🧬🛍 13 - Exclusive Q&A Dr. Charles Brenner: a different voice in longevity
Resveratol good for longevity?, Microbiome Report
Hello again 👋
This is Curation for Longevity 🧬🛍 by Laura Minquini. I am the founder of MYKIGAI - a discovery and recommendation platform for longevity.
Exclusive Q&A with Dr. Charles Brenner
No curation of longevity would be complete without including contrarian voices on the current state of the science.
Enter Dr. Charles Brenner, who is not spending a lot of time becoming a household name but is well known in scientific circles. He is an expert in NAD+ metabolism and it is his research breakthrough on NR (nicotinamide riboside) that is responsible for one of the most successful, trusted, and well-known supplements in the longevity/biohacking world: Tru Niagen. Our Geroscientist, Girish Harinath’s father’s health was greatly improved by it.
About Dr. Charles Brenner:
Dr. Charles Brenner is the Alfred E Mann Family Foundation Chair in Diabetes and Cancer Metabolism at City of Hope National Medical Center. In 2004, Brenner, then a faculty member at Dartmouth College, discovered nicotinamide riboside (NR) to be a vital precursor of nicotinamide adenine dinucleotide (NAD+), which is made available by nicotinamide riboside kinases (Nrks) that are conserved between yeast and humans. In 2007, Dr. Brenner’s lab discovered a second pathway by which NR is converted to NAD+ and showed that NR can extend the lifespan of yeast cells by virtue of elevating NAD+ levels and increasing the activity of the NAD+-dependent Sir2 enzyme.
I have been paying attention to his takes and after this tweet below, and my comment on it, we engaged in conversation.
I pointed out to him that the boogie men in this space are not his colleagues in the world of science, but the plethora of self-appointed experts and MLM companies.
We live in a world where even some of my friends believe more in MLM than what we are doing at MYKIGAI. These companies use such incredible psychological tools, that everyone I know who is engaged in them repeats the same lingo like: “you get out what you put in”. More recently, these companies have added to their communication terms like “data”, “studies”, "natural", and “clean” to add an aura of credibility to their sales pitch. Compare this to my mention of “science” and “biotech” to anyone who equates "holistic" with "natural", and they think I am talking about The Simpson’s radioactive green🧪.
Holistic and science are not mutually exclusive. I lived in Hong Kong for a year and love everything eastern medicine has to offer. I have even seen the benefits of all these holistic approaches to my mother’s health.
And I don’t want to make enemies with my chakras and crystal-loving friends, for full disclosure, I once had a Feng Shui master, I like guessing people’s astrological signs, and love healing sounds of the east with a reiki massage. As Brenner says, “You do you”, and if what makes you feel good is burning lavender oil and having a crystal collection to relax you, then half the battle is won.
The placebo effect is powerful, or as one Victorian-era writer wrote, it is “As a man thinketh”. Watch this episode of the Huberman Lab on how your mindset affects your food intake, he touches on all the different diets, including IF on this clip.
However, in a world where endocrine disruptors are a thing and microplastics are in our bloodstream, it won't be the castor oil that will solve the diseases that come from them, we will need science and biotech. Think of it, organ transplants, which are accepted tools of life extension were brought to us by the wonders of research and scientific progress.
With this said, and being called a cheerleader for longevity & science, I do want to share Dr. Brenner's opinions. For one, because I am an equal opportunity provider, and also because I understand enough to know science is evolving. While studies on mice and worms are a great start, we can't promote something without acknowledging its limitations.
By declaring things conclusive and then later studies are published debunking these “conclusive” studies - we sow distrust from the general public - and right now the companies with great sales techniques and messages - not necessarily the science - are winning the battle of health communication.
Q&A with Dr. Brenner
Dr. Brenner, you are an outspoken person in the current state of longevity science and what's been promoted. Lately you have had a lot to say on Intermittent Fasting (IF), and we ourselves published a guideline to the practice recently.
Q: As someone who studies metabolism closely, please tell us why you reference orthorexia a lot and why you think it is so dangerous to promote something one could equate to a dietary fad?
A: Thanks, Laura. There is a problem with nutrition and lifestyle influencers who have very specific recommendations for everyone. For example, everyone should eat keto, everyone should eat only plants, everyone should eat no plants, everyone should do intermittent fasting, everyone should do some particular lifestyle intervention. None of these specific recommendations will be sustainable for large fractions of the population. Many people are susceptible to believe that particular food groups are toxic when, in fact, there are high functioning people who eat no meat, some meat, keto, lots of carbohydrates, 3 meals a day plus snacks, 3 meals, 2 meals, 1 meal, etc, etc, etc. When people become obsessively attached to particular eating practices, their relationship with food is degraded and they can develop orthorexia nervosa, a distinctly unhealthy obsession with something termed “clean eating.” The nutrition influencers that most greatly drive orthorexia are generally not evidence-based in vilifying particular foods or eating practices and do more harm than good.
Q: From your knowledge of the latest published research, what do you think it is important the general public understands when it comes to:
A: On Intermittent Fasting
There’s a big difference between mice and people. A given length of time fasting has a much greater effect on mice than on human beings. Though it is frequently claimed as an aid to weight loss, you have to realize that establishing the intention to lose weight has a measurable and beneficial effect on weight in the short term. When Dr. Ethan Weiss did a randomized controlled trial of 16:8 IF against a control group who also intended to lose weight but had no such restriction, there was no weight loss or cardiometabolic advantage to IF. The study is here: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771095
If someone does IF to improve their focus or whatever and it works for them, I’m happy for them. Personally, I’m a breakfast guy—my first meal is around 6 am and my last around 6 or 7 pm. That’s what suits my focus, intellectual and physical activity and my social life. I certainly would not advocate another person’s meal timing. Whatever they are doing has to work for them. As I say on twitter, you do you.
