The NAD World 2.0: the importance of the inter-tissue communication mediated by NAMPT/NAD+/SIRT1 in mammalian aging and longevity control
Imai S, Guarente L
Published in npj Systems Biology and Applications
Abstract
Comprehensive review of the systemic NAD+ biosynthesis pathway involving NAMPT and its crucial role in aging and longevity. Demonstrates how declining NAD+ levels contribute to age-related diseases and how restoration may combat aging.
Methodology
Conceptual review synthesising mechanistic and animal research on NAMPT-mediated NAD+ biosynthesis, SIRT1 signalling and inter-tissue communication in mammalian ageing.
Key Findings
Systemic NAD+ availability declines with age across tissues, driven substantially by reduced NAMPT-mediated salvage synthesis. This decline impairs SIRT1-dependent regulation of metabolism, circadian rhythm and mitochondrial function. The authors propose the hypothalamus, adipose tissue and skeletal muscle as a control axis, with extracellular NAMPT acting as an inter-tissue signal. NAD+ precursors such as NMN and NR restore NAD+ and improve metabolic and functional measures in aged mice.
Conclusions
Declining NAD+ is presented as a central, potentially modifiable driver of mammalian ageing, and precursor supplementation is a plausible intervention target - a framework, not proof of human benefit.
Limitations
Theoretical review built on rodent and cell data; no human outcome evidence. Subsequent human trials of NAD+ precursors have reliably raised blood NAD+ but have not demonstrated the functional or longevity benefits seen in mice. Senior authors have commercial interests in NAD+ precursor research.
Outcomes Measured
Comprehensive review of the systemic NAD+ biosynthesis pathway and its crucial role in aging and longevity, demonstrating how declining NAD+ levels contribute to age-related diseases.
Systemic NAD+ availability declines with age across tissues, driven substantially by reduced NAMPT-mediated salvage synthesis. This decline impairs SIRT1-dependent regulation of metabolism, circadian rhythm and mitochondrial function. The authors propose the hypothalamus, adipose tissue and skeletal muscle as a control axis, with extracellular NAMPT acting as an inter-tissue signal. NAD+ precursors such as NMN and NR restore NAD+ and improve metabolic and functional measures in aged mice.
Systemic NAD+ availability declines with age across tissues, driven substantially by reduced NAMPT-mediated salvage synthesis. This decline impairs SIRT1-dependent regulation of metabolism, circadian rhythm and mitochondrial function. The authors propose the hypothalamus, adipose tissue and skeletal muscle as a control axis, with extracellular NAMPT acting as an inter-tissue signal. NAD+ precursors such as NMN and NR restore NAD+ and improve metabolic and functional measures in aged mice.
Systemic NAD+ availability declines with age across tissues, driven substantially by reduced NAMPT-mediated salvage synthesis. This decline impairs SIRT1-dependent regulation of metabolism, circadian rhythm and mitochondrial function. The authors propose the hypothalamus, adipose tissue and skeletal muscle as a control axis, with extracellular NAMPT acting as an inter-tissue signal. NAD+ precursors such as NMN and NR restore NAD+ and improve metabolic and functional measures in aged mice.
Study Details
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