If you have been delving into longevity supplements like NAD+ and NMN lately, you must have heard about sirtuins. Sirtuins are a family of seven signalling proteins involved in several metabolic processes. While these proteins are found in the nucleus, cytoplasm, and mitochondria of human cells, mitochondrial sirtuins have especially been the focus of research for the last couple of years for their role in longevity.
When were sirtuins discovered?
They were first discovered in the 1970s when researchers found that some signalling proteins regulate certain parts of the chromosomes, i.e., histones (2). Histones are proteins that provide structural support to chromosomes and act as spools for the DNA to wrap around. Researchers found that they prevent DNA damage, promote DNA repair and regulate the cell cycle (3).
Functions of sirtuins
Furthermore, sirtuins regulate energy metabolism, stress resistance, inflammation, circadian rhythm, and neuronal function (4)(5). But the most important role sirtuins play is determine how fast you will age. Sirtuins regulate the spooling and unspooling of histones and indirectly control the DNA that is wrapped around the spool. Since only unwrapped DNA can be expressed — the process by which a gene's information is used to make a useful product for the body — sirtuins turn on or off the genes that control aging and increase longevity.
However, they require NAD+ for activation, and NAD+ requires NMN and other substrates. Unfortunately, the levels of both NMN and NAD+ fall off the cliff as we age, so much so that by the time we are in our fifties, we only have half the amount of NMN and NAD+ we had in our twenties (9)(10). As a result, NMN, NAD+, and sirtuins have gained wide popularity in longevity medicine.
Sirtuins have emerged as an important class of aging regulators, and scientists have tried to understand their activators and inhibitors. Among others (like NAD+), resveratrol (a polyphenol compound) has also emerged as a powerful activator of sirtuins (11). While resveratrol and NMN can be found in many dietary sources, their amount is minuscule. So taking supplements is the best way to maintain a healthy amount of these important chemicals and proteins in the body.