CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels
Open accessAbstract
Decreased NAD+ levels have been shown to contribute to metabolic dysfunction during aging. NAD+ decline can be partially prevented by knockout of the enzyme CD38. However, it is not known how CD38 is regulated during aging, and how its ecto-enzymatic activity impacts NAD+ homeostasis. Here we show that an increase in CD38 in white adipose tissue (WAT) and the liver during aging is mediated by accumulation of CD38+ immune cells. Inflammation increases CD38 and decreases NAD+. In addition, senescent cells and their secreted signals promote accumulation of CD38+ cells in WAT, and ablation of senescent cells or their secretory phenotype decreases CD38, partially reversing NAD+ decline. Finally, blocking the ecto-enzymatic activity of CD38 can increase NAD+ through a nicotinamide mononucleotide (NMN)-dependent process. Our findings demonstrate that senescence-induced inflammation promotes accumulation of CD38 in immune cells that, through its ecto-enzymatic activity, decreases levels of NMN and NAD+.
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Senescent cells can decrease NAD+ via SASP activation of CD38 on macrophages, and senolytics partially restore tissue NAD+ levels.
“Senescent cells can decrease NAD+ through SASP activation of the NAD-degrading enzyme CD38 on the surface of macrophages and, remarkably, senolytics partially restore tissue NAD+ levels139,140.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [139]
The Results section on SASP-induced CD38 reports that secretions from senescent cells increased CD38 activity in macrophages and lowered NAD+ in mouse white adipose tissue. The Results section on cellular senescence reports that clearing senescent cells partly restored NAD+ in that tissue, but the experiment used genetic ablation in INK-ATTAC mice, not a senolytic treatment. The Discussion also notes that NAD+ recovery was much greater in the liver. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDuring ageing and obesity, SASP factors from senescent adipose cells upregulate CD38 in adipose immune cells, lowering NAD+ levels and worsening metabolic dysfunction and fitness.
“Upon ageing and obesity, SASP factors from the senescent cells upregulate CD38 in adipose immune cells, thereby decreasing NAD+ levels, which results in increased metabolic dysfunction and a decline in overall fitness127.”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [127]
The Results section, “Accumulation of CD38 in vivo can be induced by SASP” (page unavailable), reports that conditioned media from senescent pre-adipocytes increased macrophage CD38 and lowered NAD+ in mouse white adipose tissue. The Introduction links age-related NAD+ decline to metabolic dysfunction and reduced overall fitness. The paper does not establish this SASP–CD38 pathway in obesity or show that the pathway itself worsens metabolic function or fitness. (LLM, conf=0.87)
Experimental — accuracy not yet measuredChini and colleagues reported similar findings consistent with inflammaging as a driver of NAD decline during ageing.
“Chini and colleagues have reported similar findings, which are consistent with the role of inflammaging as a driver of NAD decline during ageing69.”
From Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages (2020) · cites this paper as [69]
CD38-overexpressing M1-like macrophages are activated directly by inflammatory cytokines secreted by senescent cells.
“these CD38-overexpressing M1-like macrophages are activated directly by inflammatory cytokines secreted by senescent cells (discussed in more detail later)45,105,106”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [105]
In ageing, declining NAD+ levels are associated with increased accumulation of proinflammatory M1-like resident macrophages in liver and fat, characterized by increased CD38 expression and heightened NADase activity.
“In ageing, declining NAD+ levels are associated with increased accumulation of proinflammatory M1-like resident macrophages in the liver and fat, which are characterized by increased expression of CD38 and heightened NADase activity45,105.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [105]
Innate immune cells, especially macrophages, may be the major cell population responding to the SASP with NAD+ degradation, thereby contributing to organism-wide decline in NAD+ levels.
“Recent observations suggest that innate immune cells, especially macrophages, may be the major cell population responding to the SASP with NAD+ degradation, thereby contributing to organism-wide decline in NAD+ levels45,105.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [105]
Senescent cells and their SASP activate CD38 expression and promote CD38-dependent NADase activity in macrophages.
“another group has also independently shown that senescent cells and their SASP activate CD38 expression and promote CD38-dependent NADase activity in macrophages105,106.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [105]
CD38 is emerging as a key enzyme involved in inflammageing and senescence, which are strongly associated with neurodegenerative diseases.
“CD38 is emerging as a key enzyme involved in inflammageing and senescence45,105,106, which are strongly associated with neurodegenerative diseases124,128,168,169.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [105]
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Cites
Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases
Franceschi, C., & Campisi, J. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu057 · Cited by 3,891 · see citing works
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · see citing works
Self-citationNaturally occurring antibodies devoid of light chains
Hamers-Casterman, C., Atarhouch, T., Muyldermans, S., Robinson, G., Hammers, C., Songa, E. B., Bendahman, N., & Hammers, R. (1993) · Nature · doi:10.1038/363446a0 · Cited by 3,241 · see citing works
Naturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,891 · see citing works
Self-citationRapid generation of functional human IgG antibodies derived from Fab-on-phage display libraries
Jostock, T., Vanhove, M., Brepoels, E., van Gool, R., Daukandt, M., Wehnert, A., van Hegelsom, R., Dransfield, D., Sexton, D., Devlin, M., et al. (2004) · Journal of Immunological Methods · doi:10.1016/j.jim.2004.03.014 · Cited by 2,562 · see citing works
Senolytics improve physical function and increase lifespan in old age
Xu, M., Pirtskhalava, T., Farr, J. N., Weigand, B. M., Palmer, A. K., Weivoda, M. M., Inman, C. L., Ogrodnik, M. B., Hachfeld, C. M., Fraser, D. G., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0092-9 · Cited by 2,287 · see citing works
Self-citationPersistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232 · see citing works
Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome
Yoshimoto, S., Loo, T. M., Atarashi, K., Kanda, H., Sato, S., Oyadomari, S., Iwakura, Y., Oshima, K., Morita, H., Hattori, M., et al. (2013) · Nature · doi:10.1038/nature12347 · Cited by 2,219 · see citing works
Engineered antibody fragments and the rise of single domains
Holliger, P., & Hudson, P. J. (2005) · Nature Biotechnology · doi:10.1038/nbt1142 · Cited by 1,928 · see citing works