A: On Metabolism
We could go 24 hours on this one but let’s just tell your readers that fasting doesn’t boost your metabolism, it depresses it, metabolism doesn’t generally decline until we turn 60, and the energy balance model does explain human weight management and the obesity epidemic. We can return to these or other issues of metabolism in the future.
A: On Ketones
Ketones are what the liver produces when our blood sugar is low. The brain can use them as an alternative fuel source once liver glycogen is exhausted and when gluconeogenesis can’t keep up. Note, Dr. Brenner asked me here what I wanted to know more specifically but I missed his question so we are going to have a follow up to this!
Dr Brenner, people know what they need to do to stay healthy - but knowing and practicing are different. I personally prefer people to look at scientists than crystal healers to improve their health.
Q: I consider you a scientist working in longevity, is that something you are comfortable with or not?
A: I’m a metabolism scientist who is very interested in longevity. I don’t like the term anti-aging and I’m critical of people who claim that they understand aging, have identified monogenic longevity genes that they can activate, or claim to have reversed aging. None of those things are scientifically defensible.
Q: What do you recommend as a solution to better communication of science that also encourages people to trust it and get on a healthy routine?
People need to be able to identify sources of misinformation. Anyone who claims to have reversed their own age or activated longevity genes is a source of misinformation. People who conflate fertilization of oocytes from older women with age reversal are deeply misinformed—all oocytes are kept at the same stage of development throughout a woman’s lifetime. People who think that Yamanaka factors are not oncogenic and teratogenic are misinformed.
Q: Wait, what? I know that Yamanaka factors are used to induce pluripotency and people are trying to use them to rejuvenate tissues.
Correct. The Yamanaka factors are known oncogenes. They play roles in development and proliferation but are generally turned off in tissues because the cells are already differentiated. When people induce pluripotency, they also can generate cancers or teratomas, which are clusters of cells that are very much misbehaving. If the idea is to take cells from an older person and induce pluripotency or partially deprogram it, there’s no doubt this can be done—one is discarding the cells that are misbehaving due to oncogenic and teratogenic activities of the Yamanaka factors. But the idea that we’d treat a tissue in a living person with Yamanaka factors and be able to control the outcome is quite farfetched. There is an experiment in which a research group claimed to do this to a tissue in mice but the study was not blinded and has not been replicated by any other group. In fact, all leading groups working on Yamanaka factors acknowledge the oncogenic and teratogenic potential of these treatments.
Dr. Brenner is currently making the rounds with a new lecture that debunks the mythology of sirtuins as animal longevity genes. He is very excited about the potential for nicotinamide riboside as a booster of innate immunity to viruses and as a molecule that can help build resiliency to multiple conditions of metabolic stress. People can follow his research at: https://brennerlab.net
Everyone is welcome to ask questions on twitter @charlesmbrenner
Is Resveratrol good for longevity? 🍇🧬
We got lucky as we were getting this edition ready as a video on the history of Resveratrol research, and if it is actually good for longevity, was published by Dr. Brad Stanfield. It helps to contextualize Dr. Brenner’s interview.
Biggest takeaways:
Resveratrol blunts the effects of exercise
It does not activate Sirtuin 1 (SIRT1) “longevity gene”
We don’t have robust human data to show benefits
There is no lifespan extension
MICROBIOME REPORT: Optimizing the Gut-Brain-Axis for brain health 🧠
Few people truly realize the profound influence gut health has on their brain aging and mental health. Yet the scientific literature is peppered with evidence illustrating how pathological changes to our gut microbiome can drive the progression of neurodegenerative diseases like Alzheimer’s disease.
Beyond that, the behavior of our gut microbiome plays a huge role in determining our quality of life on a daily, moment-to-moment basis. This is because our gut is in constant communication with our brain, engaged in a bi-directional conversation that influences our emotional health, cognitive health, and behaviors. Collectively, this interaction is called the “gut-brain axis”.
In fact, our gut microbiome directly produces or modulates over 50% of the factors coursing through our circulatory system at any given moment. This includes critical neurochemicals and hormones such as serotonin, dopamine, cortisol, and estrogen. So it is no surprise that gut issues (i.e. IBS, IBD, celiac disease, etc) tend to go hand in hand with mental and social disorders such as depression, anxiety, and autism.
Leading-edge scientific research is revealing that there is so much we can do to heal our guts and optimize the ongoing cross-talk between our gut and brain, much of which is what we call low-tech longevity.
All the checklists and protocols within our Longevity Toolkits recognize the integrated nature of our body. An effective healthy longevity strategy has to reach beyond addressing just one layer of physiology and cater to as many aspects of health as possible. In this series we will address microbiome health as follows:
Part 1 Glossary & Basic Microbiome Checklist for Brain Health
Part 2 Oral Microbiome & the Alzheimer’s connection
Part 3 Vaginal Microbiome and Hormonal Health
Part 4 Complete Microbiome Checklist
Our Longevity ToolKit is where we store our educational libraries of health checklists and easy-to-implement recommendations for longevity. Researched and distilled by Girish Harinath, Geroscientist at MYKIGAI
ANNOUNCEMENTS 📣
We extended our offer to test your gut microbiome with VIOME
Upcoming Longevity Drop🧬💧 and exclusive offers for our members this month:
BRISTLE HEALTH - A simple saliva test to test oral microbiome
JUNOBIO - Testing vaginal microbiome for women’s health
It’s all about the microbiome this month…you might have noticed!
This Week LONGEVITY TOOLKIT: Glossary & Microbiome Checklist for Brain Health - Part 1 👉🏼
Keep reading with a 7-day free trial
Subscribe to Longevity Lifestyle with MYKIGAI to keep reading this post and get 7 days of free access to the full post archives.