Long-term dasatinib plus quercetin effects on aging outcomes and inflammation in nonhuman primates: implications for senolytic clinical trial design - Peeref (2024)

Article Biochemistry & Molecular Biology

Changing the dietary composition improves inflammation but not adipocyte thermogenesis in diet-induced obese mice

Sabrina Folie, Bernhard Radlinger, Georg Goebel, Karin Salzmann, Gabriele Staudacher, Claudia Ress, Herbert Tilg, Susanne Kaser

Summary: The study suggests that switching from a metabolically harmful Western diet to a balanced standard diet can improve adipose tissue inflammation, while long-term consumption of a Western diet negatively impacts the thermogenic capacity of brown adipose tissue and inhibits beiging of white adipose tissue.

Review Nutrition & Dietetics

Adipose Tissue Aging and Metabolic Disorder, and the Impact of Nutritional Interventions

Xiujuan Wang, Meihong Xu, Yong Li

Summary: Adipose tissue, as the largest endocrine organ, plays a crucial role in regulating energy balance and immune function. Nutritional interventions have been proven effective in managing adipose tissue aging's adverse effects.

Article Cell Biology

Effects of different maternal diets on adipose tissue inflammation and liver tissue oxidative stress in dams and their female offspring

Joana Fisch, Ana Carolina de Moura, Vanessa Feistauer, Luiza Steffens Reinhardt, Patricia Molz, Ana Moira Moras, Dinara Jaqueline Moura, Priscila Oliveira de Souza, Elizandra Braganhol, Silvana Almeida, Renata Padilha Guedes, Alethea Gatto Barschak, Marcia Giovenardi

Summary: This study investigated the effects of different maternal diets during pregnancy and lactation on adipose tissue inflammation and liver tissue oxidative stress in both mothers and their female offspring. The results showed that a hypercaloric diet led to non-alcoholic steatohepatitis (NASH) and increased inflammation in mothers. A restricted diet caused increased inflammation in the offspring. In conclusion, maternal diet during pregnancy and lactation affects the liver and adipose tissues in both mothers and their offspring.

Article Nutrition & Dietetics

Navy Bean Supplementation in Established High-Fat Diet-Induced Obesity Attenuates the Severity of the Obese Inflammatory Phenotype

Jennifer M. Monk, Wenqing Wu, Dion Lepp, K. Peter Pauls, Lindsay E. Robinson, Krista A. Power

Summary: Cooked common beans can improve intestinal health and inflammation in obese mice, with greater benefits compared to weight loss through diet control alone. This suggests that incorporating beans into the diet can have a positive impact on obesity-related health issues beyond just weight loss.

Article Cell Biology

microRNAs-mediated regulation of insulin signaling in white adipose tissue during aging: Role of caloric restriction

Patricia Corrales, Marina Martin-Taboada, Yurena Vivas-Garcia, Lucia Torres, Laura Ramirez-Jimenez, Yamila Lopez, Daniel Horrillo, Rocio Vila-Bedmar, Eloisa Barber-Cano, Adriana Izquierdo-Lahuerta, Maria Pena-Chilet, Carmen Martinez, Joaquin Dopazo, Manuel Ros, Gema Medina-Gomez

Summary: Caloric restriction is a non-pharmacological intervention that improves metabolic defects associated with aging. MiRNA expression levels can serve as predictive tools for aging-related alterations. Specific miRNAs contribute to impaired insulin-stimulated glucose metabolism in subcutaneous white adipose tissue, and their expression is modified by caloric restriction, suggesting their potential as biomarkers for age-related metabolic alterations.

Review Nutrition & Dietetics

Vitamin D and Visceral Obesity in Humans: What Should Clinicians Know?

Prapimp*rn Chattranukulchai Shantavasinkul, Hataikarn Nimitphong

Summary: The effects of vitamin D on adipose tissue biology and modulation in human obesity are still inconclusive. While the anti-inflammatory effects of vitamin D are evident and consistent, its effects on adipocyte differentiation, adipogenesis, energy metabolism, and adipokine levels remain uncertain.

Review Biochemistry & Molecular Biology

Contribution of PGC-1 alpha to Obesity- and Caloric Restriction-Related Physiological Changes in White Adipose Tissue

Masaki Kobayashi, Yusuke Deguchi, Yuka Nozaki, Yoshikazu Higami

Summary: PGC-1 alpha plays a crucial role in regulating mitochondrial function and adipocyte-specific functions in white adipose tissue, with its function being affected by metabolic changes such as obesity and caloric restriction.

Article Immunology

The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging

Seungjin Ryu, Sviatoslav Sidorov, Eric Ravussin, Maxim Artyomov, Akiko Iwasaki, Andrew Wang, Vishwa Deep Dixit

Summary: Caloric restriction reduces the risk of chronic diseases caused by aging. The matricellular protein SPARC converts anti-inflammatory macrophages into pro-inflammatory cells and induces interferon-stimulated gene expression. Furthermore, SPARC inhibits mitochondrial respiration and is involved in immunometabolic regulation.

