• Mouse skeletal muscle maintains normal function despite an 85% reduction in NAD levels, contradicting established theories.
• NAD depletion did not lead to muscle weakness, accelerated aging, or impaired exercise performance in the studied mice.
• The study questions the efficacy of NAD-boosting supplements and highlights the need for tissue-specific research on NAD's role.

A new study published in Cell Metabolism challenges the prevalent belief that declining NAD levels are a primary driver of muscle aging and dysfunction. Researchers at the Novo Nordisk Foundation Center for Basic Metabolic Research found that mice with drastically reduced NAD levels (85% depletion) in their skeletal muscle maintained normal muscle structure, strength, exercise capacity, and aging trajectories. This suggests that skeletal muscle is more resilient to NAD deficiency than previously thought and raises questions about the effectiveness of NAD-boosting supplements often marketed for anti-aging benefits.

• What: A study found that mouse skeletal muscle can maintain normal function despite losing 85% of its NAD content.
• Who: Researchers at the Novo Nordisk Foundation Center for Basic Metabolic Research; Sabina Chubanava, Jonas Treebak (study authors); Daniel Puleston (oncological sciences professor); Jennifer Aniston (celebrity promoting NAD+).
• When: Study published in Cell Metabolism in May 2025; mice tracked for nearly two years.
• Where: Research conducted at the Novo Nordisk Foundation Center for Basic Metabolic Research.

The study's findings challenge the widely held belief that declining NAD levels are a primary driver of muscle aging and dysfunction. While previous research has associated NAD depletion with age-related decline, this study demonstrates a surprising resilience in skeletal muscle. The research suggests that the role of NAD in aging and muscle health may be more nuanced than previously thought, and that NAD-boosting supplements may not be as effective as advertised, at least for healthy skeletal muscle. Further research is needed to understand the specific conditions under which NAD depletion becomes detrimental and to investigate the tissue-specific effects of NAD.

Skeletal muscle exhibits markedly greater resilience to NAD depletion than previously thought.

Contrary to what might have been expected, healthy skeletal muscle function is not as reliant on high levels of NAD as previously thought. Importantly, our findings indicate that reducing muscle NAD levels well beyond the modest drops seen with normal aging does not cause muscle weakness or make the muscle age faster.

Our results suggest that skeletal muscle can tolerate substantial NAD depletion without loss of function or accelerated aging. This challenges the prevailing view that NAD+ decline is a primary driver of muscle aging and frailty.

The recent study provides compelling evidence that skeletal muscle is more resilient to NAD depletion than previously believed. While NAD remains an essential molecule for cellular function, the findings suggest that moderate NAD depletion may not be as detrimental as once thought, particularly in healthy skeletal muscle. This research calls for a re-evaluation of the role of NAD in energy metabolism and age-related decline and raises questions about the efficacy of NAD-boosting supplements. Future research should focus on identifying the specific conditions and tissues where NAD depletion has significant impacts on health and aging.