The Non-linear Path of Aging: A Conversation with Professor Michael Snyder on Biomolecular Shifts and Health

As we mark Healthy Aging Month this September, we are delighted to present an insightful conversation with Professor Michael Snyder, a distinguished leader in genetics and Director at the Center for Genomics and Personalized Medicine at Stanford Medicine. His team's recent publication in Nature Aging on the nonlinear progression of aging has sparked significant interest in the scientific community, shedding new light on the complex biological processes that define our later years. This discussion highlights the latest advancements in aging research and explores their potential implications in health and longevity.

In your recent paper on Nature Aging, your team highlights that aging is a nonlinear process with massive biomolecule shifts occurring in an individual’s 40s and 60s. Can you elaborate a little bit more on your findings?

Michael Snyder: What we're really doing is pulling back the curtain and looking in more detail at exactly what's going on with the aging process as we track people. We've been measuring people very deeply. We make literally over 100,000 measurements on people from their blood, microbiome, and other samples. We follow them over time. What most people expected is that people age linearly, meaning at a constant, slow, gradual fashion. But what we found, by making all these measurements and looking in detail, is that that's not the case. There are some changes that occur gradually over time. But we discovered there are two major times when you see a lot of changes. One is when people are in their 40s and another is at their 60s.

The one in the 60s was not a surprise. Most of us know that when people hit their 60s, they start seeing wrinkled skin and they move a lot slower. We also know that their immune system declines. That’s why it's very important to get the influenza vaccine as you hit your 60s. But the one in the 40s was a surprise. We knew there would be changes again throughout your life, but I don't think we expected a big burst necessarily. Although I think in hindsight, some people might say, “well, that's when people start pulling muscles and having problems when they exercise, their metabolism slows,” but we definitely see it at the biochemistry level.

The implications of these findings seem quite profound. How do you see this new understanding of aging impacting the way we approach health and wellness, especially as we navigate through these critical decades of life?

Michael Snyder: There are a lot of direct applications of this work. For example, one of the big changes we see as people hit their 40s is they see changes in their lipid profiles. We think that's why their cholesterol is going up, their fat deposition changes and so on.

The other big changes we see at both periods are changes in muscle and skin. Changes in muscle are a big deal. As you hit your 60s, if you lose muscle mass, you get something called sarcopenia where you move very slowly and have trouble moving at all. And that leads to a very serious health issue. It turns out that exercise avoids that and can keep your muscles in good shape, especially resistance training and weightlifting. The changes we see are actually in some proteins that are involved in maintaining muscle and tissue integrity. So exercise will keep those proteins in good shape and keep your tissues in good shape.

As you hit your 60s, we see changes in people's kidney function and immune systems, so you can drink more water or eat more anti-inflammatories. So there are very direct actions you can take to improve your health.

Do you see those shifts potentially serving as biomarkers for diseases related to aging?

Michael Snyder: That’s a great question, and the answer is yes. When we're doing these in-depth profiles, we can see exactly what molecules are changing. For example, some of the skin and muscle markers are extracellular matrix proteins, like collagen. For cardiovascular disease we see several markers. Some of them are the lipids like HDL and LDL, but there are other markers, like the things involved in fibrosis, which is a big deal during aging. By tracking a lot of molecules, you actually get a much clearer picture of people's health.

We think it is very important to get a much more comprehensive picture of health rather than what we do today. Today, we actually don't make many measurements. We typically measure maybe 15 things in a doctor's office visit, and don’t do it very often. But we think with these new in-depth measurement methods, like we do with wearables and micro sampling technology, we can track people in a lot more detail than has been done historically. That's going to be important for keeping them healthy.

Any implications for clinical trial designs?

Michael Snyder: In terms of the therapeutics per se, we're not there yet for new targets to hit. But it could tell us when to start taking some of those drugs, like statins, before you get these problems or when you first start seeing them. So it could guide us when to start some of these prophylactic treatments. I think that will be important. If that is the case, we could easily redesign our clinical trials. We tend to do clinical trials around single endpoints - are you improving this or are you improving that. But we think by our tracking method, we can set up new endpoints and follow them in real time so that you could actually get an early indication of what's going on. You might track that early on and see what kinds of shifts are really occurring and then intervene accordingly.

How do you envision the integration of AI and advanced data analytics in tailoring healthcare to individual health needs?

Michael Snyder: Absolutely. With A.I., we can bring in our information in a very personalized fashion and be able to make very specific recommendations, not only around lifestyle, but also around the medicines. We can keep track of these medicines and understand better what their interactions are going to be with other drugs you are taking as well as with your lifestyle. In the end, we can collect a lot of different data around people, and make very precise recommendations. We're not there yet. We can do some of this now, but we can take this even further in the future.

That's a really exciting future we can all look forward to. Before we wrap up, is there anything else you’d like to add?

Michael Snyder: People do a lot of health tracking in general, which we think is very important. And if you can do it remotely with wearables, you can do it continuously, which is powerful. Now we do a lot with something called micro sampling. We can profile thousands of metabolites in the lab from little drops of blood. I think that is going to be the future of medicine - do a lot of health tracking at home at your convenience, and we need to do it much more frequently to detect the early signs of potential issues.

Again, the goal here is really to have people live long, healthy lives so that you're not spending the last decade of your life unhealthy. We want people to live healthy lives all the way to the point where they die. That's our goal. And I would argue most are not doing it. Most countries practice sick care. They really tend to treat people when they're sick as opposed to keeping them healthy. And that's what we want to change.

Thank you, Professor Snyder. It has been an enlightening discussion. Thank you for your continued contributions to the field and for taking the time to share your insights with us today.

Michael Snyder: My pleasure.