Summary: (Video) Watch Dr. David Sinclair explain how sirtuin genes control cellular repair and how drugs and supplements that affect the sirtuins can slow the aging process. [Author: Brady Hartman. This article first appeared on the website LongevityFacts.com. Follow us on Reddit or Google+ ] Scroll down for video
Sirtuins are a family of genes, enzymes, and proteins, which affect multiple pathways that increase the lifespan and the overall health of organisms. Since enzymes are proteins and genes code for proteins, sirtuins are interchangeably referred to as enzymes, genes, and proteins.
Researchers have linked sirtuins to influencing a wide range of cellular processes such as cellular stress resistance, inflammation, transcription, aging, and apoptosis (cell death). For example, geroscientists have linked the sirtuin SIRT1 with apoptosis; cancers; promoting liver function and regeneration; delaying replicative senescence in primary fibroblasts; stem cell differentiation and cell fate determination; and neuroprotection against various neurodegenerative disorders, such as Parkinson’s and Alzheimer’s.
As well, researchers have linked sirtuins to energy efficiency and alertness during the low-calorie situations that occur during intermittent fasting and calorie restriction, although the relationship is controversial. Sirtuins can also control circadian clocks and affect the creation of new mitochondria.
David Sinclair on Sirtuins
Harvard Professor David A. Sinclair, Ph.D. is best known for his research on aging and lifespan extension. Honored by TIME magazine as one of the 100 “most influential people in the world” in 2014, Dr. Sinclair is Co-Director of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging at Harvard Medical School and a Professor at the University of New South Wales, Sydney.
In 1995, Sinclair received a Ph.D. in Molecular Genetics and went on to work Leonard Guarente at the Massachusetts Institute of Technology. Since then, Sinclair has received many awards and honors including the CSL Prize, Merck Prize, The Australian Commonwealth Prize, Thompson Prize, Bio-Innovator Award, Australian Medical Research Medal, Nathan Shock Award from the National Institutes of Health, Ellison Medical Foundation Junior and Senior Scholar Awards, Genzyme Outstanding Achievement in Biomedical Science Award, The Frontiers in Aging and Regeneration Award, Top 100 Australian Innovators.
In the following video, ‘David Sinclair – Slowing down Aging.’ Professor Sinclair explains the role of sirtuin genes in the aging process as well as the drugs that Sinclair is working on – compounds that slow down the aging process by affecting the sirtuins. For those short of time, a rough transcript organized by topic follows the video. Link: https://youtu.be/lA4DbN01q70
Rough Transcript of ‘David Sinclair – Slowing down Aging.’
[Author’s Note: This is not a word for word transcript of the Sinclair talk on sirtuins and aging. To improve readability, minor grammatical corrections have been made and section headers added .]
Introduction (David Sinclair)
“My research is based on the idea that we can find ways to slow down diseases of aging and maybe even aging itself. When I started doing this about 15 years ago, this was considered a crazy idea to find genes that actually control the aging process. But actually now we know there are genes in our bodies there are seven of them that we work on called sirtuins, and these genes we think controlled the body’s natural defenses against diseases and aging itself.“
David Sinclair on Sirtuins and Aging
“The overall theme of my lab’s research over at Harvard Medical School is to find ways to tap into our body’s natural defenses and turn on these genes [sirtuins] that exist in ourselves, but they typically don’t do a very good job. We’re trying to make medicines that will turn on these pathways, these very ancient pathways, and boost them in a way that will slow down diseases. When I say diseases that includes essentially all of the major diseases of western society of the developed world. So there’s cancer, Alzheimer’s, osteoporosis and heart disease.”
David Sinclair on Drugs That Affect Sirtuins
“What we’re finding in the lab by tweaking these sirtuin genes and even some of the drugs that we have in clinical trials – they’re able to slow down not just one of these diseases but actually slow down all of them and even reverse some of them. The future that I hope to see if this research comes to bear – I really think that it’ll happen in in our lifetimes – is that a patient could go to their doctor and let’s say they have high blood sugar they have type 2 diabetes. The doctor will say well we have this medicine its breakthrough medicine brand new on the market and it’ll bring down your blood sugar. You the patient says that’s great news. The doctor says well I have to warn you there are some side effects to this drug. Some of the side effects include you’ll be protected against cancer and heart disease and Alzheimer’s and osteoporosis and by the way your memory will improve.”
“Now that sounds like science fiction, but actually we do this all the time in the lab with animals. We can make mice smarter run twice as far protected from all those diseases. We haven’t found any side-effects yet that are negative. So we could have medicines that simultaneously protect the elderly or even the middle-aged person from some of the diseases that that that kill people. And the future I think is really bright you can imagine a future where a 90-year-old is just as healthy as a 50-year-old and still plays tennis. Maybe we see people reaching their hundreds when they can see their great-grandkids graduated from university. This is the future that I hope to see.”
“When I started this work, it was considered crazy to consider that you might find one gene or one drug that could really have a big impact on aging. That was because we used to think of our bodies like cars that would wear out and break down. We used to think of our bodies just like machines and actually medicine is practiced that way still.”
Sirtuins as Repairmen – David Sinclair
“But we actually have gone through a paradigm shift in thinking about aging in our bodies. What we now realize is that our bodies are far more complicated and intelligent compared to a car. So, for example, when a car gets damaged, or rusts or something breaks – the car doesn’t fix itself. In fact, if you fix the exhaust pipe it doesn’t mean that the scratch or the dent in the body will be fixed.”
