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The Wnt-NAD axis in cancer, aging, and tissue regeneration.

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Trends in cell biology 2026 Vol.36(2) p. 154-174
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Lamprecht J, Abu Sanad S, Kusumbe AP, Habib SJ

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The intricate interplay between Wnt signaling and nicotinamide adenine dinucleotide (NAD biosynthesis has emerged as a crucial axis that influences aging and tissue regeneration.

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APA Lamprecht J, Abu Sanad S, et al. (2026). The Wnt-NAD axis in cancer, aging, and tissue regeneration.. Trends in cell biology, 36(2), 154-174. https://doi.org/10.1016/j.tcb.2025.07.006
MLA Lamprecht J, et al.. "The Wnt-NAD axis in cancer, aging, and tissue regeneration.." Trends in cell biology, vol. 36, no. 2, 2026, pp. 154-174.
PMID 40885694 ↗

Abstract

The intricate interplay between Wnt signaling and nicotinamide adenine dinucleotide (NAD biosynthesis has emerged as a crucial axis that influences aging and tissue regeneration. Wnt signaling, a key regulator of cellular proliferation, differentiation, and tissue homeostasis, intersects with NAD metabolism, a cornerstone of cellular energy balance and genomic stability. This relationship is mediated through shared regulatory pathways involving sirtuins, poly(ADP-ribose) polymerases (PARPs), and metabolic enzymes which are sensitive to cellular NAD levels. Dysregulation of either pathway is implicated in cancer, age-related decline, and impaired regenerative capacity. This review consolidates current knowledge of the Wnt-NAD axis and highlights its cooperative roles in maintaining tissue integrity and combating the effects of aging. Furthermore, it explores therapeutic approaches targeting this axis to restore tissue health and enhance the capacity for repair, thereby offering promising avenues for addressing age-associated pathologies.

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