Review Biochemistry & Molecular Biology

Physiological Approaches Targeting Cellular and Mitochondrial Pathways Underlying Adipose Organ Senescence

Pieter de Lange, Assunta Lombardi, Elena Silvestri, Federica Cioffi, Antonia Giacco, Stefania Iervolino, Giuseppe Petito, Rosalba Senese, Antonia Lanni, Maria Moreno

Summary: The adipose organ plays a crucial role in metabolic functions and its aging process leads to metabolic disorders, impacting healthy aging. Cellular senescence in adipose tissue affects adipogenesis, inflammation, and adipocytokine production, leading to systemic inflammation, insulin resistance, and declined physiological features. Aging fat depots involve various cell types, highlighting their contribution to metabolic disorders. Targeting mitochondria may hold potential in managing adipose tissue senescence and treating age-related metabolic disorders.

Article Medicine, Research & Experimental

Inhibition of adipose tissue angiogenesis prevents rebound weight gain after caloric restriction in mice fed a high-fat diet

Hye-Jin Lee, Bo-Yeong Jin, Mi-Rae Park, Nam Hoon Kim, Kwan Sik Seo, Yong Taek Jeong, Tsutomu Wada, Jun-Seok Lee, Sang-Hyun Choi, Dong-Hoon Kim

Summary: This study investigated the role of modulation of the WAT vasculature in regulating RWG after CR and found that it can attenuate RWG by suppressing hyperphagia and increasing BAT thermogenesis and WAT browning.

Article Biology

The effects of caloric restriction on adipose tissue and metabolic health are sex- and age-dependent

Karla J. Suchacki, Benjamin J. Thomas, Yoshiko M. Ikushima, Kuan-Chan Chen, Claire Fyfe, Adriana A. S. Tavares, Richard J. Sulston, Andrea Lovdel, Holly J. Woodward, Xuan Han, Domenico Mattiucci, Eleanor J. Brain, Carlos J. Alcaide-Corral, Hiroshi Kobayashi, Gillian A. Gray, Phillip D. Whitfield, Roland H. Stimson, Nicholas M. Morton, Alexandra M. Johnstone, William P. Cawthorn

Summary: Studies have shown that caloric restriction (CR) can reduce the risk of age-related diseases in various species, including humans. However, there are sex and age-dependent differences in the metabolic effects of CR. Young female mice showed less improvement in fat loss, glucose tolerance, and insulin sensitivity compared to young males, which may be due to differences in lipolysis, energy expenditure, and fatty acid oxidation. Furthermore, the sex differences in glucose homeostasis were associated with altered hepatic ceramide content and substrate metabolism. In aged mice and overweight/obese humans, the sex differences in CR's effects were reduced or absent. These findings highlight the importance of adipose tissue, the liver, and estrogen as key determinants of CR's metabolic benefits.

Article Agriculture, Dairy & Animal Science

The effects of zinc amino acid complex on biomarkers of gut integrity, inflammation, and metabolism in heat-stressed ruminants

J. Opgenorth, M. Abuajamieh, E. A. Horst, S. K. Kvidera, J. S. Johnson, E. J. Mayorga, M. Sanz-Fernandez, M. A. Al-Qaisi, J. M. DeFrain, D. H. Kleinschmit, P. J. Gorden, L. H. Baumgard

Summary: The study found that heat stress had a significant impact on the steers, but supplementing with zinc amino acid complex improved some thermal indices, intestinal architecture characteristics, and reduced symptoms of leaky gut.

Article Biochemistry & Molecular Biology

Dietary interventions in mice affect oxidative stress and gene expression of the Prlr and Esr1 in the adipose tissue and hypothalamus of dams and their offspring

Mariana Fraga Gauthier, Andressa Alves de Andrade, Joana Fisch, Vanessa Feistauer, Ana Moira Moras, Luiza Steffens Reinhardt, Ana Carolina de Moura, Dinara Jaqueline Moura, Silvana de Almeida, Renata Padilha Guedes, Marcia Giovenardi

Summary: Maternal diet has an impact on the progeny's health and adult life. This study reveals that maternal diet affects oxidative stress levels and gene expression related to energy metabolism in the adipose tissue and hypothalamus of the offspring.

Article Food Science & Technology

Curcumin Reduces Adipose Tissue Inflammation and Alters Gut Microbiota in Diet-Induced Obese Male Mice

Tariful Islam, Iurii Koboziev, Kembra Albracht-Schulte, Brandon Mistretta, Shane Scoggin, Mohammad Yosofvand, Hanna Moussa, Masoud Zabet-Moghaddam, Latha Ramalingam, Preethi H. Gunaratne, Naima Moustaid-Moussa

Summary: The research suggests that curcumin supplementation can significantly reduce fat accumulation and decrease total macrophage infiltration in WAT, as well as lower mRNA levels of M1 and M2 macrophage markers. Furthermore, curcumin supplementation can also reduce the expression of other key pro-inflammatory genes in WAT, and exert protective metabolic effects through alterations in gut microbiota composition.

