Review: dual role of NAD+ metabolism in muscle stem cells during age-related sarcopenia
This hypothesis-driven review of nearly 60 preclinical and clinical studies describes how NAD+ can support muscle stem cells at moderate levels but may exhaust them under aging or pathological conditions. [1]
Automatic summary · not editorially reviewed
The key findings
Sarcopenia is described as an age-related syndrome with progressive loss of skeletal muscle mass and function, closely associated with impaired regenerative capacity of muscle satellite cells. [1]
Moderate NAD+ repletion via precursors such as NMN or NR is said to activate SIRT1 and SIRT3 and promote MuSC proliferation and myogenic differentiation. [1]
The review integrates evidence from nearly 60 representative preclinical and clinical studies and proposes future directions for NAD+-targeted therapies for sarcopenia. [1]
The source at a glance
- Study type / format
- Hypothesis-driven narrative review of preclinical and clinical studies (abstract)
- Population / context
- People with age-related sarcopenia and muscle satellite cells studied in preclinical and clinical research
- Summary based on
- Study abstract
- Original publication
- June 5, 2026
Sarcopenia and the aging muscle stem cell niche
Sarcopenia is described as an age-related syndrome with progressive loss of skeletal muscle mass and function, closely associated with impaired regenerative capacity of muscle satellite cells (MuSCs). During aging, the MuSC niche deteriorates, including mitochondrial dysfunction, chronic inflammation and degeneration of the neuromuscular junction; these compromise MuSC quiescence, proliferation and differentiation.
Supporting source [1]
Moderate versus excessive NAD+ signaling in MuSCs
NAD+ is presented as a coenzyme and signaling molecule governing MuSC homeostasis in a context-dependent, dual-function manner. Moderate repletion via precursors such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR) is said to activate SIRT1 and SIRT3, enhance mitochondrial bioenergetics, reduce oxidative stress and promote MuSC proliferation and myogenic differentiation. Under pathological or aging conditions, excessive or dysregulated NAD+ signaling is said to activate SIRT2, which deacetylates PAX7 and represses Myogenic Differentiation 1 (MyoD), leading to cell-cycle arrest and MuSC exhaustion.
Supporting source [1]
Review scope: integrated evidence and proposed directions
The review uses a hypothesis-driven framework to summarize molecular crosstalk between NAD+ metabolism, sirtuin family deacetylases (SIRTs) and MuSC fate regulation. It integrates evidence from nearly 60 representative preclinical and clinical studies, clarifies the dual-function role of NAD+ and addresses current inconsistencies in the field. It also highlights key limitations and proposes future directions for developing NAD+-targeted therapies for sarcopenia; these are proposals, not established treatments.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. The review is hypothesis-driven and draws on preclinical and clinical studies, so the described NAD+ effects and proposed therapies are not established treatments.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Li C, Ai Y, Yan J, Wu S. · europepmc.org · June 5, 2026