Tag Archive for: proteome

Eat Less, Eat Better, Move More—for Life

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In Tuesday’s Memo, Dr. Donal O’Shea suggested that there’s compelling evidence that eating less and moving more won’t result in permanent weight loss because the set point theory is just too strong and will defeat the effort of 90% of the people. However, he didn’t provide any evidence that’s true. I’ll give him the benefit of the doubt, because every study done on diets shows that people do gain back some or all of the weight they lost. He attributes that to the complexity of obesity.

The Complexity of Obesity

Take a good look at the graphic used in the heading. What you can’t read are the 198 determinants (all those gray lines) that contribute to obesity. He narrows them down to just seven categories, five of which are not under the control of people once they are fat. In case it’s difficult to read, here is the list.

  • Societal influences
  • Food production
  • Activity environment
  • Biology
  • Individual psychology
  • Food consumption
  • Individual activity

He also gives a compelling argument that the immune system, working in conjunction with fat cells, causes inflammation in a variety of ways which prevents people from losing weight.

The problem that I have is two-fold. First, it seems the last three are under the control of the individual: eating, moving, and deciding to do so. The exterior forces are what they are, but biology can change. Aging is the perfect example of that.

As for immunity, here’s the real question about the immune system: is it cause or effect? The increase in inflammation is remarkably similar to the increase in cortisol found in people who are obese. Is it the cause of obesity or is it the result of being obese? It makes a difference.

Why Medication Won’t Be the Permanent Solution

Before I get into this, I think that medications may play a role in the solution for some, maybe even most severely overweight people. But they will not be a permanent solution, and the reason may be found in the proteome. You may remember that those are the proteins coded for in our DNA; they range from hormones such as insulin to catalysts for other chemical reactions. There are about 5,000 proteins that are the most researched, but with about 20,000 genes, there may be at least 15,000 more genes that are not researched. That doesn’t count the post-translational modifications, modifications made to the protein as it’s being made; the total could get into the millions.

It’s unrealistic to think that a combination of three, five, or even ten receptor agonists will solve obesity and not cause issues elsewhere in the body by interfering with the production of other necessary proteins. I’m not suggesting that temporary use to get the bulk of weight off an individual won’t be a good way to start, but it’s not a permanent solution as I see it, even if you can afford to take it the rest of your life.

The Bottom Line

The issue with O’Shea’s approach is that it comes from a strictly medical perspective. A nutritional solution isn’t considered and somewhere along the line, just like with gastric bypass, people will exceed their desired caloric intake and regain weight. Why? Because they haven’t learned anything.

Remember, in those seven categories he cited, food consumption and activity levels are under the control of the individual. That means both the quantity and the type of food as well as the amount of activity are under the control of the individual. I’ll say it again: it was, it is, and it will always be about the calories—how much you take in versus how much you use. Take in more than you use, and you gain weight. It’s that simple.

Obesity is complex because our bodies are complicated, but this is still my recommendation: eat better, eat less, and move more. If I were to add two more words that I’ve implied but haven’t stated, they would be “for life” because the only way to hold on to your progress is to keep working on your lifestyle.

What are you prepared to do today?

        Dr. Chet

References:
1. SETU. Understanding Obesity: Rethinking Diagnosis & Treatment. 2024.
2. Nat Chem Biol. 2018 Feb 14; 14(3): 206–214.

Aging with a Vengeance and Your Proteome

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This year’s Super Bowl Webinar focused on aging with a vengeance—becoming the best version of yourself, no matter your age. The study we just reviewed on the proteome suggests that the people were healthier who were biochemically younger than their actual age. Here are the actions I believe can help at the three critical phases of aging that were identified in proteome study. As I find out more, I’ll be more specific.

31 to 37

If you have weight to lose, now is the time to lose it. Take it from me and my decades of experience with weight loss programs: it becomes more difficult the older you get. Find a way to eat that will maintain a reduced body weight and stick with it.

Reduce your protein intake. That may seem a little odd, but this is a time to focus on vegetables, fruit, whole grains, and quality oils.

Focus on your cardiovascular system by doing aerobic exercise on a regular basis. Use interval training to make the most of your time, and when you’re fit enough, you can add high-intensity interval training (HIIT) to your routine.

57 to 63

The kind of 80- to 85-year-old you’re going to be is dependent on what you do now. If you haven’t achieved a normal body weight, that’s a high priority just as it was in the prior age group. I know how difficult this is because it’s eluded me throughout my life; I lost a lot of weight and kept it off for years, but I’d still like to weigh less.

Increase protein intake to 1–1.5 grams per kilogram body weight per day.

Supplement your diet with essential amino acids. While the amounts are still not absolutely clear from the research, 10–20 grams per day is a good goal.

If you’re not already doing so, add weight training to your exercise routine. Start with using your own body weight, then add exercise tubes or light weights, and then use machines or free weights. Now is the time to retain or even increase your muscle mass.

75 and Older

If you haven’t achieved a normal body weight, there’s still time. My wonderful mother-in-law lost a significant amount of weight at this age, and she was an overweight diabetic in a wheelchair.