“But our bodies are different. When we’re damaged, when we’re under stress, when we don’t get enough food, we actually seek our food – our bodies repair the damage. What we found out is these processes are not separate. There are these master regulators of defenses against disease, and some of these are the sirtuin genes that I work on. When we tweak the sirtuin1 gene – which is one of these sirtuins – it doesn’t just keep the paint shiny in you or repair the exhaust pipe, it fixes everything and makes the whole body more robust and fitter. That’s why we think we’re seeing this simultaneous protection against a heart disease and cancer and Alzheimer’s. It’s not miraculous; it’s just a new way of thinking about aging and realizing that we have inbuilt defenses against disease, and we just need to turn them on.”
David Sinclair’s Career Begins with Sirtuins
“When I left Australia, I went to work as a postdoctoral researcher at MIT Massachusetts Institute of Technology with an amazing man; he is still a good friend, Leonard Guarante. He and others in the lab were trying to understand why do yeast cells grow old. If we could understand why they grow old and die maybe we could find genes that control that process. Again, this was a crazy idea how could yeast tell us anything about human aging we get heart disease and cancer and yeast cells they’re just a single microscopic cell. But nevertheless, I thought that at least we should start with something simple because if we can’t figure it out for yeast, we have no hope of filling it up for humans.”
“What we did was we did find a cause of aging in yeast turns out their chromosomes get tangled and tend to choke the cell. Then there was a gene that was discovered that it slowed down this process called [unintelligible] – and that’s what gave the name to this whole class of genes called sirtuins. We actually have seven of those [sirtuins] in our body, and they seem to protect different organs from diseases.”
“Starting in 2003, I’ve been working to find and progress to the clinic molecules that can actually turn on these sirtuin defenses in our body. We’ve gone initially from extending lifespan in yeast cells through to little nematode worms and fruit flies. We’ve done this in obese mice we have some early interesting results even on lean mice that they might be living longer, but they’re certainly healthier and actually.”
David Sinclair on Human Testing of Sirtuin-Activating Compounds
“Now, these [sirtuin boosting] molecules have been worked on by hundreds of people. They’ve been improved in their potency and safety many-fold. They’re [sirtuin boosting molecules] in human studies right now in Europe and in the UK for different diseases of aging like for example type 2 diabetes or inflammation like arthritis and inflammation of the bowel. So these are areas that are either in-progress or in the future will be tested in the clinic.”
“Now, often people ask me ‘what’s the latest, are they working?’ Well, it’s too early to divulge, but I can say that the [sirtuin boosting] molecules have proven surprisingly safe so far in over 100 people. It’s still early days in terms of drug development, but over the next few years, we’ll certainly know if it’s going to be sooner or later that we can achieve this goal of having medicines that work on multiple diseases.”
“It’s a big effort; it’s gone way beyond my single laboratory. Now, there’s tens of millions of dollars being spent each year on these trials. We’ll have to see drug development is risky of course there’s no guarantee especially something as challenging as combating diseases of aging, but I’m optimistic the sciences is solid. The field of aging is now at the forefront of biology. If I’m not successful and these drugs don’t end up on the market, I think someone will have a breakthrough. We’ve had the paradigm shift – we know it’s possible it’s just a matter of time that we’ll have these remarkable drugs to treat the elderly and the sick.”
David Sinclair’s Closing Arguments on Sirtuins
“Often this sounds too good to be true that this might be the Fountain of Youth. I don’t like that to say that because people have tried for thousands of years to do this. Again, I have to be frank. I don’t know if this is going to be successful, but I do know that it will be possible one day it may be in the next few years maybe it’s another few decades. I don’t know but we’ve certainly turned a corner, and I think that the future of humanity looks bright if we can have medicines like this. I think dying in your 60s or being frail in your 80s may be a thing of the past. I hope to see that in my lifetime. Well if not, just help our kids. But, I think that medicine has a bright future, and I’m really excited to be part of it.”
Articles on Genetics and Sirtuins
- Dr. David Sinclair, Discoverer of Anti-aging NAD Fad, Speaks About Human Trials of NMN
- Old Human Cells Rejuvenated with ‘Breakthrough’ Anti-Aging Discovery (Sirtuin activating resveratrol analogs rejuvenate human cells)
- Can These Revolutionary Technologies Beat Aging in Our Lifetimes? (Watch this video which discusses how sirtuin-activating NAD works.)
- Does This Gene Fuel Obesity? (Variants of a gene called ‘ankyrin-B’ – a gene carried by millions of Americans – could cause individuals to put on pounds through no fault of their own.)
- Clinical trial shows NR and pterostilbene is safe and raises NAD levels.
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Dang, Weiwei. “The Controversial World of Sirtuins.” Drug discovery today. Technologies 12 (2014): e9–e17. PMC. Web. 1 Dec. 2017. Link.
The Sinclair Lab – David Sinclair. Harvard Medical School, Department of Genetics. Web. Retrieved Nov 13, 2017. Link.
Aging Reversed. “David Sinclair – Slowing down Aging.” Youtube. Jul 17, 2016. Web. Retrieved Nov 13, 2017. Link.
Photo Credits: All photos in this article are screenshots from the video “David Sinclair – Slowing down Aging.”
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