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The Sir2-p53-IGF link in mammalian life-span control

Description: PUBLIC HEALTH RELEVANCE: Paradoxically, robust growth and bigger size are not necessarily good predictors of a long and healthy life span. Despite the obvious significance of this observation, the mechanism that couples longevity and body size is poorly understood. We propose that it is the tumor suppressor p53 that links these two traits by controlling the switch from anaerobic to aerobic metabolism in stem cells.
Funding type: research
Funder scheme: R01
Start date: 2006-03-15
End date: 2018-05-31
Investigator: EDUARDO N CHINI
Institution: MAYO CLINIC ROCHESTER
Subfield: Aging
Funded outputs count: 44
Funder award ID: R01AG026094
OpenAlex ID: G8593207360
Inducible chronic NAD deficiency in mice reveals multi-systemic phenotypical, metabolic, and transcriptional changes
2026 · Andres Benitez-Rosendo, Morgan B. Feuz, et al. · Nature Communications
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Inhibition of CD38 enzyme activity on engrafted human immune cells enhances NAD+ metabolism and inhibits inflammation in an in-vivo model of xeno-GvHD
2025 · Ghenima Ahmil-Boiteau, Pranjali Dalvi, et al. · Frontiers in Immunology · 2
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A nitroalkene derivative of salicylate, SANA, induces creatine-dependent thermogenesis and promotes weight loss
2025 · Karina Cal, Alejandro Leyva, et al. · Nature Metabolism · 13
Chronic Cellular NAD Depletion Activates a Viral Infection‐Like Interferon Response Through Mitochondrial DNA Leakage
2025 · Claudia C. S. Chini, Laura Colman, et al. · Aging Cell · 14
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An NAD+-dependent metabolic checkpoint regulates hematopoietic stem cell activation and aging
2024 · Zehan Song, Sang Hee Park, et al. · Nature Aging · 51
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Ecto-CD38-NADase inhibition modulates cardiac metabolism and protects mice against doxorubicin-induced cardiotoxicity
2024 · Thais R Peclat, Guillermo Agorrody, et al. · Cardiovascular Research · 10
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NAD metabolism: Role in senescence regulation and aging
2023 · Claudia Christiano Silva Chini, Heidi Soares Cordeiro, et al. · Aging Cell · 150
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Endogenous metabolism in endothelial and immune cells generates most of the tissue vitamin B3 (nicotinamide)
2022 · Julianna D. Zeidler, Claudia C.S. Chini, et al. · iScience · 12
Senescent Cells Accumulate in Systemic Sclerosis Skin
2022 · Bo Shi, Pei-Suen Tsou, et al. · Journal of Investigative Dermatology · 36
Mitochondrial dysfunction in cell senescence and aging
2022 · Satomi Miwa, Sonu Kashyap, et al. · Journal of Clinical Investigation · 1,137
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CD38 inhibitor 78c increases mice lifespan and healthspan in a model of chronological aging
2022 · Thais R. Peclat, Katie L. Thompson, et al. · Aging Cell · 57
The CD38 glycohydrolase and the NAD sink: implications for pathological conditions
2022 · Julianna D. Zeidler, Kelly A. Hogan, et al. · American Journal of Physiology-Cell Physiology · 95
Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine-induced ventricular arrhythmias
2022 · Guillermo Agorrody, Thais R. Peclat, et al. · Journal of Molecular and Cellular Cardiology · 25
Cancer treatment-induced NAD+ depletion in premature senescence and late cardiovascular complications
2022 · Priyanka Banerjee, Elizabeth A. Olmsted-Davis, et al. · The Journal of Cardiovascular Aging · 10
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Implications of the NADase CD38 in COVID pathophysiology
2021 · Julianna D. Zeidler, Sonu Kashyap, et al. · Physiological Reviews · 27
Evolving concepts in NAD+ metabolism
2021 · Claudia C.S. Chini, Julianna D. Zeidler, et al. · Cell Metabolism · 301
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Targeting CD38-dependent NAD+ metabolism to mitigate multiple organ fibrosis
2020 · Bo Shi, Wenxia Wang, et al. · iScience · 74
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CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels
2020 · Claudia C. S. Chini, Thais R. Peclat, et al. · Nature Metabolism · 370
Implications of the PAPP-A-IGFBP-IGF-1 pathway in the pathogenesis and treatment of polycystic kidney disease
2020 · Sonu Kashyap, Julianna D. Zeidler, et al. · Cellular Signalling · 15
The Multi-faceted Ecto-enzyme CD38: Roles in Immunomodulation, Cancer, Aging, and Metabolic Diseases
2019 · Kelly A. Hogan, Claudia C. S. Chini, et al. · Frontiers in Immunology · 350
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The NADase CD38 is induced by factors secreted from senescent cells providing a potential link between senescence and age-related cellular NAD+ decline
2019 · Claudia Chini, Kelly A. Hogan, et al. · Biochemical and Biophysical Research Communications · 140
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Correction: Two Different Methods of Quantification of Oxidized Nicotinamide Adenine Dinucleotide (NAD+) and Reduced Nicotinamide Adenine Dinucleotide (NADH) Intracellular Levels: Enzymatic Coupled Cycling Assay and Ultra-performance Liquid Chromatography (UPLC)-Mass Spectrometry
2019 · Karina Kanamori, Guilherme de Oliveira, et al. · BIO-PROTOCOL · 1
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Correction Notice: Measuring CD38 Hydrolase and Cyclase Activities: 1,N6-Ethenonicotinamide Adenine Dinucleotide (ε-NAD) and Nicotinamide Guanine Dinucleotide (NGD) Fluorescence-based Methods
2019 · Guilherme de Oliveira, Karina Kanamori, et al. · BIO-PROTOCOL
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A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline
2018 · Mariana G. Tarragó, Claudia C.S. Chini, et al. · Cell Metabolism · 391
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The Pharmacology of CD38/NADase: An Emerging Target in Cancer and Diseases of Aging
2018 · Eduardo N. Chini, Claudia C.S. Chini, et al. · Trends in Pharmacological Sciences · 233
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