Sirtuins, NAD+ and Aging

As someone who is passionate about maintaining their health and vitality as they age you will be keen to learn about the latest science surrounding the aging process. If so, this article will describe what sirtuins are, how they are linked to NAD+ and why Prof David Sinclair views sirtuins as a key pathway in aging biology.


Sirtuins were initially discovered in yeast and interest grew when studies revealed that increasing expression of SIR2 (the yeast form of sirtuins) extended the lifespan of the yeast by 30%. David Sinclair continued this work in the lab of Prof Leonard Guarente to see if these results could be translated to other animal models. When studying mice, they found that increasing expression of SIRT1 (the mammalian equivalent of yeast SIR2) improved their health. Since these initial studies, David Sinclair has been a pioneer in studying sirtuins, looking into their function and role as ‘longevity genes’.

Humans have seven sirtuin proteins (SIRT1-7) and although they are very similar in structure, they have different functions and are found in different locations within the cell.  SIRTs 1,6 and 7 are found in the nucleus, SIRTs 3,4 and 5 are found in the mitochondria and SIRT2 is found in the cytoplasm. Sirtuins are known to impact a wide variety of cellular processes including regulating gene expression, metabolism, supporting mitochondria, supporting DNA health, and regulating circadian rhythms (our internal body clock).

Sirtuins are so vital to our cellular health that they are found in every cell and have been conserved throughout evolution.

Sirtuin functions

Sirtuins regulate gene expression

Our DNA contains different markers which can be added or removed. The pattern of these markers helps to instruct the cell which genes to express and when. This is called epigenetics and allows  the cell to react to environmental changes by altering which genes are expressed.

Each cell contains the same set of instructions (DNA), but every piece of information held within the DNA is not needed all the time. For example, when we are young and growing, we express developmental genes. However, these genes are not needed when we are adults.

One type of epigenetic marker is an ‘acetyl group’. When acetyl markers are removed from DNA, it becomes tightly coiled concealing the genes. This means some genes become inaccessible to the cellular machinery that ‘reads’ DNA so they remain switched off. Sirtuins work by removing acetyl markers from sections of DNA which effectively switches off target genes.


NAD is the fuel for sirtuins

So how are sirtuins and NAD+ linked? Well, NAD+ is the fuel for the reactions carried out by sirtuins - so without NAD+ sirtuins simply don’t work! Therefore, when NAD+ levels decline with age, so does sirtuin activity and this is a key reason why interest in maintaining NAD+ levels has grown.

 NAD+, Sirtuin decline with age

Lots of research has focused on finding the best way to maintain sirtuin activation as we age and scientists agree that the best ways to do this is by maintaining your NAD+ levels. Sirtuin activity has also been found to increase in response to cellular stress such as exercise and fasting, which are both known to increase NAD+.


Aging is the most complex biological process

As with all things in biology, aging is an extremely complex process involving many different proteins, pathways and feedback loops. As our understanding of cellular aging grows, it is now known that age related NAD+ decline is linked to many of the signs of aging we feel, and this is partly due to a decline in sirtuin activity.

In light of this complexity, any attempt to boost NAD+ levels and sirtuin activity requires a multi-targeted solution looking at the entire NAD/Sirtuin network and identifying the precise parts which can be altered to have a positive impact. This is the exact approach Nuchido TIME+ takes, using a combination of ingredients that target various aspects of the NAD/Sirtuin network. This approach has been shown to increase NAD+ levels by 242% in our pilot study and also increase sirtuin activity.


According to David Sinclair, sirtuins are one of the key pathways essential to longevity due to their beneficial roles in supporting cellular health. Therefore, making sure they remain active as we age should be a priority. However, sirtuins are dependent on NAD+ to function which is why combating age-related NAD+ decline is so vital.


Read more about David Sinclair’s insights into longevity and NAD+ along with the importance of a multi-targeted approach to effectively address the complex biology associated with it