Dr. Sandra Kaufmann The Science of Slowing Aging

Sandra Kaufmann, M.D., is Chief of Pediatric Anesthesiology at Joe DiMaggio Children's Hospital in Hollywood, Fla.

The 49-year-old married mother of two is also an athlete who enjoys running, swimming, and rock climbing. When she hit her mid-40s, Kaufmann decided she didn't want to succumb to the ravages of time and began exploring ways to fight back against what has always been the inevitable decline of aging.

Armed with years of higher education that not only included her medical degrees but also a masters in ecology and evolutionary biology with an emphasis on cellular plasticity under changing environmental conditions, she scrutinized thousands of scientific studies on hundreds of potentially anti-aging substances.

The results are detailed in her new book, The Kaufmann Protocol: Why We Age and How to Stop It, available in e-book form from Amazon.com. In it, she describes the mechanisms of aging on a cellular level and the best substances to retard its progress.

Life Extension® caught up with Dr. Kaufmann a few days before she headed off on an expedition to the base camp of Mount Everest.

LE: It seems ironic that a children's doctor should become an expert in aging.

SK: I appreciate the irony but, on the other hand, spending so much time with kids serves to remind me that the clock is always ticking.

LE: How is your book different from the many other anti-aging books and programs on the market?

SK: My book is not about diet and exercise, and has little mention of carbohydrates or ketones. It doesn't include anything about colonic cleansing or any other fad or exotic treatment to prevent aging. My book is based solely on how to maintain cellular health. We are made of cells, and we age because our cells age. You have to change your perspective from organs to cells, from "what does my skin look like?" to "what are my skin cells doing?" You have to look inside the cells, which is what I have done.

LE: What are the mechanics of aging?

SK: Aging consists of seven categories of things that happen to your cells. No. 1: Changes to DNA, including epigenetic modification and telomere length. No. 2: Disruptions in energy production due to mitochondria failure. No. 3: Problems with metabolic pathways, especially the sirtuins, AMPK, and mTOR pathways. No 4: Quality control problems that affect DNA and protein repair. No. 5: Inflammatory issues due to a faulty immune system. No. 6: Not fulfilling the needs of specific cells. No. 7: Incomplete waste management.

To defeat aging, or decelerate the process, you have to take into consideration each of the seven categories.

LE: Are any of those seven categories more important than others?

SK: They are all interrelated and dependent on each other. The ratio of what's important may change over time. For example, when you are young, you have less DNA damage, so the DNA repair mechanisms are less active. As you get older, you have more DNA damage and less capacity to fix it, so that category becomes extraordinarily important. I separated the categories to explain the process. But in practice they are so interrelated it's virtually impossible to separate them.

LE: What's the basis of the Kaufmann Protocol?

SK: For every anti-aging agent I've identified, I've created a numerical system that rates it on a 0 to 3 scale for each of the seven categories of cell aging in the order I've already listed. For example, resveratrol and its more bioavailable cousin, pterostilbene, hits every category, carrying a Kaufmann Rating score of 2.3.3.3.2.2 for a total of 15. Carnosine, a dipeptide, has a Kaufmann Rating of 0.3.0.0.0.0.3 for six points.

LE: How does epigenetic modification come into play?

SK: Epigenetics is genetic control on top of your DNA. Every cell carries the same information, but the information you needed as a neonate you may not need as an adult. As the needs change, the methylation pattern of the DNA changes, blocking your body from transcribing that information. It's a control mechanism. You also have epigenetic drift, which is how the environment affects the methylation patterns. Chronic inflammation from things like chemical pollution, alcohol, smoking and UV light causes a negative methylation drift that can lead to aging and cancer. There are also beneficial epigenetic modifiers, such as sulforaphane, resveratrol and curcumin. So you can affect your genes positively by eating good things.

LE: How about telomeres?

SK: Telomeres are the ends of DNA that don't code for anything but act as protective caps. Every time a cell divides, you lose a length of telomeres, on average 50 to 70 base pairs a year. When you lose too much length, the cells can no longer divide. They become senescent, which is the equivalent of a grumpy old man sitting in the corner being obnoxious by spewing out evil cytokines and interleukins and making everything systemically inflamed.

LE: So how do you protect DNA?

SK: The best agents I've found are sulforaphanes, which you find in broccoli and other cruciferous vegetables; the medicinal plant astragalus; and the diabetes drug metformin.

