is significantly higher than in younger animals, because older animals have more senescent cells in them. After using senolytics, the number of markers rose further because senescent cells released the markers after they were killed. We're happy with this rise, which shows how senolytics are useful in removing senescent cells and delaying aging.

Counting cellular senescence in vivo is difficult, so this marker is very useful.

Q: Is lifestyle related to the accumulation or breakdown of senescent cells?

A: Lifestyle changes are currently the only viable anti-aging interventions, and the questions you asked are also the research direction of another important project of ours. The project has single-cell mapping of thousands of mice receiving different anti-aging interventions, and exercise and taking anti-aging drugs such as 25HC are also variables, and I may be able to answer your questions once the results are available.

Exercise has a profound effect on slowing down the decline of aging-related functions, which is naturally a topic of great interest to us. Sedentary and overeating will accelerate the aging of the body system, and maintaining exercise and eating a healthy diet is actually to get your body back on track.

Q: Do you think single-cell technology will be widely used in research and become an important scientific research tool?

A: Our lab has been studying aging through the lens of single-cell biology for more than a decade, and I believe that single-cell genomics has a deep potential in aging research and can bring great rewards.

Single-cell technology has its place in developmental biology, cancer treatment, and the treatment of other diseases, but I think that applying this technology to aging research can maximize its value and achieve major breakthroughs.

Of course, genomics is huge and complex, tissue aging is ever-changing, and if you want to understand the differences in gene expression in humans, adequate funding and strong computing power support are indispensable, which are all problems that cannot be ignored. But I believe that these problems will eventually be solved, and the development of single-cell technology is improving.

Q: Are you optimistic or pessimistic about the current field of aging research?

A: I'm objective, and as I said earlier, advances in technology have allowed us to do research at a single-cell level, filling the gap that was lost thirty or forty years ago. Now we can read thousands, hundreds of thousands, or even millions of cells at the single-cell level and transcribe spatially with the help of advanced instruments. This technique enables precise localization of capturing cells, transcriptome sequencing of individual cells, and quantification of gene expression. These technologies can help us break down barriers to scientific research and explore endless possibilities.

—— TIMEPIE ——

Here is a time school that only does the most hard-core continuation research, focusing on "longevity technology" science. Day and night to read the literature to write only to bring you the latest, most comprehensive cutting-edge anti-aging information, welcome to leave your views and doubts in the comment area; day more motivation comes from your attention and sharing, anti-aging road with you side by side!