Unveiling the role of NAD glycohydrolase CD38 in aging and age-related diseases: insights from bibliometric analysis and comprehensive review

Abstract

Background: CD38, a glycoprotein with a single transmembrane structure, is extensively found in erythrocytes, immune cells, and endothelial cells. Primarily located on cell membranes, it plays a critical role in metabolizing nicotinamide adenine dinucleotide (NAD), thereby maintaining NAD homeostasis in vivo. As a vital coenzyme, NAD is involved in numerous biological processes, including energy metabolism, apoptosis, and DNA repair. CD38, as a major NAD-depleting enzyme, is pivotal in regulating intracellular NAD levels and various physiological processes. Given its significance, understanding the function of CD38 and its implications in aging and age-related diseases is crucial for elucidating disease pathogenesis and developing therapeutic strategies.

Methods: This study conducted a bibliometric analysis to explore recent research trends and advancements in the field of CD38. Research articles were retrieved from the Web of Science database, followed by a bibliometric assessment using CiteSpace and VOSviewer to visualize key publication trends, contributions by countries and institutions, and keyword distributions. Based on the bibliometric analysis, key insights were synthesized to elucidate the role of CD38 in aging and age-related diseases, its underlying mechanisms, and its applications in clinical evaluation, detection methods, interventions, and therapeutic targets.

Results: The bibliometric analysis revealed an exponential increase in the number of published articles over time, with the United States and China emerging as the leading research hubs. The predominant keywords included 'CD38' and 'blood-related disorders'. Furthermore, key findings highlighted the critical role of CD38 in aging and age-related diseases, emphasizing its mechanisms in NAD metabolism and its potential as a therapeutic target. Moreover, current applications of CD38 in clinical evaluation and detection methods were discussed, showcasing its growing importance in biomedical research.

Conclusion: This study underscores the growing interest in CD38 research, particularly its role in aging and age-related diseases. The findings highlight the significance of CD38 in maintaining NAD homeostasis and its potential as a therapeutic target. The exponential growth in publications and the dominance of the United States and China in this field reflect the global importance of CD38 research. Future studies should further explore the mechanistic insights and clinical applications of CD38 to advance therapeutic strategies for age-related diseases.

Keywords: CD38; aging; bibliometric analysis; metabolic diseases; tumors.

Figure 1

Flow chart of the study.

Figure 2

Number of publications per year and the cumulative number.

Figure 3

Research keywords on CD38 in aging and age-related diseases. (A) Keyword clusters color-coded by research themes; (B) Temporal evolution of research topics; (C) Refined keyword clusters identified by CiteSpace; (D) Top 25 keywords with strongest citation bursts.

Figure 4

CiteSpace visualization map of timeline viewer related to CD38 in aging and age-related diseases.

Figure 5

The systemic outcomes of increased CD38 activity across various organs. This figure illustrates the various diseases associated with increased circulating CD38 activity among different organs. A wide range of organs, including the brain, lungs, heart and vascular system, mammary glands, gastrointestinal tract, pancreas, liver, prostate, immune system, and hematologic, are closely related to the increase in CD38 activity in the blood (A). In addition to disease states, enhanced CD38 activity is also associated with aging, with its activity gradually increasing with age (B).

Figure 6

Mechanisms of CD38 activity changes and aging. This figure illustrates the biological mechanisms by which changes in CD38 activity impact aging processes. Secretion of SASP by senescent cells or activation of innate immune cells via PAMP promotes macrophage M1 polarization thereby significantly enhancing CD38 activity in M1 macrophages and increasing hydrolysis of NAD to generate NAM, while the NAD precursors NMN and NR also generate NAM (A); while inhibition of using the CD38-specific inhibitor 78c significantly reduces this process, reducing NAD hydrolysis and thereby enhancing age-related metabolic dysfunction and prolonging the lifespan and health span(B). SASP, Senescence-associated secretory phenotype; PAMP, Pathogen-associated molecular patterns; TLR, Toll-like receptors; SIRT, Sirtuin; PARP, poly ADP-ribose polymerase; NAD, Nicotinamide adenine dinucleotide; NAM, Nicotinamide; NMN, Nicotinamide mononucleotide; NR, Nicotinamide riboside; NMNAT, Nicotinamide mononucleotide adenylyl transferase; NAMPT, Nicotinamide phosphoribosyl transferase.