Mastering Longevity

Highlighted telomere ends on chromosomes
Highlighted telomere ends on chromosomes

The Science of Longevity

Throughout history, there have been claims that a person could live forever or grow young again. In his writings, Herodotus mentioned a spring called the Fountain of Youth, supposedly in Ethiopia, that allowed the people there to remain young. Apocryphal stories suggested that Juan Ponce de León searched for the Fountain of Youth in Bimini. Other stories mentioned elixirs of life or magical trees whose fruit could make you young. I strongly suspect that many religions may have grown more popular due to their promises of immortality after death. Many con men have taken advantage of the lure of an extended life span. It is only in recent years, that science has began to unravel the mysteries of aging. As we begin to understand the aging process, true life extension is coming within our reach.

First of all, we have learned that aging is cellular senescence, in other words our cells grow old. Heart disease, arteriosclerosis, diabetes (type II), arthritis, osteoporosis, hypertension, Alzheimer's disease, and gout are almost always a symptom of our cells growing old. Even cancer is usually due to the immune system growing old and being unable to protect the body against rogue cells, which is why cancer is so much more prevalent in old people compared to young people. Most medical treatment of these diseases is basically trying to alleviate a symptom that is basically the result of our cells growing old.

The main goal of longevity is to reduce or reverse cellular senescence. We want to make our cells get young again. If we could do that then probably 90% of human diseases would be cured too. Here is what we know so far about cellular senescence and potential avenues for extending life.

  • On the ends of our chromosomes are repeating pieces of DNA called telomeres. Each time a cell reproduces, its telomere gets shorter. After the telomere gets to short, the cell won't reproduce anymore. This is known as the Hayflick limit. The Hayflick limit helps to protect our body from cancer by limiting the maximum number of cell divisions. Most cancer cells contain an enzyme called telomerase that is able to restore the length of the telomeres. Young rapidly growing embryos produce telomerase to keep their telomeres long. The telomerase enzyme allowed our cells to reproduce freely. As we age, only stem cells and white blood cells continue producing high levels of telomerase. An experiment done at Harvard Medical School has shown that giving telomerase to mice, that were genetically predisposed to rapid aging, will cause them to be young again. We will have to wait for the results of experiments on normal mice to learn more about the possibility of a telomerase therapy for normally aging cells. There is also research being done on telomerase inhibitors for cancer treatment. This seems like contradictory goals for telomere research. Too much telomerase and we become susceptible to cancer, too little telomerase and our cells stop dividing. It is quite possible that we may learn that our cells do an excellent job of regulating their telomerase activity already, and that this may be a dead end in our research. Luckily there are other avenues to pursue for longevity.
  • Cells begin producing less hormones as we age. Hormones are chemicals that signal your body to do different things. They usually change slowly over the day, months, or years. They are involved in controlling cycles of sleep, menstruation, and growth. As we age, our genes instruct our cells to produce less hormones. This is probably due to our evolutionary heritage. Our DNA has optimized our ability to reproduce by sacrificing longevity. Luckily, restoring hormone levels to that of our younger days is fairly easy. Melatonin is a master hormone made by the pineal gland that regulates other hormones. In experiments with older mice, giving them extra melatonin extended their lifespan by 17% (871 days vs. 743 days). You can keep your melatonin levels naturally high by getting plenty of sleep in a dark room and making sure there is enough tryptophan in your diet. As you get older, you might want to start taking melatonin. A 17% increase in lifespan for a human would be about 10-15 years of additional life for most of us.
  • Immune cells reduce their communications with each other through different molecules called cytokines. Some cytokines (tied to IL-2) are mainly used by your immune system to regulate your body's defense to foreign invaders (bacteria, fungus, viruses) and rogue cells (cancer). Some cytokines (mainly IL-17) produce inflammation telling your body to send immune cells to attack those areas. As we get older there tends to become an imbalance in our cytokines. Our cells tend to produce significantly less IL-2 and more IL-17. This results in many inflammatory diseases, while also reducing our ability to defend against foreign invaders and many cancers. Research at the NIA (National Institute of Aging) suggests that small amounts of lenalidomide (a derivative of thalidomide) may promote IL-2 while inhibiting IL-17. Tests also showed that the subjects T-cells lived longer and were more active.
  • Our mitochondria slow down. The mitochondria are the energy producers in our bodies and as they do their job, they suffer oxidative damage. Free radicals produced by the metabolizing of food to create energy sometimes damage the structure of the mitochondria. The best known way of slowing this down is through caloric reduction. By reducing calorie intake, we can extend the life span of animals. Several researchers also are trying to find ways to revitalize the mitochondria through molecules that activate the sirtuin family of proteins. This is based on research done with resveratrol and later with SRT-1720. There have been some reports that there may be some serious flaws in the research done in this area due to a flaw in experimental methodology. We will have to wait a few more years to find out. Other researchers are reporting possible drugs that may revitalize mitochondria. Hopefully though, we will soon have a pill that will rejuvenate our cells and give them more energy. For now, the best solution may actually be to take melatonin. It turns out that melatonin is now only a master hormone, but it is also a powerful anti-oxidant. So melatonin may have dual anti-aging effects in the body.

There is tremendous progress being made in biochemistry and the rate of research is accelerating. New tools are allowing us to understand the mechanics of aging. Statistics are showing us behaviors that are harmful. Just seven things - exercise, eat right, don't smoke, avoid excessive drugs and alcohol, stay mentally active, take vitamins, and later take melatonin - and you can expect your body to make it to at least a hundred. I believe that is a reasonable goal in our day and age. It is my hope that soon, we will be making advances in longevity as fast as we age. I expect research on revitalization of mitochondria to add a couple more decades. It gives me strong motivation to stay healthy and safe.

Live long and prosper

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