Table of Contents

NAD⁺ Biology in Ageing and Chronic Disease: Mechanisms and Evidence across Skin, Fertility, Osteoarthritis, Hearing and Vision Loss, Gut Health, Cardiovascular–Hepatic Metabolism, Neurological Disorders, and Muscle

Published on: 26th January, 2026

Background: Nicotinamide adenine dinucleotide (NAD⁺) is a pivotal coenzyme and signaling substrate that integrates redox balance with mitochondrial energy production, DNA repair, epigenetic control, and cellular stress resilience. Declines in NAD⁺ availability—frequently observed with ageing, chronic inflammation, and metabolic stress—have intensified interest in NAD⁺ restoration as a potential strategy to influence disease biology across multiple organ systems.Objective: This narrative review summarizes contemporary mechanistic and translational evidence on NAD⁺ biosynthesis and turnover, highlighting the de novo kynurenine pathway and vitamin B3–dependent salvage routes (nicotinic acid, nicotinamide, nicotinamide riboside, and nicotinamide mononucleotide). We also examine how major NAD⁺ consumers and sensors, sirtuins, poly(ADP-ribose) polymerases (PARPs), and CD38 link NAD⁺ status to inflammation, oxidative stress, and tissue dysfunction in diverse clinical contexts.Methods: Peer-reviewed literature on NAD⁺ metabolism, NAD⁺-dependent signaling, and preclinical/clinical studies of NAD⁺ precursors was evaluated and organized into: (i) core biochemical functions in cellular energetics, (ii) NAD⁺ consumption in genome maintenance and immune signaling, and (iii) organ-focused evidence relevant to skin disorders, infertility and reproductive health, osteoarthritis, hearing loss, vision decline, gut barrier dysfunction, cardiovascular and renal metabolism, hepatic steatosis, neurological diseases, and skeletal muscle health.Results: NAD⁺ supports glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation, while acting as an essential substrate for PARP-driven DNA repair and sirtuin-mediated deacylation programs that shape mitochondrial fitness, inflammatory tone, and metabolic flexibility. Across experimental models, impaired NAD⁺ homeostasis repeatedly associates with mitochondrial dysfunction, heightened oxidative injury, and dysregulated immune–barrier responses, features shared by intestinal inflammation, neurodegeneration and ischemic injury, cardiometabolic disease, kidney injury, and fatty liver disease. Supplementation with NAD⁺ precursors (notably NR and NMN) reliably elevates NAD⁺ in preclinical systems and increases circulating NAD⁺ metabolites in humans, with early signals of pathway engagement; however, clinical outcomes remain heterogeneous across populations, dosing regimens, and endpoints. Evidence for intravenous NAD⁺ “drip” therapy is comparatively limited and insufficiently standardized, with constraints related to tolerability, dose consistency, and cost, underscoring the need for controlled trials.Conclusion: NAD⁺ occupies a central position at the interface of energy metabolism, genome integrity, and immunometabolic signaling, providing a coherent framework for understanding how cellular stress can propagate multisystem dysfunction. Although NAD⁺-boosting strategies are biologically plausible and mechanistically supported, definitive clinical benefit across skin, fertility, osteoarthritis, sensory decline, gut disorders, cardiovascular and hepatic disease, neurological conditions, and muscle health will require well-designed human studies with standardized biomarkers, safety surveillance, and clinically meaningful endpoints.
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Analysis and Control of a Glucose-insulin Dynamic Model

Published on: 1st March, 2026

The dynamics of the glucose-insulin regulatory system are highly nonlinear and must be understood to be controlled effectively. Bifurcation analysis and multiobjective nonlinear model predictive control (MNLMPC) are performed on a glucose-insulin dynamic model. MATCONT was used for the bifurcation analysis, and for the MNLMPC calculations, the optimization language PYOMO is used in conjunction with the solvers IPOPT and BARON. The bifurcation analysis revealed a Hopf bifurcation point and a limit point. A Hopf bifurcation point is a tipping point where a system that was behaving steadily suddenly starts to oscillate or cycle on its own, like a machine that begins to vibrate instead of staying still. A limit point is a tipping point at which pushing a system a little further suddenly causes it to jump to a completely different state, rather than changing smoothly. MNLMC converged on the Utopia solution. The Hopf bifurcation point, which leads to an unwanted limit cycle, is eliminated by an activation factor. A limit cycle is a repeating pattern of behavior that a system naturally settles into over time, like a steady heartbeat or a clock that keeps ticking. The limit point (which causes multiple steady-state solutions from a singular point enables the Multiobjective nonlinear model predictive control calculations to converge to the Utopia point (the best possible solution) in the model. A Utopia solution in multi-objective nonlinear model predictive control is an ideal operating point at which all goals are simultaneously perfectly optimized.
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