skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


Title: Dietary natural products as epigenetic modifiers in aging-associated inflammation and disease
Covering: up to 2020 Chronic, low-grade inflammation is linked to aging and has been termed “inflammaging”. Inflammaging is considered a key contributor to the development of metabolic dysfunction and a broad spectrum of diseases or disorders including declines in brain and heart function. Genome-wide association studies (GWAS) coupled with epigenome-wide association studies (EWAS) have shown the importance of diet in the development of chronic and age-related diseases. Moreover, dietary interventions e.g. caloric restriction can attenuate inflammation to delay and/or prevent these diseases. Common themes in these studies entail the use of phytochemicals (plant-derived compounds) or the production of short chain fatty acids (SCFAs) as epigenetic modifiers of DNA and histone proteins. Epigenetic modifications are dynamically regulated and as such, serve as potential therapeutic targets for the treatment or prevention of age-related disease. In this review, we will focus on the role for natural products that include phytochemicals and short chain fatty acids (SCFAs) as regulators of these epigenetic adaptations. Specifically, we discuss regulators of methylation, acetylation and acylation, in the protection from chronic inflammation driven metabolic dysfunction and deterioration of neurocognitive and cardiac function.  more » « less
Award ID(s):
1826801
PAR ID:
10168181
Author(s) / Creator(s):
; ;
Date Published:
Journal Name:
Natural Product Reports
Volume:
37
Issue:
5
ISSN:
0265-0568
Page Range / eLocation ID:
653 to 676
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; (, Antioxidants)
    Santos, AL (Ed.)
    Peroxisomes are key regulators of cellular and metabolic homeostasis. These organelles play important roles in redox metabolism, the oxidation of very-long-chain fatty acids (VLCFAs), and the biosynthesis of ether phospholipids. Given the essential role of peroxisomes in cellular homeostasis, peroxisomal dysfunction has been linked to various pathological conditions, tissue functional decline, and aging. In the past few decades, a variety of cellular signaling and metabolic changes have been reported to be associated with defective peroxisomes, suggesting that many cellular processes and functions depend on peroxisomes. Peroxisomes communicate with other subcellular organelles, such as the nucleus, mitochondria, endoplasmic reticulum (ER), and lysosomes. These inter-organelle communications are highly linked to the key mechanisms by which cells surveil defective peroxisomes and mount adaptive responses to protect them from damages. In this review, we highlight the major cellular changes that accompany peroxisomal dysfunction and peroxisomal inter-organelle communication through membrane contact sites, metabolic signaling, and retrograde signaling. We also discuss the age-related decline of peroxisomal protein import and its role in animal aging and age-related diseases. Unlike other organelle stress response pathways, such as the unfolded protein response (UPR) in the ER and mitochondria, the cellular signaling pathways that mediate stress responses to malfunctioning peroxisomes have not been systematically studied and investigated. Here, we coin these signaling pathways as “peroxisomal stress response pathways”. Understanding peroxisomal stress response pathways and how peroxisomes communicate with other organelles are important and emerging areas of peroxisome research. 
    more » « less
  2. ; ; ; ; ; (, Nutrients)
    The gut microbiome plays an important role in human health and influences the development of chronic diseases ranging from metabolic disease to gastrointestinal disorders and colorectal cancer. Of increasing prevalence in Western societies, these conditions carry a high burden of care. Dietary patterns and environmental factors have a profound effect on shaping gut microbiota in real time. Diverse populations of intestinal bacteria mediate their beneficial effects through the fermentation of dietary fiber to produce short-chain fatty acids, endogenous signals with important roles in lipid homeostasis and reducing inflammation. Recent progress shows that an individual’s starting microbial profile is a key determinant in predicting their response to intervention with live probiotics. The gut microbiota is complex and challenging to characterize. Enterotypes have been proposed using metrics such as alpha species diversity, the ratio of Firmicutes to Bacteroidetes phyla, and the relative abundance of beneficial genera (e.g., Bifidobacterium, Akkermansia) versus facultative anaerobes (E. coli), pro-inflammatory Ruminococcus, or nonbacterial microbes. Microbiota composition and relative populations of bacterial species are linked to physiologic health along different axes. We review the role of diet quality, carbohydrate intake, fermentable FODMAPs, and prebiotic fiber in maintaining healthy gut flora. The implications are discussed for various conditions including obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, depression, and cardiovascular disease. 