Gomes, A. P., Price, N. L., Ling, A. J. Y., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.037 · Cited by 1,482 · see citing works
Yoshino, J., Mills, K. F., Yoon, M. J., & Imai, S.-I. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.014 · Cited by 1,340 · see citing works
Cellular senescence promotes adverse effects of chemotherapy and cancer relapse
Demaria, M., O'Leary, M. N., Chang, J., Shao, L., Liu, S., Alimirah, F., Koenig, K., Le, C., Mitin, N., Deal, A. M., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0241 · Cited by 1,338 · see citing works
Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype
Wiley, C. D., Velarde, M. C., Lecot, P., Liu, S., Sarnoski, E. A., Freund, A., Shirakawa, K., Lim, H. W., Davis, S. S., Ramanathan, A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.11.011 · Cited by 1,275 · see citing works
L1 drives IFN in senescent cells and promotes age-associated inflammation
De Cecco, M., Ito, T., Petrashen, A. P., Elias, A. E., Skvir, N. J., Criscione, S. W., Caligiana, A., Brocculi, G., Adney, E. M., Boeke, J. D., et al. (2019) · Nature · doi:10.1038/s41586-018-0784-9 · Cited by 1,255 · see citing works
Self-citationMouchiroud, L., Houtkooper, R. H., Moullan, N., Katsyuba, E., Ryu, D., Cantó, C., Mottis, A., Jo, Y.-S., Viswanathan, M., Schoonjans, K., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.016 · Cited by 1,210 · see citing works
Novel Markers to Delineate Murine M1 and M2 Macrophages
Jablonski, K., Amici, S. A., Webb, L., Ruiz‐Rosado, J. D. D., Popovich, P. G., Partida‐Sánchez, S., & Guerau‐de‐Arellano, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0145342 · Cited by 1,003 · see citing works
Xu, M., Tchkonia, T., Ding, H., Ogrodnik, M., Lubbers, E. R., Pirtskhalava, T., White, T. A., Johnson, K. O., Stout, M. B., Mezera, V., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1515386112 · Cited by 915 · see citing works
Self-citationCamacho-Pereira, J., Tarragó, M. G., Chini, C. C. S., Nin, V., Escande, C., Warner, G. M., Puranik, A. S., Schoon, R. A., Reid, J. M., Galina, A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.006 · Cited by 901 · see citing works
Self-citationEvolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology
Malavasi, F., Deaglio, S., Funaro, A., Ferrero, E., Horenstein, A. L., Ortolan, E., Vaisitti, T., & Aydin, S. (2008) · Physiological Reviews · doi:10.1152/physrev.00035.2007 · Cited by 862 · see citing works
NAD+ homeostasis in health and disease
Katsyuba, E., Romani, M., Hofer, D., & Auwerx, J. (2020) · Nature Metabolism · doi:10.1038/s42255-019-0161-5 · Cited by 627 · see citing works
Vitamin B <sub>3</sub> modulates mitochondrial vulnerability and prevents glaucoma in aged mice
Williams, P. A., Harder, J. M., Foxworth, N. E., Cochran, K. E., Philip, V. M., Porciatti, V., Smithies, O., & John, S. W. M. (2017) · Science · doi:10.1126/science.aal0092 · Cited by 617 · see citing works
Modulation of mammalian life span by the short isoform of p53
Maier, B., Gluba, W., Bernier, B., Turner, T., Mohammad, K., Guise, T., Sutherland, A., Thorner, M., & Scrable, H. (2004) · Genes & Development · doi:10.1101/gad.1162404 · Cited by 586 · see citing works
Quantitative Analysis of NAD Synthesis-Breakdown Fluxes
Liu, L., Su, X., Quinn, W. J., Hui, S., Krukenberg, K., Frederick, D. W., Redpath, P., Zhan, L., Chellappa, K., White, E., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.018 · Cited by 564 · see citing works
Self-citationSingle domain antibodies: promising experimental and therapeutic tools in infection and immunity
Wesolowski, J., Alzogaray, V., Reyelt, J., Unger, M., Juárez‐Moreno, K., Urrutia, M., Cauerhff, A., Danquah, W., Rissiek, B., Scheuplein, F., et al. (2009) · Medical Microbiology and Immunology · doi:10.1007/s00430-009-0116-7 · Cited by 516 · see citing works
Macrophage de novo NAD+ synthesis specifies immune function in aging and inflammation
Minhas, P. S., Liu, L., Moon, P. K., Joshi, A. U., Dove, C., Mhatre, S., Contrepois, K., Wang, Q., Lee, B. A., Coronado, M., et al. (2019) · Nature Immunology · doi:10.1038/s41590-018-0255-3 · Cited by 501 · see citing works
Self-citationCD38 antibodies in multiple myeloma: back to the future
van de Donk, N. W. C. J., Richardson, P. G. G., & Malavasi, F. (2017) · Blood · doi:10.1182/blood-2017-06-740944 · Cited by 495 · see citing works
Potent enzyme inhibitors derived from dromedary heavy‐chain antibodies
Lauwereys, M., Ghahroudi, M. A., Desmyter, A., Kinne, J., Hölzer, W., Genst, E. D., Wyns, L., & Muyldermans, S. (1998) · The EMBO Journal · doi:10.1093/emboj/17.13.3512 · Cited by 492 · see citing works
Partida-Sánchez, S., Cockayne, D. A., Monard, S., Jacobson, E. L., Oppenheimer, N., Garvy, B., Kusser, K., Goodrich, S., Howard, M., Harmsen, A., et al. (2001) · Nature Medicine · doi:10.1038/nm1101-1209 · Cited by 450 · see citing works
Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages
Covarrubias, A. J., Kale, A., Perrone, R., Lopez-Dominguez, J. A., Pisco, A. O., Kasler, H. G., Schmidt, M. S., Heckenbach, I., Kwok, R., Wiley, C. D., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00305-3 · Cited by 420 · see citing works
Extracellular vesicle-contained eNAMPT delays aging and extends lifespan in mice
Yoshida, M., Satoh, A., Lin, J. B., Mills, K. F., Sasaki, Y., Rensing, N., Wong, M., Apte, R. S., & Imai, S.-I. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.05.015 · Cited by 407 · see citing works
Quantitative identification of senescent cells in aging and disease
Biran, A., Zada, L., Abou Karam, P., Vadai, E., Roitman, L., Ovadya, Y., Porat, Z., & Krizhanovsky, V. (2017) · Aging Cell · doi:10.1111/acel.12592 · Cited by 402 · see citing works
Picciotto, N. E., Gano, L. B., Johnson, L. C., Martens, C. R., Sindler, A. L., Mills, K. F., Imai, S., & Seals, D. R. (2016) · Aging Cell · doi:10.1111/acel.12461 · Cited by 396 · see citing works
Tarragó, M. G., Chini, C. C. S., Kanamori, K. S., Warner, G. M., Caride, A., de Oliveira, G. C., Rud, M., Samani, A., Hein, K. Z., Huang, R., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.016 · Cited by 384 · see citing works
Self-citationRegulation of intracellular levels of NAD: A novel role for CD38
Aksoy, P., White, T. A., Thompson, M., & Chini, E. N. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.05.042 · Cited by 353 · see citing works
Self-citationA high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in Cockayne syndrome
Scheibye-Knudsen, M., Mitchell, S. J., Fang, E. F., Iyama, T., Ward, T., Wang, J., Dunn, C. A., Singh, N., Veith, S., Hasan-Olive, M. M., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.10.005 · Cited by 352 · see citing works
Babu, J. R., Jeganathan, K. B., Baker, D. J., Wu, X., Kang, N., & van Deursen, J. M. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200211048 · Cited by 342 · see citing works
Self-citationThe Multi-faceted Ecto-enzyme CD38: Roles in Immunomodulation, Cancer, Aging, and Metabolic Diseases
Hogan, K. A., Chini, C. C. S., & Chini, E. N. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01187 · Cited by 337 · see citing works
Self-citationDeckert, J., Wetzel, M.-C., Bartle, L. M., Skaletskaya, A., Goldmacher, V. S., Vallée, F., Zhou-Liu, Q., Ferrari, P., Pouzieux, S., Lahoute, C., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0695 · Cited by 333 · see citing works
