Sirtuins

A family of enzymes that remove chemical tags from proteins using NAD+ as a substrate, linking cellular energy status to gene regulation and repair.

What they do

Sirtuins are enzymes that strip acetyl groups from proteins, including histones, which changes how genes are read. There are seven in humans, working in different compartments: SIRT1 mainly in the nucleus, SIRT3 in mitochondria, SIRT6 in DNA repair and genome stability.

The key detail is that they require NAD+ as a co-substrate, consuming it in the process. That makes their activity dependent on cellular energy state, and it is the entire reason NAD+ became a commercial category.

Where the evidence is strong and where it is not

The biochemistry is well established, and sirtuin overexpression extends lifespan in some model organisms, though the size and reproducibility of those effects were disputed for years and depend heavily on genetic background.

The resveratrol chapter is instructive. Resveratrol was reported to activate SIRT1 and reproduce aspects of caloric restriction. Later work showed much of the measured activation was an artifact of the fluorescent assay used, and human trials of resveratrol have been largely disappointing. The mechanism survived; the product did not.

What this means for supplements

Raising NAD+ raises the substrate available to sirtuins, which is a sound rationale, and it is why NAD+ precursors are studied at all. It is not evidence that a specific supplement produces a durable functional change in a healthy adult.

Read sirtuin claims as a pathway story. Ask separately what the human trial measured and how long it ran.

Baseline offers NAD+ as a program add-on and describes it as supportive rather than proven, which is what the trial base supports.

References

  1. Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014.
  2. Pacholec M, et al. SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem. 2010.
  3. Bonkowski MS, Sinclair DA. Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds. Nat Rev Mol Cell Biol. 2016.