Do sirtuins actually do anything against ageing?

Sirtuins are a family of seven enzymes (SIRT1 through SIRT7) that only function when sufficient NAD+ is present in the cell. They regulate processes directly related to ageing: DNA repair, energy production in the mitochondria, inflammation, and the clearance of damaged cellular material. SIRT1 and SIRT6 have been studied the most and appear to play a protective role in multiple organs.

There is concrete and strong evidence from animal and cell studies. For example, SIRT2 activity in the main body artery declines as we age, both in mice and in humans. Mice lacking SIRT2 develop stiffer blood vessels and more inflammation more rapidly. SIRT3 plays a comparable role in bone marrow stem cells: in ageing mice, lower SIRT3 activity leads to a disrupted cellular clearance function, after which the stem cells age more rapidly and bone loss occurs. Administering extra SIRT3 to those mice reduced both stem cell ageing and bone loss. This has not yet been demonstrated in humans.

Another example: in older mice and humans, SIRT1 is lower in certain immune cells. This makes the liver more vulnerable to alcohol-related damage. In blood samples from patients, a lower SIRT1 level was associated with higher liver damage markers. This is an association, not proof that increasing SIRT1 reverses the damage.

The idea of stimulating sirtuins with medications or supplements is still in its early stages. NAD+ supplements (such as NMN) and other sirtuin-activating compounds are being investigated clinically for cardiovascular disease, but no hard results in humans have been published yet. Most of the usable data come from cell and animal experiments. The same applies to applications in skin ageing and kidney function: interesting mechanisms, but clinical evidence is currently lacking.