Increase protein intake to 1.5–2 grams per kilogram body weight per day. It’s difficult because appetite decreases and protein makes us feel full. It will help reduce the muscle loss that’s happening.

Supplement your diet with essential amino acids; the amounts are still between 10–20 grams per day.

Add weight training to your exercise routine. It will help you to retain or even increase your muscle mass. Stay within any orthopedic or other limitations, and get some help if you need to, but do it. Your primary caregiver will probably be glad to refer you to a physical therapist who can get you started safely.

The Bottom Line

For all that’s been written about healthy aging, we still don’t know very much. Healthy aging begins the day we are born, but we realize that only when it dawns on us that we’re aging. No matter your age, no matter your current state of health, it can be better. You can learn more in the replay of this year’s Super Bowl Webinar, but it will be available for only a little while longer.

The simple things I’ve talked about in this Memo are a beginning. When I know more, so will you. Inevitably, it comes back to a single question:

What are you prepared to do today?

        Dr. Chet

Reference: Nature Medicine. 2019. https://doi.org/10.1038/s41591-019-0673-2

Proteome: Predicting Your Age

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Have you ever taken a test or questionnaire that predicts your health age? What they’re really predicting is your longevity based on lifestyle factors and where your health stands today. What if you could be more precise in actually calculating your health age? That’s what researchers did based on the results of the proteome study I talked about last week.

The researchers identified 373 proteins that could be used to predict someone’s age within about three years. They used proteome data from other studies to test the predictive capability. When the test predicted people were younger than they actually were, those people did better on cognitive and physical tests. That means the proteome was revealing a pattern of proteins associated with someone who was younger.

Don’t run out to get this test; it isn’t available—yet. Scientists are working to narrow the proteins included in the age-predictive equation; there’s a lot of work to be done before it can have any clinical significance.

Does that mean there’s nothing we can do now, test or no test? I think we have some options, and I’ll tell you about that Saturday.

What are you prepared to do today?

        Dr. Chet

Reference: Nature Medicine. 2019. https://doi.org/10.1038/s41591-019-0673-2

The Proteome: A Cross-Sectional Study

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Every study begins with a question. A single question often leads to more questions, which leads to questions about whether the outcome can be measured, and on and on. In this case, the question was related to changes in the blood proteome over a lifetime: Is the proteome stable? Is it a series of continuous reduction or expression in some key proteins, or are there identifiable changes that occur at different points in a lifetime?

The best way to know that is to obtain serial blood draws from a group of individuals every year (or two years or five years) to track changes in the blood proteome, the entire collection of proteins in our blood cells. We live too long to make that practical. The next best thing is to select a large group of people of all ages, get blood samples from each along with other demographic and lifestyle measures, and compare the differences over the entire age-span. That’s a cross-sectional study.

Here’s what a large group of researchers choose to do. They recruited 4,263 people from 18 to 95 years old. Getting blood samples and other data from the subjects, they measured 2,925 blood proteins. Stop and think about that: they looked at over 12 million data points. The technology to measure each protein is incredible in and of itself; now add to that the sheer volume of number crunching that it takes to analyze that much data. Without high-speed supercomputers, it wouldn’t be possible in a reasonable amount of time.

The researchers found that over the years 1,329 proteins varied at different ages of the subjects; the ages where there was more variability than at other times were about 35, 60, and 78 years old. What does that mean? The first step in finding out would be to identify all the proteins and find out what they do. If some form of lifestyle change could impact aging, that would be necessary to know.

But that isn’t all they did with the data: scientists love predictive algorithms. We’ll take a look at what they discovered on Tuesday.

What are you prepared to do today?

        Dr. Chet

Reference: Nature Medicine. 2019. https://doi.org/10.1038/s41591-019-0673-2

What Is the Proteome?

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In the week we took off, I spent my time researching a couple of fascinating studies. We all have different ideas of what’s fun, don’t we? For me, getting to research topics in depth is a refreshing opportunity to learn something new. I’m going to share part of what I learned in the next several memos and it’s all about the proteome.

Obvious question: what is the proteome? A proteome is the complete set of proteins expressed by an organism—same idea as the microbiome, but with proteins instead of microbes. That includes obvious proteins such as muscle, hormones such as insulin, or many of the thousands of enzymes and other proteins the body makes. Those proteins may be produced only during specific circumstances and in response to events within and outside the body. The proteins can be systemic or they can occur in individual tissues and cells.

More than what, why is the proteome important? Research has demonstrated that there’s variability in the proteome at specific times during life. The idea is to identify which proteins change and which ones are associated with a healthier life. That’s the first step and I’ll cover a study that did just that on Saturday.

Tomorrow is the monthly Insider conference call. Check out the membership and if you become an Insider before 8 p.m. Wednesday, you can take part.

What are you prepared to do today?

        Dr. Chet

Reference: Aging Cell. 2018;17:e12799. https://doi.org/10.1111/acel.12799