2,851
edits
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* Enhanced vulnerability of DNA to damage. | * Enhanced vulnerability of DNA to damage. | ||
* Increased susceptibility to age-related diseases such as diabetes, cardiovascular diseases, and neurodegenerative diseases. | * Increased susceptibility to age-related diseases such as diabetes, cardiovascular diseases, and neurodegenerative diseases. | ||
A gradual increase in CD38 has been implicated in the decline of [[wikipedia:NAD+|NAD+]] with age.<ref> | A gradual increase in CD38 has been implicated in the decline of [[wikipedia:NAD+|NAD+]] with age.<ref>Camacho-Pereira J, Tarragó MG, Chini CC, Nin V, Escande C, Warner GM, Puranik AS, Schoon RA, Reid JM, Galina A, Chini EN (June 2016). "CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism". ''Cell Metabolism''. '''23''' (6): 1127–1139. doi:10.1016/j.cmet.2016.05.006. PMC 4911708. PMID 27304511.</ref><ref>Schultz MB, Sinclair DA (June 2016). "Why NAD(+) Declines during Aging: It's Destroyed". ''Cell Metabolism''. '''23''' (6): 965–966. doi:10.1016/j.cmet.2016.05.022. PMC 5088772. PMID 27304496.</ref> Treatment of old mice with a specific CD38 inhibitor, [[wikipedia:CD38-IN-78c|78c]], prevents age-related NAD+ decline.<ref>Tarragó MG, Chini CC, Kanamori KS, Warner GM, Caride A, de Oliveira GC, Rud M, Samani A, Hein KZ, Huang R, Jurk D, Cho DS, Boslett JJ, Miller JD, Zweier JL, Passos JF, Doles JD, Becherer DJ, Chini EN (May 2018). "A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline". ''Cell Metabolism''. '''27''' (5): 1081–1095.e10. doi:10.1016/j.cmet.2018.03.016. PMC 5935140. PMID 29719225.</ref> CD38 [[wikipedia:Knockout_mouse|knockout mice]] have twice the levels of NAD+ and are resistant to age-associated NAD+ decline,<ref name="pmid32595066">Cambronne XA, Kraus WL (2020). "Location, Location, Location: Compartmentalization of NAD + Synthesis and Functions in Mammalian Cells". ''Trends in Biochemical Sciences''. '''45''' (10): 858–873. doi:10.1016/j.tibs.2020.05.010. PMC 7502477. PMID 32595066.</ref> with dramatically increased NAD+ levels in major organs (liver, muscle, brain, and heart).<ref name="pmid32594513">Kang BE, Choi J, Stein S, Ryu D (2020). "Implications of NAD + boosters in translational medicine". ''European Journal of Clinical Investigation''. '''50''' (10): e13334. doi:10.1111/eci.13334. PMID 32594513. S2CID 220254270.</ref> On the other hand, mice [[wikipedia:Gene_expression|overexpressing]] CD38 exhibit reduced NAD+ and [[wikipedia:Mitochondrial_disease|mitochondrial dysfunction]].<ref name="pmid32595066" /> | ||
=== Boosting NAD+ Levels === | === Boosting NAD+ Levels === |