Lumeng, C. N., Liu, J., Geletka, L., Delaney, C., Delproposto, J., Desai, A., Oatmen, K., Martinez-Santibanez, G., Julius, A., Garg, S., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1102188 · Cited by 328 · see citing works
Slc12a8 is a nicotinamide mononucleotide transporter
Grozio, A., Mills, K. F., Yoshino, J., Bruzzone, S., Sociali, G., Tokizane, K., Lei, H. C., Cunningham, R., Sasaki, Y., Migaud, M. E., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-018-0009-4 · Cited by 287 · see citing works
Detalle, L., Stöhr, T., Palomo, C., Piedra, P. A., Gilbert, B. E., Más, V., Millar, A., Power, U. F., Stortelers, C., Allosery, K., et al. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01802-15 · Cited by 279 · see citing works
CD38-NAD+Axis Regulates Immunotherapeutic Anti-Tumor T Cell Response
Chatterjee, S., Daenthanasanmak, A., Chakraborty, P., Wyatt, M. W., Dhar, P., Selvam, S. P., Fu, J., Zhang, J., Nguyen, H., Kang, I., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.10.006 · Cited by 270 · see citing works
Stein, L. R., & Imai, S. (2014) · The EMBO Journal · doi:10.1002/embj.201386917 · Cited by 265 · see citing works
Guan, Y., Wang, S.-R., Huang, X.-Z., Xie, Q.-H., Xu, Y.-Y., Shang, D., & Hao, C.-M. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2016040385 · Cited by 238 · see citing works
Camelid and shark single domain antibodies: Structural features and therapeutic potential
Könning, D., Zielonka, S., Grzeschik, J., Empting, M., Valldorf, B., Krah, S., Schröter, C., Sellmann, C., Hock, B., & Kolmar, H. (2017) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2016.10.019 · Cited by 214 · see citing works
Gut microbiota lipopolysaccharide accelerates inflamm-aging in mice
Kim, K.-A., Jeong, J.-J., Yoo, S.-Y., & Kim, D.-H. (2016) · BMC Microbiology · doi:10.1186/s12866-016-0625-7 · Cited by 196 · see citing works
A conserved NAD + binding pocket that regulates protein-protein interactions during aging
Li, J., Bonkowski, M. S., Moniot, S., Zhang, D., Hubbard, B. P., Ling, A. J. Y., Rajman, L. A., Qin, B., Lou, Z., Gorbunova, V. A., et al. (2017) · Science · doi:10.1126/science.aad8242 · Cited by 188 · see citing works
NAD+ biosynthesis, aging, and disease
Johnson, S., & Imai, S. (2018) · F1000Research · doi:10.12688/f1000research.12120.1 · Cited by 178 · see citing works
The Membrane-Bound Enzyme CD38 Exists in Two Opposing Orientations
Zhao, Y. J., Lam, C. M. C., & Lee, H. C. (2012) · Science Signaling · doi:10.1126/scisignal.2002700 · Cited by 173 · see citing works
Aksoy, P., Escande, C., White, T. A., Thompson, M., Soares, S. M., Benech, J. C., & Chini, E. N. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.08.066 · Cited by 173 · see citing works
Self-citationMcReynolds, M. R., Chellappa, K., & Baur, J. A. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.110888 · Cited by 169 · see citing works
Self-citationGrozio, A., Sociali, G., Sturla, L., Caffa, I., Soncini, D., Salis, A., Raffaelli, N., De Flora, A., Nencioni, A., & Bruzzone, S. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.470435 · Cited by 158 · see citing works
Vafa, O., Gilliland, G. L., Brezski, R. J., Strake, B., Wilkinson, T., Lacy, E. R., Scallon, B. J., Teplyakov, A., Malia, T., & Strohl, W. R. (2013) · Methods · doi:10.1016/j.ymeth.2013.06.035 · Cited by 154 · see citing works
Elevated Muscle TLR4 Expression and Metabolic Endotoxemia in Human Aging
Ghosh, S., Lertwattanarak, R., Garduno, J. D. J., Galeana, J. J., Li, J., Zamarripa, F., Lancaster, J. L., Mohan, S., Hussey, S., & Musi, N. (2015) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu067 · Cited by 150 · see citing works
Whole Chromosome Instability induces senescence and promotes SASP
Andriani, G. A., Almeida, V. P., Faggioli, F., Mauro, M., Tsai, W. L., Santambrogio, L., Maslov, A. Y., Gadina, M., Campisi, J., Vijg, J., et al. (2016) · Scientific Reports · doi:10.1038/srep35218 · Cited by 146 · see citing works
Chini, C., Hogan, K. A., Warner, G. M., Tarragó, M. G., Peclat, T. R., Tchkonia, T., Kirkland, J. L., & Chini, E. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.03.199 · Cited by 138 · see citing works
Self-citationNAD+-Metabolizing Ectoenzymes in Remodeling Tumor–Host Interactions: The Human Myeloma Model
Horenstein, A. L., Chillemi, A., Quarona, V., Zito, A., Roato, I., Morandi, F., Marimpietri, D., Bolzoni, M., Toscani, D., Oldham, R. J., et al. (2015) · Cells · doi:10.3390/cells4030520 · Cited by 113 · see citing works
Matalonga, J., Glaría, E., Bresque, M., Escande, C., Carbó, J. M., Kiefer, K., Vicente, R., León, T., Beceiro, S., Pascual-García, M., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.01.007 · Cited by 109 · see citing works
Self-citationHorenstein, A. L., Quarona, V., Toscani, D., Costa, F., Chillemi, A., Pistoia, V., Giuliani, N., & Malavasi, F. (2016) · Molecular Medicine · doi:10.2119/molmed.2016.00198 · Cited by 99 · see citing works
Yoshino, J., & Imai, S. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-637-5_14 · Cited by 95 · see citing works
Lymphoid neogenesis and immune infiltration in aged liver
Singh, P., Coskun, Z. Z., Goode, C., Dean, A. M., Thompson-Snipes, L., & Darlington, G. (2008) · Hepatology · doi:10.1002/hep.22224 · Cited by 95 · see citing works
Funaro, A., Horenstein, A. L., Calosso, L., Morra, M., Tarocco, R. P., Franco, L., FLORA, A. D., & Malavasi, F. (1996) · International Immunology · doi:10.1093/intimm/8.11.1643 · Cited by 88 · see citing works
Aging, Depot Origin, and Preadipocyte Gene Expression
Cartwright, M. J., Schlauch, K. A., Lenburg, M. E., Tchkonia, T., Pirtskhalava, T., Cartwright, A., Thomou, T., & Kirkland, J. L. (2010) · The Journals of Gerontology Series A · doi:10.1093/gerona/glp213 · Cited by 87 · see citing works
Self-citationOsborn, M. J., Ma, B., Avis, S., Binnie, A., Dilley, J., Yang, X., Lindquist, K. C., Ménoret, S., Iscache, A.-L., Ouisse, L., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203041 · Cited by 86 · see citing works
The CD38/cyclic ADP-ribose system: A topological paradox
FLORA, A. D., Guida, L., Franco, L., & Zocchi, E. (1997) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(97)00062-9 · Cited by 82 · see citing works
Emerging Functions of Extracellular Pyridine Nucleotides
Billington, R. A., Bruzzone, S., FLORA, A. D., Genazzani, A. A., Koch‐Nolte, F., Ziegler, M., & Zocchi, E. (2006) · Molecular Medicine · doi:10.2119/2006-00075.billington · Cited by 76 · see citing works
Yuan, Y. J., Li, J., Zhu, X., Tang, X., Bao, Y., Sun, X., Huang, Y., Tian, F., Liu, X., & Yang, L. (2017) · International Journal of Nanomedicine · doi:10.2147/ijn.s127575 · Cited by 69 · see citing works
Sun, L., Adebanjo, O. A., Koval, A. P., Anandatheerthavarada, H. K., Iqbal, J. Z., Wu, X. Y., Moonga, B. S., Wu, X. B., Biswas, G., Bevis, P. J. R., et al. (2002) · The FASEB Journal · doi:10.1096/fj.01-0705com · Cited by 64 · see citing works
Liu, L., Ke, Y., Jiang, X. Y., He, F., Pan, L., Xu, L., Zeng, X., & Ba, X. (2012) · Human Immunology · doi:10.1016/j.humimm.2012.02.002 · Cited by 60 · see citing works
Emerging functions of extracellular pyridine nucleotides.
