The Life Extension Advocacy Foundation volunteers have a stack of interview materials piled up from the recent Undoing Aging conference, I'll wager. Today they published a lengthy interview with Steve Horvath, originator of one of the epigenetic clocks that assess age based on patterns of DNA methylation. I have to say that it is a pleasure to see so many researchers now willing to talk openly about therapies for aging and their hopes for the future of the field. For so very many years that just didn't happen; no researcher was willing to speak in public on the topic of treating aging as a medical condition and extending healthy life.
When I first become interested in this field, the research and funding institutions that dominated the study of aging were quite hostile towards anyone who wanted to intervene in the aging process and thereby produce longer lives in patients. Thankfully, times have certainly changed since then, and for that we can thank the hard-working community of advocates, scientists, and philanthropists who have since the turn of the century built funding and support for rejuvenation biotechnology, and for the transformation of medical science through the treatment of aging.
The Horvath epigenetic clock has a commercial implementation, myDNAage, produced by Zymo Research. The folk there claim it to be quite stable over time and circumstances in its assessment, with a margin of error of 1.7 years. As noted in the interview, it is one thing to have a metric that maps to age quite well, and shows some signs of reflecting biological age versus chronological age, but it is quite another to know what it is actually measuring. These changes in DNA methylation are some reflection of the growing damage and dysfunction of aging, but are they a very selective reflection? What if it is found that when a human undergoes a senolytic therapy to remove senescent cells, one of the root causes of aging, that before and after measures of epigenetic age are the same? That would be an interesting outcome, and we're about to find out, but what could we learn from it? This result seems unlikely given that cellular senescence appears to contribute to many aspects of age-related decline, but it isn't impossible. Researchers really don't know whether the epigenetic clock reflects one or many of the underlying aspects of aging.
Science and medicine are often a process of starting at the ends and meeting in the middle. A list of the root causes of aging exist, and measures of the state of aging exist, but there is not good map to link those two. Aging progresses in a very complex way, even though it is caused by comparatively simple and easily understood processes, because our biology is very complex. The fastest way to build rejuvenation therapies and metrics to measure the results of rejuvenation therapies is to start on both lines of research and development at the same time, and compare the results against one another. Iteration on this theme will find the path ahead, and allow unhelpful approaches to be discarded earlier rather than later.
Why is the epigenetic clock more accurate than measuring telomere length?
Yes, it is far more accurate, there is no comparison. Why is a good question. In my opinion, it shows that epigenetic changes are far more important for aging than telomere maintenance. People have studied telomeres for many years, including me, but telomere shortening alone does not explain aging. You may know that mice have perfect telomeres, but they only live three years.
It's known that cells in our body are renewed at different speeds; why does your clock measure the age of the tissue or whole organ and not the age of specific cells?
Actually, it does measure the age of specific cells. You can have liver cells, and the epigenetic clock works beautifully. It also works very well for neurons and glial cells. Even in blood, you can have sorted blood, for example T cells or B cells, and the clock works on those cells.
Does your clock represent aging?
This is a good question with two answers. One way to ask this question is to ask if methylation changes cause aging. And we honestly don't know; there is no data. The other question to ask is if the epigenetic clock is the indicator of a biochemical process that plays a role in aging. Which I think it is; it is a biomarker of a process. There is no question that this process that underlies the clock, that if you target this process, you slow aging; this, we know.
What is going to happen if we influence this methylation process?
With the methylation process, we don't know. Imagine that you have a clock; there is the clock face with the dials, and then there is the clockwork. The discussion with the epigenetic clock is whether methylation is part of the dial or is it part of the clockwork. There is no doubt that it is part of the dial, and if you interfere with the clockwork, there is no question you that rejuvenate people. But it could be that the clockwork might not be the same as methylation; we are not sure. With a clock face, you can just take the hands and move them, but it may do nothing to actual time. Behind the clock, there is the clockwork, and we don't completely understand the clockwork. A lot of people are asking about it, but we just don't know yet.
Can we slow down aging now?
I want to tell you that I am very optimistic and that we will have treatments against aging in a few years. I could be wrong, and I want to be cautious, but I want to tell you that I am very optimistic because we already have encouraging results. We already have treatments that have a huge effect, like the Yamanaka factors in mice, but also in human cells. If you use Yamanaka factors on human cells, it completely reverses their age. The problem is how to make them safe.
My hope is that maybe even our generation will benefit from it; certainly, my daughter should benefit from it. I would be absolutely shocked if the next generation does not live twenty years longer. On that level, I am very optimistic. If you ask me right now what you should do, I can only tell you boring things; immediately stop smoking, avoid obesity, avoid diabetes; if you are a diabetic, manage it; avoid high blood pressure, and if you have it, take action. It is boring, but all my studies show that this is the best thing we can do now.
What are the main challenges in your research in aging?
Scientific challenges, honestly I don't have them. Because there is so much work to do and I have a good plan, it is not a problem. Financially, there is a challenge; research is expensive, especially human trials. I have a very exciting collaboration with a company which has an anti-aging treatment, and to test it will cost three million dollars. So, as you can imagine, money is the challenge.