Most of this work comes from mice
Sirtuins and NAD+ draw from the same supply
You’ll see which proteins use NAD+, what changed with age, and why the mouse findings don’t prove a benefit for you.
One protein may help lower NAD+ with age
Mouse work points to one cause. Your cells spend NAD+ on needed jobs. Sirtuins are proteins that switch some cell jobs up or down. Other proteins spend NAD+ while fixing DNA. A third protein breaks NAD+ apart and becomes more common with age. All three draw from one supply. Mouse tests link the NAD+-breaking protein with part of the age loss. Exercise and the body clock may also change how much your body replaces. These findings explain the interest. They can’t show that a product will help you. Study amounts here aren’t advice.
Sirtuins use NAD+ to switch cell jobs up or down
Sirtuins are proteins that act like switches. They use NAD+ to turn some cell work up or down. The work includes getting energy from food and mending DNA [5].
In 1 review, researchers studied a sirtuin in the cell parts that make energy. When mice lacked that sirtuin, those parts made less usable energy. Their cells also had less guard against damage [9].
The NAD+ supply can change how much work sirtuins do. That’s one reason researchers care about the drop linked with age [5]. The mouse work still doesn’t show that taking a pill would help your health.

DNA repair and one age-linked protein spend NAD+
One group of proteins mends damaged DNA. Those repairs can use a great deal of NAD+ [5]. A second protein breaks NAD+ apart. Bodies make more of that protein with age and during inflammation [5]. Inflammation here means an immune response inside tissue, not just a swollen ankle.
In 1 mouse study, animals without the NAD+-breaking protein kept more NAD+ as they aged. A sirtuin kept working in their energy-making cell parts, which made more usable energy [2]. A drug that blocked the same protein helped old mice handle sugar and fat [8]. Researchers also tested apigenin, a plant substance. First they used cells in a dish. Then they gave mice an injection of 100 milligrams per kilogram of the mouse’s weight. Those mice ate a high-fat diet. Their NAD+ rose, and their blood sugar control improved [10]. People weren’t tested.
Exercise and the body clock changed NAD+ in studies
One protein starts the work of turning used niacin back toward NAD+ [5]. Exercise can change how much of this protein your muscle holds. Trained people had about twice as much of that NAD+-making protein as people who didn’t train. Mice bred to make more of it ran about three times as long [7]. That mouse result doesn’t promise more strength for you.
Your daily body clock matters too. Clock proteins help set when cells replace NAD+. NAD+ rose and fell over 24 hours. Mice with a broken body clock lost that daily change [6].
That daily swing was real in mice [6]. It hasn’t shown a best time for people to take NAD+. The test gives no support for morning or night advice.