Billington, R., Bruzzone, S., FLORA, A. D., et al. (2007) · PubMed · doi:10.2119/2006–00075.billington · Cited by 58 · see citing works
Johnson, S., Wozniak, D. F., & Imai, S. (2018) · npj Aging and Mechanisms of Disease · doi:10.1038/s41514-018-0029-z · Cited by 57 · see citing works
Becherer, J. D., Boros, E. E., Carpenter, T. Y., Cowan, D. J., Deaton, D. N., Haffner, C. D., Jeune, M. R., Kaldor, I. W., Poole, J. C., Preugschat, F., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00992 · Cited by 55 · see citing works
Synthesis of NAADP and cADPR in Mitochondria
Liang, M., Chini, E. N., Cheng, J., & Dousa, T. P. (1999) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1999.1463 · Cited by 53 · see citing works
Self-citationNext generation immunotherapeutics—honing the magic bullet
Enever, C., Batuwangala, T. D., Plummer, C., & Sepp, A. (2009) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2009.07.002 · Cited by 49 · see citing works
Cohen, C., Mouterde, T., Quéré, D., & Clanet, C. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1419315112 · Cited by 40 · see citing works
Boslett, J. J., Helal, M., Chini, E. N., & Zweier, J. L. (2018) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2018.02.015 · Cited by 39 · see citing works
Self-citationda Silva, C. P., Schweitzer, K., Heyer, P., Malavasi, F., Mayr, G. W., & Guse, A. H. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)01396-9 · Cited by 37 · see citing works
CD38 is methylated in prostate cancer and regulates extracellular NAD+
Mottahedeh, J., Haffner, M. C., Grogan, T., Hashimoto, T., Crowell, P. D., Beltran, H., Sboner, A., Bareja, R., Esopi, D., Isaacs, W. B., et al. (2018) · Cancer & Metabolism · doi:10.1186/s40170-018-0186-3 · Cited by 36 · see citing works
Zielinska, W., Barata, H., & Chini, E. N. (2003) · Life Sciences · doi:10.1016/j.lfs.2003.08.033 · Cited by 34 · see citing works
Self-citationLipopolysaccharide Induces CD38 Expression and Solubilization in J774 Macrophage Cells
Lee, C.-U., Song, E., Yoo, C.-H., Kwak, Y.-K., & Han, M. (2012) · Molecules and Cells · doi:10.1007/s10059-012-0263-3 · Cited by 32 · see citing works
Brezis, M., Rosen, S., Stoff, J. S., Spokes, K., Silva, P., & Epstein, F. H. (1986) · PubMed · Cited by 31 · see citing works
A pre-steady state and steady state kinetic analysis of the N-ribosyl hydrolase activity of hCD157
Preugschat, F., Carter, L. H., Boros, E. E., Porter, D. J. T., Stewart, E. L., & Shewchuk, L. M. (2014) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2014.09.008 · Cited by 29 · see citing works
Harris, K. E., Aldred, S. F., Davison, L. M., Ogana, H. A. N., Boudreau, A. A., Brüggemann, M., Osborn, M. J., Ma, B., Buelow, B., Clarke, S., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00889 · Cited by 28 · see citing works
Self-citationBAPS collective review chronic inflammatory bowel disease
Raine, P. A. M. (1984) · Journal of Pediatric Surgery · doi:10.1016/s0022-3468(84)80008-1 · Cited by 22 · see citing works
Relationship of Bile Salts and Bile Flow to Biliary Excretion of Iopanoic Acid
Moss, A. A., Amberg, J. R., & Jones, S. R. (1972) · Investigative Radiology · doi:10.1097/00004424-197201000-00002 · Cited by 16 · see citing works
Phase II study of AMSA in refractory testicular cancer.
Sd, W., Duncan, P. W., & Einhorn, L. H. (1983) · PubMed · Cited by 7 · see citing works
Dzhoraev, I. G. (1988) · PubMed · Cited by 2 · see citing works
Wb, S. (1974) · PubMed · Cited by 2 · see citing works
van Welsum, R. A. (1970) · PubMed · Cited by 1 · see citing works
[Structural organization of the pneumococcal bacterial cell].
Ln, P. (1985) · PubMed · Cited by 1 · see citing works
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NAD+ metabolism and its roles in cellular processes during ageing
Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00313-x · Cited by 1,617 · see citing works
Cellular senescence and senolytics: the path to the clinic
Chaib, S., Tchkonia, T., & Kirkland, J. L. (2022) · Nature Medicine · doi:10.1038/s41591-022-01923-y · Cited by 1,105 · see citing works
Self-citationMitochondrial dysfunction in cell senescence and aging
Miwa, S., Kashyap, S., Chini, E., & von Zglinicki, T. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158447 · Cited by 1,061 · see citing works
Self-citationThe metabolic roots of senescence: mechanisms and opportunities for intervention
Wiley, C. D., & Campisi, J. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00483-8 · Cited by 691 · see citing works
Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages
Covarrubias, A. J., Kale, A., Perrone, R., Lopez-Dominguez, J. A., Pisco, A. O., Kasler, H. G., Schmidt, M. S., Heckenbach, I., Kwok, R., Wiley, C. D., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00305-3 · Cited by 420 · see citing works
SenNet recommendations for detecting senescent cells in different tissues
Suryadevara, V., Hudgins, A. D., Rajesh, A., Pappalardo, A., Karpova, A., Dey, A. K., Hertzel, A., Agudelo, A., Rocha, A., Soygur, B., et al. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00738-8 · Cited by 408 · see citing works
“Upon ageing and obesity, SASP factors from the senescent cells upregulate CD38 in adipose immune cells, thereby decreasing NAD + levels, which results in increased metabolic dysfunction and a decline in over-all fitness 127 .”
