Lifespan.io has launched their latest crowdfunded study, and seeks more donors to join the more than 100 philanthropists of our community who have pledged already in the first few days. It is an assessment of the capacity of nicotinamide mononucleotide (NMN) to slow aging in mice, treating both normal mice and a lineage exhibiting accelerated aging. The final stretch goal in this fundraiser will provide enough funding to kick off a full life span study. This work is carried out in partnership with David Sinclair's lab, home of the past fifteen years of work on calorie restriction mimetics associated with sirtuins, a line of research that has evolved to these days to focus instead on nicotinamide adenine dinucleotide, NAD+.
NMN is one of a number of options that can be used to treat the loss of NAD+ in older individuals. While this approach doesn't address any of the causes of aging, meaning the rising levels of molecular damage that take throughout the body, it does serve to boost mitochondrial function. Mitochondrial function is well known to falter with age, and researchers consider this important in a range of age-related conditions. The evidence to date suggests that enhancing NAD+ levels may to some degree diminish measures of aging. To pick one recent example from the data, a small human trial of nicotinamide riboside, another of the options to raise NAD+ levels, demonstrated a reduction in blood pressure in hypertensive older patients.
One of the best studied anti-aging treatments is a diet reduced in calories, yet high enough in nutrients to avoid malnutrition. Known as calorie restriction (CR), this dietary regimen provides irrefutable evidence of the importance of metabolism in the aging process. While CR has been studied extensively and even tested in human trials, long term adherence to a CR dietary regimen is extremely difficult for most individuals to maintain.
One method to achieve the benefits of CR for everyone would be to administer compounds which act as "CR mimetics". A major metabolic signaling molecule that we and others have shown to exhibit significant declines with increasing age is NAD+. Importantly, CR reverses the age-related decline of bioavailable NAD+. This key metabolite plays a crucial role in regulating the activity of many important signaling molecules involved in age-related diseases.
However, feeding or administering NAD+ directly to organisms is not a practical option. The NAD+ molecule cannot readily cross cell membranes to enter cells, and therefore would be unavailable to positively affect metabolism. Instead, precursor molecules to NAD+ must be used to increase bioavailable levels of NAD+. Recently, we have shown that by administering the NAD+ precursor NMN (Nicotinamide Mononucleotide) in drinking water to older mice, NAD+ levels were restored to those normally associated with younger healthy animals. By administering NMN to mice for just one week, our lab demonstrated a robust correction in age-associated metabolic dysfunction and restored muscle mitochondrial function in old mice to levels seen in younger control mice.
Although the restorative properties of NMN treatment drive many of the same cellular signaling pathways which underlie CR, trials of greater than one week or two months are needed to properly evaluate whether NMN can reverse the aging process. Starting with mice that are 20 months old (roughly equivalent to a 50 year old human), longer-term NMN treatments will be applied in order to restore levels of cellular NAD+ to those found in youthful mice. Along with a large cohort of normal mice, we will also use a cohort of our novel genetically engineered mouse, termed the ICE mouse (Induced Changes In Epigenome). These ICE mice manifest an accelerated aging phenotype.
Your donations will not only allow us to purchase the materials necessary to perform this experiment, but also pave the way for human clinical trials aimed at showing, for the first time, that we can actually slow down human aging. We find ourselves at a turning point in history, and together we have the chance to accelerate technologies that will allow us to live healthfully at any age. This is a future that is coming, and whether it arrives in our lifespan or only for future generations is up to us.