Article Food Science & Technology

The Dose-Dependent Effect of Curcumin Supplementation on Inflammatory Response and Gut Microbiota Profile in High-Fat Fed C57BL/6 Mice

Caroline Bertoncini-Silva, Priscila Giacomo Fassini, Daniela Carlos, Natalia Aparecida de Paula, Leandra Naira Zambelli Ramalho, Marina Rodrigues Giuliani, italo Sousa Pereira, Jhefferson Barbosa Guimaraes, Vivian Marques Miguel Suen

Summary: After 12 weeks of high-fat diet feeding and oral supplementation with curcumin in mice, it was found that curcumin reduces inflammatory markers and increases anti-inflammatory markers in the liver and white adipose tissue. In the gut, curcumin promotes the growth of beneficial bacteria and reduces harmful bacteria.

Article Neurosciences

Dysregulation of Elongation Factor 1A Expression is Correlated with Synaptic Plasticity Impairments in Alzheimer's Disease

Brenna C. Beckelman, Stephen Day, Xueyan Zhou, Maggie Donohue, Gunnar K. Gouras, Eric Klann, C. Dirk Keene, Tao Ma

Article Neurosciences

Glucagon-like peptide-1 cleavage product GLP-1 (9-36) amide enhances hippocampal long-term synaptic plasticity in correlation with suppression of Kv4.2 expression and eEF2 phosphorylation

Stephen M. Day, Wenzhong Yang, Sarah Ewin, Xueyan Zhou, Tao Ma

Editorial Material Neurosciences

Therapeutic Potential of Glucagon-Like Peptide-1 Cleavage Product for Alzheimer's Disease

Stephen M. Day, Tao Ma

Article Neurosciences

Type-2-Diabetes Alters CSF but Not Plasma Metabolomic and AD Risk Profiles in Vervet Monkeys

Kylie Kavanagh, Stephen M. Day, Morgan C. Pait, William R. Mortiz, Christopher B. Newgard, Olga Ilkayeva, Donald A. Mcclain, Shannon L. Macauley

Article Neurosciences

A nonhuman primate model of human non-suicidal self-injury: serotonin-transporter genotype-mediated typologies

Elizabeth K. Wood, Ryno Kruger, Jaclyn P. Day, Stephen M. Day, Jacob N. Hunter, Leslie Neville, Stephen G. Lindell, Christina S. Barr, Melanie L. Schwandt, David Goldman, Stephen J. Suomi, James C. Harris, J. Dee Higley

Summary: Research on rhesus macaques suggests that early parental neglect and variation in the serotonin transporter genotype could play a role in the etiology of NSSI. NSSI subjects with different 5-HTT genotypes exhibited distinct behaviors, highlighting the complexity of NSSI typologies.

Article Neurosciences

Ethanol exposure alters Alzheimer's-related pathology, behavior, and metabolism in APP/PS1 mice

Stephen M. Day, Stephen C. Gironda, Caitlin W. Clarke, J. Andy Snipes, Noelle I. Nicol, Hana Kamran, Warner Vaughan, Jeffrey L. Weiner, Shannon L. Macauley

Summary: This study used a moderate drinking paradigm to investigate the effects of chronic ethanol exposure on Alzheimer's disease-related pathology, behavior, and metabolism. Ethanol-exposed mice showed increased brain atrophy, amyloid plaques, and shifts in plaque size distribution. They also exhibited deficits in self-care, increased locomotor activity, altered feeding behavior, and changes in glucose homeostasis. These findings suggest that ethanol may increase A beta deposition by disrupting metabolism and the brain's E/I balance, ultimately leading to AD-related phenotypes.

Article Medicine, Research & Experimental

KATP channels are necessary for glucose- dependent increases in amyloid-β and Alzheimer's disease-related pathology

John Grizzanti, William R. Moritz, Morgan C. Pait, Molly Stanley, Sarah D. Kaye, Caitlin M. Carroll, Nicholas J. Constantino, Lily J. Deitelzweig, James A. Snipes, Derek Kellar, Emily E. Caesar, Ryan J. Pettit-Mee, Stephen M. Day, Jonathon P. Sens, Noelle I. Nicol, Jasmeen Dhillon, Maria S. Remedi, Drew D. Kiraly, Celeste M. Karch, Colin G. Nichols, David M. Holtzman, Shannon L. Macauley

Summary: Elevated blood glucose levels can increase brain excitability and A beta release, linking type 2 diabetes and Alzheimer's disease. The KATP channels, which couple energy availability with cellular excitability, play a role in AD pathogenesis. Manipulation of Kir6.2-KATP channels may hold therapeutic promise in reducing A beta pathology in patients with diabetes or prediabetes.

Review Neurosciences

Social inequalities in health in nonhuman primates

Carol A. Shively, Stephen M. Day