Self-citationImmune ageing at single-cell resolution
Mogilenko, D. A., Shchukina, I., & Artyomov, M. N. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00646-4 · Cited by 392 · see citing works
Bao, H., Cao, J., Chen, M., Min, C., Chen, W., Chen, X., Chen, Y., Chen, Y., Chen, Y., Chen, Z., et al. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2305-0 · Cited by 389 · see citing works
Metabolites as signalling molecules
Baker, S. A., & Rutter, J. P. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00572-w · Cited by 376 · see citing works
Cellular senescence: all roads lead to mitochondria
Martini, H., & Passos, J. F. (2023) · The FEBS Journal · doi:10.1111/febs.16361 · Cited by 334 · see citing works
Evolving concepts in NAD+ metabolism
Chini, C. C. S., Zeidler, J. D., Kashyap, S., Warner, G. M., & Chini, E. N. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.04.003 · Cited by 294 · see citing works
Self-citationInflammation: the incubator of the tumor microenvironment
Denk, D., & Greten, F. R. (2022) · Trends in cancer · doi:10.1016/j.trecan.2022.07.002 · Cited by 279 · see citing works
NAD + Metabolism in Cardiac Health, Aging, and Disease
Abdellatif, M., Sedej, S., & Kroemer, G. (2021) · Circulation · doi:10.1161/circulationaha.121.056589 · Cited by 262 · see citing works
Pleiotropic effects of mitochondria in aging
de Lima, T. I., Li, T. Y., Mottis, A., & Auwerx, J. H. (2022) · Nature Aging · doi:10.1038/s43587-022-00191-2 · Cited by 242 · see citing works
Human skeletal muscle aging atlas
Kedlian, V. R., Wang, Y., Liu, T., Chen, X., Bolt, L., Tudor, C., Shen, Z., Fasouli, E. S., Prigmore, E., Kleshchevnikov, V., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00613-3 · Cited by 218 · see citing works
Inflammation and DNA damage: cause, effect or both
Pezone, A., Olivieri, F., Napoli, M. V., Procopio, A., Avvedimento, E. V., & Gabrielli, A. (2023) · Nature Reviews Rheumatology · doi:10.1038/s41584-022-00905-1 · Cited by 212 · see citing works
Critical Role of the cGAS-STING Pathway in Doxorubicin-Induced Cardiotoxicity
Luo, W., Zou, X., Wang, Y., Dong, Z., Weng, X., Pei, Z., Song, S., Zhao, Y., Wei, Z., Gao, R., et al. (2023) · Circulation Research · doi:10.1161/circresaha.122.321587 · Cited by 182 · see citing works
Cellular senescence in knee osteoarthritis: molecular mechanisms and therapeutic implications
Xie, J., Wang, Y., Lu, L., Liu, L., Yu, X., & Pei, F. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101413 · Cited by 174 · see citing works
NAD metabolism: Role in senescence regulation and aging
Chini, C. C. S., Cordeiro, H. S., Tran, N. L. K., & Chini, E. N. (2023) · Aging Cell · doi:10.1111/acel.13920 · Cited by 138 · see citing works
Self-citationRegulation of and challenges in targeting NAD+ metabolism
Migaud, M. E., Ziegler, M., & Baur, J. A. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00752-w · Cited by 139 · see citing works
Self-citationRole of Cellular Senescence in Type II Diabetes
Narasimhan, A., Flores, R. R., Robbins, P. D., & Niedernhofer, L. J. (2021) · Endocrinology · doi:10.1210/endocr/bqab136 · Cited by 133 · see citing works
NAD+ flux is maintained in aged mice despite lower tissue concentrations
McReynolds, M. R., Chellappa, K., Chiles, E., Jankowski, C., Shen, Y., Chen, L., Descamps, H. C., Mukherjee, S., Bhat, Y. R., Lingala, S. R., et al. (2021) · Cell Systems · doi:10.1016/j.cels.2021.09.001 · Cited by 112 · see citing works
Self-citationRegulation of NAD+ metabolism in aging and disease
Chu, X., & Raju, R. P. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154923 · Cited by 106 · see citing works
NADase CD38 is a key determinant of ovarian aging
Yang, Q., Chen, W., Cong, L., Wang, M., Li, H., Wang, H., Luo, X., Zhu, J., Zeng, X., Zhu, Z., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00532-9 · Cited by 104 · see citing works
Yang, L., Shen, J., Liu, C., Kuang, Z., Tang, Y., Qian, Z., Guan, M., Yang, Y., Zhan, Y., Li, N., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36543-8 · Cited by 102 · see citing works
Strategies for late phase preclinical and early clinical trials of senolytics
Gerdes, E. O. W., Misra, A., Espíndola‐Netto, J. M., Tchkonia, T., & Kirkland, J. L. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111591 · Cited by 101 · see citing works
Self-citationRoboon, J., Hattori, T., Ishii, H., Takarada‐Iemata, M., Nguyen, D. T., Heer, C. D., O’Meally, D., Brenner, C., Yamamoto, Y., Okamoto, H., et al. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15367 · Cited by 93 · see citing works
The CD38 glycohydrolase and the NAD sink: implications for pathological conditions
Zeidler, J. D., Hogan, K. A., Agorrody, G., Peclat, T., Kashyap, S., Kanamori, K. S., Gomez, L. S., Mazdeh, D. Z., Warner, G. M., Thompson, K. L., et al. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00451.2021 · Cited by 90 · see citing works
Self-citationGan, L., Liu, D., Liu, J., Chen, E., Chen, C., Liu, L., Hu, H., Guan, X., Ma, W., Zhang, Y., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00625-0 · Cited by 87 · see citing works
The intestinal immune system and gut barrier function in obesity and ageing
Shemtov, S. J., Emani, R., Bielska, O., Covarrubias, A. J., Verdin, E. M., Andersen, J. K., & Winer, D. A. (2022) · FEBS Journal · doi:10.1111/febs.16558 · Cited by 83 · see citing works
Li, N., Li, Y., Hu, J., Wu, Y., Yang, J., Fan, H., Li, L., Luo, D., Ye, Y., Gao, Y., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.845209 · Cited by 79 · see citing works
Targeting Cell Senescence and Senolytics: Novel Interventions for Age-Related Endocrine Dysfunction
Suda, M., Paul, K. H., Tripathi, U., Minamino, T., Tchkonia, T., & Kirkland, J. L. (2024) · Endocrine Reviews · doi:10.1210/endrev/bnae010 · Cited by 81 · see citing works
Self-citationLiu, G., Jiang, C., Lin, X., & Yang, Y. (2021) · Open Research (University of Surrey) · doi:10.1002/viw.20210003 · Cited by 77 · see citing works