LE: Why do you include a prescription diabetes drug in your protocol?

SK: I tried to include only things that anyone can easily buy, but metformin was too good to pass up. I call it the Clark Kent of the drug world because it looks old and stodgy but is actually Superman. It is an epigenetic modifier that induces genome-wide methylation and stimulates telomere length. It activates endogenous antioxidants to protect mitochondria from oxidative stress. It's an anti-inflammatory, boosts the formation of new nerve cells and, of course, reduces blood glucose. It is amazing in almost every category. One study said that metformin has saved more people from cancer than anything else. That's because it lowers both sugar and inflammation, two risk factors for cancer. It also promotes better gut bacteria. It's cheap as dirt and the only common side effect seems to be a bit of indigestion in some people. I think everybody should be taking it whether they have diabetes or not.

LE: What are metabolic pathways and how do they influence aging?

SK: The discovery of metabolic pathways came about from scientists trying to figure out why a calorie-restricted diet increased longevity in organisms pretty much across the board. When the body thinks it is starving, it triggers innumerable processes including turning metabolic pathways on and off. There are many pathways, and new ones being discovered all the time, but the big three are gene/protein combinations called AMPK, sirtuins and mTOR. AMPK is called the body's "metabolic master switch," and it maintains energy homeostasis by regulating the energy flow. There are seven members of the sirtuin family, and they sense the environment and alter the metabolism to promote survival. In part, they accomplish this by activating AMPK. The sirtuin family is dependent on the coenzyme NAD+ (nicotinamide adenine dinucleotide), which our bodies produce less of as we age. mTOR (mammalian or mechanistic target of rapamycin regulates growth and development, which is great when you are young. But as you age, excess mTOR activity contributes to inflammation and its numerous problems.

LE: Moving on to mitochondria…why do you call these little power stations "a necessary evil?"

SK: A long, long time ago, mitochondria were their own energy-efficient little cells that became engulfed by bigger cells and, eventually, semi-autonomous organelles within those cells. They're a victim of history because they evolved when oxygen was very rare, and now it's not rare. So mitochondria find themselves extremely vulnerable to free radicals. Mitochondria use oxygen, but get destroyed by it. The more they work, the more they damage themselves. It's kind of sad. Mitochondria make their own endogenous antioxidants, but over time can't make enough. Fortunately, there are several things that can help them out: astaxanthin, curcumin, quercetin, resveratrol or pterostilbene, and nicotinamide. When too many mitochondria are damaged, energy production drops, which affects all of the other categories and is why old people tend to feel tired a lot.

LE: Why is waste management so important?

SK: When you combine excess glucose and oxidative stress, you get advanced glycation end products, known by the wonderful acronym AGEs. AGEs age you because glucose is sticky and gums up the works of everything it latches onto, including DNA and proteins, eventually causing structural failure and dysfunction. It's why our arteries stiffen and skin sags. But several agents can either strip away AGEs or inhibit their formation. Some of the best are carnosine, curcumin, pyridoxamine (a form of vitamin B6), rosmarinic acid and our old friend metformin.

LE: You include 14 anti-aging "molecular agents" in your book. Do people have to take them all?

SK: The more the merrier. Although they may overlap to some degree, the biology is very complex and they sometimes work on different elements of the same problem. To start out, I recommend five agents that can be bought by anyone and touch all of the bases. I call them The Panacea. They all excel at supporting mitochondria, so the regime should give you an energy boost.

Resveratrol and pterostilbene score in every category but do especially well with metabolic pathways and DNA and protein repair. Astaxanthin is a super antioxidant that scavenges free radicals and acts as an anti-inflammatory. NAD (in the form of nicotinamide riboside) is a multi-tasker that is essential in activating the sirtuin pathways and is also vital in DNA repair. Curcumin, a molecule found in the spice turmeric, is another powerful antioxidant that is also an epigenetic modifier. Carnosine is one of my favorites because of its ability to block AGEs formation. It acts like the body's janitor in cleaning up the waste. Along with these agents, I also recommend that everyone take a good multivitamin because people suffer from micronutrient deficiencies and we don't want to starve our cells from the raw materials they need. Traditionally, we treat diseases. My protocol is designed to avoid diseases. I think this is the way the world will be going eventually.

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