From as long as we have recorded history there has been an attempt to live forever, either here on Earth, or in a better place. Egyptians mummified their important dead so they could live on in the afterlife. Vikings believed we would live on in Valhalla, and Judeo-Christians believe in a more spiritual existence in Heaven. But before taking a step into the great unknown most of us still in our mortal bodies hope for a long and healthy life. The search for immortality is written into our history with people like Ponce de Leon looking for the fountain of youth. Today that search continues but with modern science we are now looking into our own genes for the answer.
Before I get into the details of the genetics that may lead to us living as long as we want, I would like to introduce one of my heros, Aubrey de Grey. Very much like myself, a software engineer in love with artificial intelligence, he changed his focus to biology after meeting his future wife, fruit fly geneticist, Adelaide Carpenter. When her boss needed someone who knew about computers and biology to take over the running of a database on fruit flies. He educated himself in biology by reading journals and textbooks, attending conferences, and being tutored by his wife.
Aubrey was granted a PhD by Cambridge based on his book, The Mitochondrial Free Radical Theory of Aging, where he suggested that eliminating the damage to mitochondrial DNA may extend lifespan as his book proposed, it was the accumulation of damage to DNA that caused the cell to become senescent, and commit suicide and die. In short, damage to the mitochondrial DNA was the basis of aging. Essentially, de Grey has described death as a type of disease that can be avoided, and the things that happen to us in life that have eventually led to death can be treated, and not only can be death be forestalled, but that our healthspan can be lengthened along with our lifespan. Given enough time, research and funding, it is the belief of a growing number of people that the disease and ravaging of our cells that have ultimately led to our death’s can be overcome.
Today, there are a growing number of scientists focused on life extension through varied mechanisms. This article focuses on the importance of the mammalian Sirt1 gene, also known as the “longevity gene.” For those without a molecular biology background, our genes are made up of DNA, which is a code, that when read by enzymes, create proteins that do things in our bodies. The Sirt1 gene encodes NAD-dependent deacetylase sirtuin-1, or simply sirtuin 1.  Don’t let your eyes glaze over just yet. The Sirt1 gene is known to be one of the regulators of autophagy, or the process where cells destroy and recycle parts of our cells. When reacting to disease, the process adapts to stress and promotes survival of the cell. This is accomplished by regulating cell proteins such p53, FoxO and Ku70 which set the threshold for when a cell dies by suicide or sets to repairing itself.  But in one unique case, when the cell is presented with starvation, the autophagy process promotes cellular survival by maintaining cellular energy levels. This has become the basis of an extreme diet known as calorie restriction. People live on the bare and almost unsustainable levels of calorie intake (20% to 40% reduced caloric intake), essentially keeping their cells in the autophagy state where cell survival is promoted.
Most of us have trouble skipping dessert, and the idea of literally starving ourselves is a pretty extreme notion. Enter resveratrol. Yes, I had to practice saying it too. This is a natural compound found in red wine (specifically in the skin of red grapes), and several kinds of berries. Resveratrol has been found to marginally increase levels of Sirt1 in humans. Since its first beneficial discovery, resveratrol has become a standard supplement for those seeking a longer life. More recently, a derivative of resveratrol, pterostilbene, has been shown to be better absorbed and more potent. In fact, some studies have shown that resveratrol might slightly raise Sirt1 levels but only has a side effect of other processes where pterostilbene apparently raises these levels directly. Plants, in particular blueberries, normally produce pterostilbene in response to injury and infection. In humans, it acts in a way similar to calorie restriction triggering the cells to release healing chemicals such as adiponectin. So, what does that mean for us? Studies have shown that pterostilbene has anti-cancer benefits, regulation of neurological diseases, improves the condition of diabetes and reduces inflammation and vascular disease.
Another supplement that activates Sirt1 is nicotinamide riboside (NR). NR is found in trace amounts in milk and is a precursor to our cells’ level of a chemical known as NAD. (Read my article about NAD+ and NR)
Summing it all up
Sirt1 is a protein that is associated with the regulation of cell repair, or programmed cell death. Increasing levels of Sirt1 by calorie restriction or through supplementation (which mimics the effects of calorie restriction) can extend healthspan, and in some mammals such as mice, significantly extend their lifespan. Supplements that raise levels of Sirt1 include resveratrol, slightly, and pterostilbene, significantly and nicotinamide riboside which raises the NAD levels in cells. Whether actual life extension can be achieved through supplementation is a very controversial topic. But the science is headed in the right direction and it looks very promising.
As always, live longer,
- Timmers, et al., Calorie restriction-like effects of 30 days of Resveratrol (resVida™) supplementation on energy metabolism and metabolic profile in obese humans, Cell Metab. 2011 Nov 2; 14(5): 10.1016/j.cmet.2011.10.002.
- Cantó C et al., The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity., Cell Metab. 2012 Jun 6;15(6):838-47. doi: 10.1016/j.cmet.2012.04.022.