Bratkowski, M. A., Burdett, T. C., Danao, J., Wang, X., Mathur, P., Gu, W., Beckstead, J. A., Talreja, S., Yang, Y.-S., Danko, G., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.08.017 · Cited by 77 · see citing works
BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities
Yaku, K., Palikhe, S., Izumi, H., Yoshida, T., Hikosaka, K., Hayat, F., Karim, M., Iqbal, T., Nitta, Y., Sato, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-27080-3 · Cited by 76 · see citing works
Osteoarthritis year in review 2023: Biology
Roelofs, A. J., & Bari, C. D. (2023) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2023.11.002 · Cited by 76 · see citing works
A multimodal atlas of tumour metabolism reveals the architecture of gene–metabolite covariation
Benedetti, E., Liu, E. M., Tang, C., Kuo, F., Büyüközkan, M., Park, T., Park, J., Correa, F., Hakimi, A. A., Intlekofer, A. M., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00817-8 · Cited by 76 · see citing works
Targeting CD38-dependent NAD+ metabolism to mitigate multiple organ fibrosis
Shi, B., Wang, W., Korman, B. D., Li, K., Wang, Q., Wei, J., Bale, S., Marangoni, R. G., Bhattacharyya, S., Miller, S. D., et al. (2020) · iScience · doi:10.1016/j.isci.2020.101902 · Cited by 72 · see citing works
Self-citationNicotinamide adenine dinucleotide metabolism in the immune response, autoimmunity and inflammageing
Navarro, M. N., Heras, M. M. G. D. L., & Mittelbrunn, M. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15477 · Cited by 70 · see citing works
CD38 Mediates Lung Fibrosis by Promoting Alveolar Epithelial Cell Aging
Cui, H., Xie, N., Banerjee, S., Dey, T., Liu, R.-M., Antony, V. B., Sanders, Y. Y., Adams, T. S., Gómez, J. L., Thannickal, V. J., et al. (2022) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202109-2151oc · Cited by 70 · see citing works
Qiu, Y.-M., Xu, S., Chen, X., Wu, X., Zhou, Z., Zhang, J.-N., Tu, Q., Dong, B., Liu, Z.-F., He, J., et al. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01577-3 · Cited by 58 · see citing works
Long, Y., Yang, B., Lei, Q., Gao, F., Chen, L., Chen, W., Chen, S., Ren, W., Cao, Y., Xu, L., et al. (2024) · ACS Nano · doi:10.1021/acsnano.3c10547 · Cited by 65 · see citing works
The balance between NAD+ biosynthesis and consumption in ageing
Strømland, Ø., Diab, J., Ferrario, E., Sverkeli, L. J., & Ziegler, M. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111569 · Cited by 63 · see citing works
Sharma, A., Chabloz, S., Lapides, R. A., Roider, E., & Ewald, C. Y. (2023) · Nutrients · doi:10.3390/nu15020445 · Cited by 60 · see citing works
Inflammatory Mechanisms in Heart Failure with Preserved Ejection Fraction
Daou, D., Gillette, T. G., & Hill, J. A. (2023) · Physiology · doi:10.1152/physiol.00004.2023 · Cited by 74 · see citing works
Boháčová, P., Terekhova, M., Tsurinov, P., Mullins, R. D. Z., Husarcikova, K., Shchukina, I., Antonova, A. U., Echalar, B., Kössl, J., Saidu, A., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.08.019 · Cited by 62 · see citing works
Terao, R., Lee, T. J., Colasanti, J. J., Pfeifer, C. W., Lin, J. B., Santeford, A. C., Hase, K., Yamaguchi, S., Du, D., Sohn, B. S., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114102 · Cited by 59 · see citing works
Huang, Y., Shao, M., Teng, X., Si, X., Wu, L., Jiang, P., Liu, L., Cai, B., Wang, X., Han, Y., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101400 · Cited by 58 · see citing works
Mitochondria during T cell aging
Escrig-Larena, J. I., Delgado-Pulido, S., & Mittelbrunn, M. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101808 · Cited by 58 · see citing works
Impact of NAD+ metabolism on ovarian aging
Liang, J., Huang, F., Song, Z., Tang, R., Zhang, P., & Chen, R. (2023) · Immunity & Ageing · doi:10.1186/s12979-023-00398-w · Cited by 56 · see citing works
Sun, X., & Feinberg, M. W. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.693067 · Cited by 55 · see citing works
Immunometabolism: signaling pathways, homeostasis, and therapeutic targets
Xu, R., He, X., Xu, J., Yu, G., & Wu, Y. (2024) · MedComm · doi:10.1002/mco2.789 · Cited by 55 · see citing works
CD38 in the age of COVID-19: a medical perspective
Horenstein, A., Faini, A., & Malavasi, F. (2021) · Physiological Reviews · doi:10.1152/physrev.00046.2020 · Cited by 53 · see citing works
NAD+ metabolism-based immunoregulation and therapeutic potential
Fang, J., Chen, W., Hou, P., Liu, Z., Zuo, M., Liu, S., Feng, C., Han, Y., Li, P., Shi, Y., et al. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01031-5 · Cited by 54 · see citing works
CD38 inhibitor 78c increases mice lifespan and healthspan in a model of chronological aging
Peclat, T., Thompson, K. L., Warner, G. M., Chini, C. C. S., Tarragó, M. G., Mazdeh, D. Z., Zhang, C., Zavala‐Solorio, J., Kolumam, G. A., Wong, Y. L., et al. (2022) · Aging Cell · doi:10.1111/acel.13589 · Cited by 52 · see citing works
Self-citationYang, F., Wang, X., Yang, D., Lu, Y., Wei, G., Yu, W., Liu, X., Zheng, Q., Ying, J., & Hua, F. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.738686 · Cited by 50 · see citing works
Emerging strategies, applications and challenges of targeting NAD+ in the clinic
Zhang, J., Wang, H., Lautrup, S., Nilsen, H. L., Treebak, J. T., Watne, L. O., Selbæk, G., Wu, L. E., Omland, T., Pirinen, E., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00947-6 · Cited by 58 · see citing works
Roles of NAD+ in Acute and Chronic Kidney Diseases
Morevati, M., Fang, E. F., Mace, M. L., Kanbay, M., Gravesen, E., Nordholm, A., Egstrand, S., & Hornum, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010137 · Cited by 49 · see citing works
Pharmacology and Potential Implications of Nicotinamide Adenine Dinucleotide Precursors
She, J., Sheng, R., & Qin, Z. (2021) · Aging and Disease · doi:10.14336/ad.2021.0523 · Cited by 49 · see citing works
Long‐Term Nicotinamide Riboside Use Improves Coordination and Eye Movements in Ataxia Telangiectasia
