Reversing Aging by award-winning author Mark Kingston Levin,PhD Some of the People and Science Behind the Breakthrough
Figure 1. Photo of Lenny Guarente of MIT is a key discoverer of some of the key factors in aging.
It all started with human development millions of years ago. Then the development of science and medicine for centuries. Are we on the verge of reversing aging in humans? Major steps by thousands of great biologists and other scientists such as Darwin was a major factor for progress in biology. In 2000, Imai et al suggested the relation between yeast lifespan and NAD+. About that same time, Guarente reported that NAD fuels the activity of sirtuins, including SIRT1—the more NAD there is in cells, the more SIRT1 does beneficial things. The induce formation of new mitochondria was also suggested. NAD activates another sirtuin, SIRT3, which is thought to keep mitochondria running smoothly.
Sirtuins were involved, specifically SIRT1 homolog as a NAD+-coupled enzyme are link. As early as 2004, Brenner and Bieganowsky found NR in milk and determined itss role in making NAD+. Nicotinic acid (NA) was used to improve heart health even though many people feel flushed as reported by Karpe and Frayn in 2004. In 2007 genetic evidence shows ways NAD+ can be made by nicotinamide riboside (NR) and its effect of increasing lifespan in yeast, Belenky et al.
In 2012, researchers astonished the world when they showed that when given doses of NR, mice on high-fat diets gained 60 percent less weight than they did on the same diets without NR. This work was responsible for getting the market for NR started. None of the mice taking NR showed signs of diabetes, and their energy levels improved. Scientist at Harvard reported in 2013 that they uncovered a secret that aging in mammals may be reversible. This research was a joint project between Harvard, the Institute for Aging and University of New South Wales Australia.
Figure 2. Shows the nucleus of the cell to the left and the mitochondria and cytosol to the right all in a cell.
The key factor in this discovery involves understanding how the cells communicate using molecules inside cells between the nucleus and mitochondria. They showed that as this molecular communication method get older they fail to function and increasing the rate of the aging processes.
Figure 3. Depicts fibroblasts taken from an aged human. The red represents the patient’s mitochondria showing branched networks. The blue shows their nuclear DNA and green is damaged DNA. (Image: Glyn Nelson/Flickr)
These factors were overcome by restoring the communication network in older mice using NAD+ also known by its proper name nicotinamide adenine dinucleotide. The amazing result from this study headed by David Sinclair showed tissue samples of a much younger mouse, thus reversing the age of the original old mouse.
Nicotinamide adenine dinucleotide (NAD+), shown below in Figure 4, was injected in to several older mice making them appear younger during this research. This research appears to indicate that aging is reversible as very fortunate thing for us older folks who want to feel younger again.
Figure 4. Shows a photo of David Sinclair now at Harvard but was born and raised in Australia.
Figure 4. Structure of nicotinamide adenine dinucleotide, oxidized (NAD+). (Image: NEUROtiker/Wikimedia)
While there’s promising test-tube data and animal research regarding NAD+ human clinical results are limited to showing 1) NAD is not toxic to humans and 2) levels of NAD+ do increase when taking supplements now marketed as Niagen and other Brands such as Basis. Recent work shows NR serves as a promoter of NAD levels found in mice and men. Human trials with NR and pterostilbene were shown to be safe and effective in increasing NAD+ level in humans in a RANDOMIZED, DOUBLE-BLIND CONSTROL STUDY IN 2017 by Guarente Group.
The story took off toward the end of 2013 with a high-profile paper by Harvard’s David Sinclair and colleagues. Sinclair, recall, achieved fame in the mid-2000s for research on yeast and mice that suggested the red wine ingredient resveratrol mimics anti-aging effects of calorie restriction. This time his lab made headlines by reversing aging in mice.
Sinclair’s report sparked excitement about NR, which was already on the market as a supplement called Niagen. Niagen’s maker, ChromaDex, a publicly traded Irvine, Calif., company, sells it to various retailers, which market it under their own brand names. In the wake of Sinclair’s paper, Niagen, Basis and other similar brands were hailed in the media as potential blockbusters.
The NAD findings tie into the ongoing story about enzymes called sirtuins, which Guarente, Sinclair and other researchers have implicated as key players in conferring the longevity and health benefits of calorie restriction. What is the way this new science can make you younger and feel better?
The Sinclair team’s paper focused on a new mechanism that NAD and sirtuins work together. They discovered that cells’ nuclei send signals to mitochondria that are needed to maintain their normal operation. Sirtuins such as SIRT1 helps insure the signals get through. As NAD levels decrease, SIRT1 activity decreases disrupting the system leading to rapid aging and eventually death.
Resveratrol was in the news about aging for many years but recently researcher such as Kumar et al Oxford, Miss., have quietly shown that pterostilbene is a kind of extra-potent version of resveratrol. The pterostilbene molecule is nearly identical to resveratrol’s except for a couple of differences that make it more “bioavailable, according to studies on pterostilbene; it gets into the bloodstream faster than resveratrol according to research at the Department of Agriculture and the University of Mississippi in Oxford. Agnes Rimando and A. Kumar et al have shown the role of pterostilbene in human health, therefore its role as a human supplement. Test-tube and rodent studies also suggest that pterostilbene is more potent than resveratrol when it comes to improving brain function, warding off various kinds of cancer and preventing heart disease.
Figure 6. Agnes Rimando of the Department of Agriculture in Oxford Mississippi has made discoveries that relate to human health.
Others at University of Mississippi Medical Center recently conducted human trails on pterostilbene to reduce blood pressure. The use of pterostilbene in humans. Some human health advocates take pterostilbene and NR as supplements in preventing and reversing aging. I am planning to try this new combination.
Figure 7. Investigating pterostilbene at the University of Mississippi Medical Center are (from left) Michael E. Griswold, director of UMMC’s Center for Biostatistics; Justin J. Sherman, associate professor of pharmacy practice; Krista D. Riche, clinical pharmacy specialist at St. Dominic Hospital; and Daniel M. Riche, assistant professor of pharmacy practice and medicine. UM photo by Jay Ferchaud.