During human aging, decrease of NAD levels is associated with potentially reversible dysfunction in the liver, kidney, skeletal and cardiac muscle, endothelial cells, and neurons. At the same time, the number of senescent cells, associated with damage or stress that secretes proinflammatory factors (SASP or senescence-associated secretory phenotype), increases with age in many key tissues, including the kidneys, lungs, blood vessels, and brain. Senescent cells are believed to contribute to numerous age-associated pathologies and their elimination by senolytic regimens appears to help in numerous preclinical aging-associated disease models, including those for atherosclerosis, idiopathic pulmonary fibrosis, diabetes, and osteoarthritis. A recent report links these processes, such that decreased NAD levels associated with aging may attenuate the SASP potentially reducing its pathological effect. Conversely, increasing NAD levels by supplementation or genetic manipulation, which may benefit tissue homeostasis, also may worsen SASP and encourage tumorigenesis at least in mouse models of cancer. Taken together, these findings suggest a fundamental trade-off in treating aging-related diseases with drugs or supplements that increase NAD. Even more interesting is a report that senescent cells can induce CD38 on macrophages and endothelial cells. In turn, increased CD38 expression is believed to be the key modulator of lowered NAD levels with aging in mammals. So, accumulation of senescent cells may itself be a root cause of decreased NAD, which in turn could promote dysfunction. On the contrary, the lower NAD levels may attenuate SASP, decreasing the pathological influence of senescence. The elimination of most senescent cells by senolysis before initiating NAD therapies may be beneficial and increase safety, and in the best-case scenario reduce the need for NAD supplementation.
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http://dx.doi.org/10.1089/rej.2019.2218 | DOI Listing |
Exp Anim
January 2025
Division of Medical Sciences, Institute of Medicine, University of Tsukuba.
Unbalanced redox homeostasis leads to the production of reactive oxygen species and exacerbates inflammatory bowel disease. To investigate the role of the transcription factor Nrf2, a major antioxidative stress sensor, in intestinal epithelial cells (IECs), we generated IEC-specific Nrf2 gene knock-in mice (Nrf2-vRes), which express Nrf2 only in IECs, using the cre/loxp system. Colitis was induced in wild-type (WT) mice, whole-body Nrf2-knockout (Nrf2-KO) mice, and Nrf2-vRes mice by administering dextran sulfate sodium (DSS) for 1 week (acute model) or intermittently for 5 weeks (chronic model).
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January 2025
Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
Objective: Metabolic reprogramming plays a critical role in modulating the innate and adaptive immune response, but its role in cutaneous autoimmune diseases, such as cutaneous lupus erythematosus (CLE), is less well studied. An improved understanding of the metabolic pathways dysregulated in CLE may lead to novel treatment options, biomarkers and insights into disease pathogenesis. The objective was to compare metabolomic profiles in the skin and sera of CLE and control patients using liquid chromatography-mass spectrometry (LC-MS).
View Article and Find Full Text PDFMolecules
January 2025
Orlen Unicre a.s., Revolucňí 1521/84, 400 01 Ústí nad Labem, Czech Republic.
The increasing global population and urbanization have led to significant challenges in waste management, particularly concerning vacuum blackwater (VBW), which is the wastewater generated from vacuum toilets. Traditional treatment methods, such as landfilling and composting, often fall short in terms of efficiency and sustainability. Anaerobic digestion (AD) has emerged as a promising alternative, offering benefits such as biogas production and digestate generation.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland.
Hepatocellular carcinoma (HCC) cells critically depend on PARP1 and CHK1 activation for survival. Combining the PARP inhibitor (PARPi) olaparib with a CHK1 inhibitor (MK-8776, CHK1i) produced a synergistic effect, reducing cell viability and inducing marked oxidative stress and DNA damage, particularly in the HepG2 cells. This dual treatment significantly increased apoptosis markers, including γH2AX and caspase-3/7 activity.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
College of Pharmacy, California Northstate University, Elk Grove, CA 95757, USA.
Over-accumulation of reactive oxygen species (ROS) causes hepatocyte dysfunction and apoptosis that might lead to the progression of liver damage. Sirtuin-3 (SIRT3), the main NAD+-dependent deacetylase located in mitochondria, has a critical role in regulation of mitochondrial function and ROS production as well as in the mitochondrial antioxidant mechanism. This study explores the roles of astragaloside IV (AST-IV) and formononetin (FMR) in connection with SIRT3 for potential antioxidative effects.
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