Presterud, R., Deng, W. H., Wennerström, A. B., Burgers, T., Gajera, B., Mattsson, K., Solberg, A., Fang, E. F., Nieminen, A. I., Stray‐Pedersen, A., et al. (2023) · Movement Disorders · doi:10.1002/mds.29645 · Cited by 46 · see citing works
Age-associated nicotinamide adenine dinucleotide decline drives CAR-T cell failure
Hope, H. C., de Sostoa, J., Ginefra, P., Andreatta, M., Chiang, Y.-H., Ronet, C., Pich-Bavastro, C., Corría-Osorio, J., Kuonen, F., Auwerx, J. H., et al. (2025) · Nature Cancer · doi:10.1038/s43018-025-00982-7 · Cited by 46 · see citing works
A Novel NAD Signaling Mechanism in Axon Degeneration and its Relationship to Innate Immunity
Hopkins, E. L., Gu, W., Kobe, B., & Coleman, M. P. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.703532 · Cited by 46 · see citing works
Zhang, X., He, T., Wu, Z., Wang, Y., Liu, H., Zhang, B., Yang, S., Wang, D., Huang, C., Duan, J., et al. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.09.026 · Cited by 46 · see citing works
T-Cell Senescence in Human Metabolic Diseases
Nga, H. T., Nguyen, T. L., & Yi, H. (2024) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2024.0140 · Cited by 46 · see citing works
NAD+ Metabolism and Immune Regulation: New Approaches to Inflammatory Bowel Disease Therapies
Chen, C., Yan, W., Tao, M., & Fu, Y. (2023) · Antioxidants · doi:10.3390/antiox12061230 · Cited by 44 · see citing works
Nicotinamide Adenine Dinucleotide in Aging Biology: Potential Applications and Many Unknowns
Bhasin, S., Seals, D. R., Migaud, M. E., Musi, N., & Baur, J. A. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad019 · Cited by 47 · see citing works
Self-citationChen, Y., Chen, L., Wu, X., Zhao, Y., Wang, Y., Jiang, D., Liu, X., Zhou, T., Li, S., Wei, Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37247-9 · Cited by 43 · see citing works
Metabolic reprogramming: a bridge between aging and tumorigenesis
Drapela, S., Ilter, D., & Gomes, A. P. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13261 · Cited by 41 · see citing works
Balancing NAD+ deficits with nicotinamide riboside: therapeutic possibilities and limitations
Cercillieux, A., Ciarlo, E., & Cantó, C. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04499-5 · Cited by 41 · see citing works
NAD+ Metabolism, Metabolic Stress, and Infection
Groth, B., Venkatakrishnan, P., & Lin, S.-J. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.686412 · Cited by 41 · see citing works
Tokizane, K., Brace, C. S., & Imai, S. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2023.12.011 · Cited by 40 · see citing works
Role of senescence in the chronic health consequences of COVID-19
Wissler Gerdes, E. O., Vanichkachorn, G., Verdoorn, B. P., Hanson, G. J., Joshi, A. Y., Murad, M. H., Rizza, S. A., Hurt, R. T., Tchkonia, T., & Kirkland, J. L. (2022) · Translational Research · doi:10.1016/j.trsl.2021.10.003 · Cited by 38 · see citing works
Self-citationThe central role of DNA damage in immunosenescence
Kell, L., Simon, A. K., Alsaleh, G., & Cox, L. S. (2023) · Frontiers in Aging · doi:10.3389/fragi.2023.1202152 · Cited by 38 · see citing works
The Key Role of NAD+ in Anti-Tumor Immune Response: An Update
Morandi, F., Horenstein, A. L., & Malavasi, F. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.658263 · Cited by 37 · see citing works
Targeting NAD+ metabolism: dual roles in cancer treatment
Yong, J., Cai, S., & Zeng, Z.-L. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1269896 · Cited by 36 · see citing works
Senescent Cells Accumulate in Systemic Sclerosis Skin
Shi, B., Tsou, P., Ma, F., Mariani, M., Mattichak, M. N., LeBrasseur, N. K., Chini, E. N., Lafyatis, R., Khanna, D., Whitfield, M. L., et al. (2022) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2022.09.652 · Cited by 36 · see citing works
Self-citationAnti-Aging Drugs and the Related Signal Pathways
Du, N., Ruigang, Y., Jiang, S., Niu, Z., Zhou, W., Liu, C., Gao, L., & Sun, Q. (2024) · Biomedicines · doi:10.3390/biomedicines12010127 · Cited by 37 · see citing works
Neutralization of oxidized phospholipids attenuates age‐associated bone loss in mice
Palmieri, M., Almeida, M., Nookaew, I., Gómez-Acevedo, H., Joseph, T. E., Que, X., Tsimikas, S., Sun, X., Manolagas, S. C., Witztum, J. L., et al. (2021) · Aging Cell · doi:10.1111/acel.13442 · Cited by 34 · see citing works
Targeting CD38 in Neoplasms and Non-Cancer Diseases
Szlasa, W., Czarny, J., Sauer, N. J., Rakoczy, K., Szymańska, N., Stecko, J., Kołodziej, M., Kaźmierczak, M., & Barg, E. (2022) · Cancers · doi:10.3390/cancers14174169 · Cited by 34 · see citing works
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Li, F., Wu, C., & Wang, G. (2023) · Neuroscience Bulletin · doi:10.1007/s12264-023-01072-3 · Cited by 33 · see citing works
CD38+ B cells affect immunotherapy for allergic rhinitis
Tian, G., Peng, K., Liu, M., Tian, D., Xie, H., Wang, L., Guo, Y., Zhou, S., Mo, L., & Yang, P. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2022.01.012 · Cited by 32 · see citing works
NAD + Precursors in Human Health and Disease: Current Status and Future Prospects
Yaku, K., & Nakagawa, T. (2023) · Antioxidants and Redox Signaling · doi:10.1089/ars.2023.0354 · Cited by 31 · see citing works
Roth‐Walter, F., Adcock, I. M., Benito‐Villalvilla, C., Bianchini, R., Bjermer, L. H., Caramori, G., Cari, L., Chung, K. F., Diamant, Z., Eguíluz‐Gracia, I., et al. (2023) · Allergy · doi:10.1111/all.15977 · Cited by 31 · see citing works
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Gao, L., Liu, Y., Du, X., Ma, S., Ge, M., Tang, H., Han, C., Zhao, X., Liu, Y., Shao, Y., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03968-2 · Cited by 31 · see citing works
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Alabarse, P. V. G., Chen, L.-Y., Oliveira, P., Qin, H., & Liu‐Bryan, R. (2022) · Arthritis & Rheumatology · doi:10.1002/art.42351 · Cited by 31 · see citing works