    more » « less
  3. ; ; ; ; ; ; ; ; ; ; et al (, Scientific Reports)
    Abstract Neopterin, a product of activated white blood cells, is a marker of nonspecific inflammation that can capture variation in immune investment or disease-related immune activity and can be collected noninvasively in urine. Mounting studies in wildlife point to lifetime patterns in neopterin related to immune development, aging, and certain diseases, but rarely are studies able to assess whether neopterin can capture multiple concurrent dimensions of health and disease in a single system. We assessed the relationship between urinary neopterin stored on filter paper and multiple metrics of health and disease in wild geladas (Theropithecus gelada), primates endemic to the Ethiopian highlands. We tested whether neopterin captures age-related variation in inflammation arising from developing immunity in infancy and chronic inflammation in old age, inflammation related to intramuscular tapeworm infection, helminth-induced anti-inflammatory immunomodulation, and perturbations in the gastrointestinal microbiome. We found that neopterin had a U-shaped relationship with age, no association with larval tapeworm infection, a negative relationship with metrics related to gastrointestinal helminth infection, and a negative relationship with microbial diversity. Together with growing research on neopterin and specific diseases, our results demonstrate that urinary neopterin can be a powerful tool for assessing multiple dimensions of health and disease in wildlife. 
    more » « less
  4. ; ; ; ; ; ; ; ; ; ; et al (, Proceedings of the National Academy of Sciences)
    Intestinal barrier dysfunction, which leads to translocation of bacteria or toxic bacterial products from the gut into bloodstream and results in systemic inflammation, is a key pathogenic factor in many human diseases. However, the molecular mechanisms leading to intestinal barrier defects are not well understood, and there are currently no available therapeutic approaches to target intestinal barrier function. Here we show that soluble epoxide hydrolase (sEH) is an endogenous regulator of obesity-induced intestinal barrier dysfunction. We find that sEH is overexpressed in the colons of obese mice. In addition, pharmacologic inhibition or genetic ablation of sEH abolishes obesity-induced gut leakage, translocation of endotoxin lipopolysaccharide or bacteria, and bacterial invasion-induced adipose inflammation. Furthermore, systematic treatment with sEH-produced lipid metabolites, dihydroxyeicosatrienoic acids, induces bacterial translocation and colonic inflammation in mice. The actions of sEH are mediated by gut bacteria-dependent mechanisms, since inhibition or genetic ablation of sEH fails to attenuate obesity-induced gut leakage and adipose inflammation in mice lacking gut bacteria. Overall, these results support that sEH is a potential therapeutic target for obesity-induced intestinal barrier dysfunction, and that sEH inhibitors, which have been evaluated in human clinical trials targeting other human disorders, could be promising agents for prevention and/or treatment. 
    more » « less
  5. ; (, Functional Food Science)
    The gut microbiome incorporates the ecological niche specific to the totality of the microorganisms in the human gut. Unique to every individual, the blueprint of the microbiome sets up at birth and functions as a human organ and plays a significant role in digestion, detoxification, fighting pathogens, modulating the immune system, and improving health. The gut microbiota and associated health implications are influenced by factors such as birth and age, diseases, use of antibiotics and food components (e.g., complex carbohydrates and dietary fibers, plant proteins, unsaturated fatty acids, and functional compounds of natural origin such as flavones, flavonoids, polyphenols, and antioxidants). Toward this end, diet and the gut microbiome interact and govern each other’s fate. Herein, gut dysbiosis, the alteration of natural state and composition of the gut microbiome, and the gut microflora diversity modulated by food constituents and associated health effects have been discussed. The gut microbiota composition and related metabolites are influenced by the diet which in turn modulates human health. The outcome is deemed to aid in developing personalized diet recommendations (based on the unique gut microbiome) toward improving human health. Keywords: gut microbiome, gut microbiota, gut dysbiosis, short-chain fatty acids, metabolites, health modulation 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email