Ratia, K. M., Shen, Z., Gordon-Blake, J. M., Lee, H., Laham, M. S., Krider, I. S., Christie, N., Ackerman-Berrier, M. S., Penton, C., Knowles, N. G., et al. (2023) · Biochemistry · doi:10.1021/acs.biochem.2c00655 · Cited by 30 · see citing works
TNB-738, a biparatopic antibody, boosts intracellular NAD+ by inhibiting CD38 ecto-enzyme activity
Ugamraj, H. S., Dang, K. H., Ouisse, L., Buelow, B., Chini, E. N., Castello, G., Allison, J., Clarke, S., Davison, L. M., Buelow, R., et al. (2022) · mAbs · doi:10.1080/19420862.2022.2095949 · Cited by 31 · see citing works
Self-citationWalzik, D., Jonas, W., Joisten, N., Belen, S., Wüst, R. C. I., Guillemin, G. J., & Zimmer, P. (2023) · Acta Physiologica · doi:10.1111/apha.13921 · Cited by 32 · see citing works
CD38 regulates ovarian function and fecundity via NAD+ metabolism
Perrone, R., Kumaar, P. V. A., Haky, L., Hahn, C., Riley, R. R., Balough, J. L., Zaza, G., Soygur, B., Hung, K., Prado, L., et al. (2023) · iScience · doi:10.1016/j.isci.2023.107949 · Cited by 29 · see citing works
Imai, S. (2025) · npj Aging · doi:10.1038/s41514-025-00192-6 · Cited by 29 · see citing works
Chronic HIV Infection and Aging: Application of a Geroscience-Guided Approach
Masters, M. C., LANDAY, A. L., Robbins, P. D., Tchkonia, T., Kirkland, J. L., Kuchel, G. A., Niedernhofer, L. J., & Palella, F. J. (2022) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0000000000002858 · Cited by 29 · see citing works
Self-citationSARS-CoV-2 infection dysregulates NAD metabolism
Izadpanah, A., Mudd, J. C., Garcia, J. G. N., Srivastav, S., Abdel‐Mohsen, M., Palmer, C. S., Goldman, A. R., Kolls, J. K., Qin, X., & Rappaport, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1158455 · Cited by 29 · see citing works
The ageing immune system as a driver of systemic ageing
Jang, I. H., Niedernhofer, L. J., Robbins, P. D., & Camell, C. D. (2026) · Nature reviews. Immunology · doi:10.1038/s41577-026-01269-3 · Cited by 33 · see citing works
Evolving roles of CD38 metabolism in solid tumour microenvironment
Gao, L., Du, X., Li, J., & Qin, F. X.-F. (2022) · British Journal of Cancer · doi:10.1038/s41416-022-02052-6 · Cited by 28 · see citing works
Pgc-1α controls epidermal stem cell fate and skin repair by sustaining NAD+ homeostasis during aging
Wong, W., Crane, E. D., Zhang, H., Li, J., Day, T. A., Green, A. E., Menzies, K. J., & Crane, J. D. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101575 · Cited by 27 · see citing works
Cros, C. D., Margier, M., Cannelle, H., Charmetant, J., Hulo, N., Laganier, L., Grozio, A., & Canault, M. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.895028 · Cited by 27 · see citing works
Advances in the Synthesis and Physiological Metabolic Regulation of Nicotinamide Mononucleotide
Zheng, C., Li, Y., Wu, X., Gao, L., & Chen, X. (2024) · Nutrients · doi:10.3390/nu16142354 · Cited by 26 · see citing works
Understanding and targeting senescence in kidney disease
Chanvillard, L., Mason, T., & Ferenbach, D. A. (2025) · Clinical Kidney Journal · doi:10.1093/ckj/sfaf190 · Cited by 26 · see citing works
NAD+ Metabolism and Interventions in Premature Renal Aging and Chronic Kidney Disease
Chanvillard, L., Tammaro, A., & Sorrentino, V. (2022) · Cells · doi:10.3390/cells12010021 · Cited by 25 · see citing works
Targeting NAD+ Metabolism to Modulate Autoimmunity and Inflammation
Wu, J., Han, K., & Sack, M. N. (2024) · The Journal of Immunology · doi:10.4049/jimmunol.2300693 · Cited by 25 · see citing works
- Authors
- Chini, C. C. S., Peclat, T. R., Warner, G. M., Kashyap, S., Espindola-Netto, J. M., de Oliveira, G. C., Gomez, L. S., Hogan, K. A., Tarragó, M. G., Puranik, A. S., Agorrody, G., Thompson, K. L., Dang, K., Clarke, S., Childs, B. G., Kanamori, K. S., Witte, M. A., Vidal, P., Kirkland, A. L., De Cecco, M., Chellappa, K., McReynolds, M. R., Jankowski, C., Tchkonia, T., Kirkland, J. L., Sedivy, J. M., van Deursen, J. M., Baker, D. J., van Schooten, W., Rabinowitz, J. D., Baur, J. A., & Chini, E. N.
- Affiliations
- Mayo Clinic (US)
- University of Pennsylvania (US)
- Princeton University (US)
- Brown University (US)
- Corresponding author
- Chini, Eduardo N.
- ORCID
- Chini, Claudia C. S.
- Peclat, Thais R.
- Kashyap, Sonu
- Espindola-Netto, Jair Machado
- Gomez, Lilian S.
- Hogan, Kelly A.
- Puranik, Amrutesh S.
- Agorrody, Guillermo
- Dang, Kevin
- Clarke, Starlynn
- Childs, Bennett G.
- Kanamori, Karina S.
- Witte, Micaela A.
- Vidal, Paola
- Chellappa, Karthikeyani
- McReynolds, Melanie R.
- Jankowski, Connor
- Tchkonia, Tamara
- Kirkland, James L.
- Sedivy, John M.
- Baker, Darren J.
- Rabinowitz, Joshua D.
- Baur, Joseph A.
- Chini, Eduardo N.
- Venue
- Nature Metabolism
- Published
- 2020-11-16
- Volume
- 2
- Issue
- 11
- Pages
- 1284-1304
- ISSN
- 2522-5812 (ISSN-L)
- PMC
- PMC8752031
- OpenAlex
- W3104775068
- Cited by
- 349
- References
- 90
- Citations by year
- 2026: 57 · 2025: 69 · 2024: 74 · 2023: 50 · 2022: 63 · 2021: 31 · 2020: 5
- FWCI
- 19.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG058812, R37AG016694, R01AG057493, R01AG013925, R01AG016694, R01AG026094, R37AG013925, P01AG051449)
- National Cancer Institute (R01CA233790)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK098656)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21AR074523)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- CD38, aging, NAD+ homeostasis, nicotinamide mononucleotide, senescence-associated secretory phenotype, senescent cells, immune cells, white adipose tissue, liver, inflammation, metabolic dysfunction
- MeSH terms
- Aging, Animals, Humans, Inflammation, Liver, Membrane Glycoproteins, Mice, Inbred C57BL, Mice, Transgenic, NAD, Nicotinamide Mononucleotide, Phenotype, Bone Marrow Transplantation, Cellular Senescence, Mice, Knockout, Mice, ADP-ribosyl Cyclase 1, Adipose Tissue, White, Adipocytes, White, HEK293 Cells
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