Effects of Maillard reaction and its product AGEs on aging and age-related diseases

Maillard reaction(MR)is a non-enzymatic browning reaction commonly seen in food processing,which occurs between reducing sugars and compounds with amino groups.Despite certain advantages based on Maillard reaction products(MRPs)found in some food for health and storage application have appeared,however,the MR occurring in human physiological environment can produce advanced glycation end products(AGEs)by non-enzymatic modification of macromolecules such as proteins,lipids and nucleic acid,which could change the structure and functional activity of the molecules themselves.In this review,we take AGEs as our main object,on the one hand,discuss physiologic aging,that is,age-dependent covalent cross-linking and modification of proteins such as collagen that occur in eyes and skin containing connective tissue.On the other hand,pathological aging associated with autoimmune and inflammatory diseases,neurodegenerative diseases,diabetes and diabetic nephropathy,cardiovascular diseases and bone degenerative diseases have been mainly proposed.Based on the series of adverse effects of accelerated aging and disease pathologies caused by MRPs,the possible harm caused by some MR can be slowed down or inhibited by artificial drug intervention,dietary pattern and lifestyle control.It also stimulates people's curiosity to continue to explore the potential link between the MR and human aging and health,which should be paid more attention to for the development of life sciences.

GPP(composition of Ganoderma lucidum polysaccharides and Polyporus umbellatus polysaccharides) protects against DSS-induced murine colitis by enhancing immune function and regulating intestinal flora

Previous study have demonstrated that a compound composed of water-soluable Ganoderma lucidum polysaccharides(GLP)and Polyporus umbellatus polysaccharides(PUP)in a ratio of 3:1 named GPP enhances innate immune function in mice through enhancing the function of macrophage cells and activity of natural killer(NK)cells.Here in our research,we further investigated the effect of GPP on the diversity and composition of intestinal flora,and explored its effect on colitis model mice.The immunoregulatory verification experiments of GPP were conducted in both normal and DSS-induced mice model.Our research showed that GPP increased the diversity of intestinal microorganisms in mice with the extension of administration time.Daily GPP intake attenuated DSS-induced colon injury,protected the splenic lymphocyte proliferation ability,enhanced the serum hemolysin synthesis,and increased peripheral phagocytes and NK cell activity in model mice.Comparisons of the predominant gene pathways of the bacterial microbiota showed that DNA repair and recombination,base mismatch repair pathways was stronger in GPP-treatment group than in control group,indicating the possible molecular mechanisms of immune function regulation.Our study showed that GPP regulated immune function in both health and colitis model,and had a positive effect on maintaining intestinal flora homeostasis.

Ellagic acid ameliorates cisplatin-induced acute kidney injury by regulating inflammation and SIRT6/TNF-α signaling

De spite cisplatin has been widely used in the treatment of various cancers,the noteworthy nephrotoxicity greatly constrained its clinical value.For this reason,finding novel targeted therapies to attenuate the nephrotoxicity of cisplatin should be pretty significant.Our previous study found that histone deacetylase sirtuin 6(SIRT6)could be an ideal target for the treatment of cisplatin-induced acute kidney injury.In this study,we explored the protective effects of ellagic acid,a natural polyphenol compound that activates SIRT6,on cisplatin-induced nephrotoxicity.Pre-treatment of ellagic acid attenuated cytotoxicity of cisplatin in primary renal cells and TCMK-1 cells.Moreover,ellagic acid ameliorated renal dysfunction,apoptosis and fibrosis induced by cisplatin in mice.Furthermore,ellagic acid reduced nephrotoxicity-associated inflammatory factor interleukin(IL)-1βand IL-6 expression both in vitro and in vivo.Mechanistically,ellagic acid reversed cisplatin-reduced SIRT6 expression and diminished cisplatin-induced tumor necrosis factor(TNF)-αexpression.And SIRT6 knockdown abrogated the protective effects of ellagic acid on cisplatin-induced cell apoptosis,indicating the renal-protective effects of ellagic acid are mainly dependent on ellagic acid-mediated SIRT6 activation.Our results provide preclinical rationale for using ellagic acid as a feasible and promising agent to ameliorate cisplatin-induced acute kidney injury,and support ellagic acid as a potential adjunctive therapy for future cancer treatment.

High-starchy carbohydrate diet aggravates NAFLD by increasing fatty acids influx mediated by NOX2

Nonalcoholic fatty liver disease(NAFLD)is a high-incidence lipid disorder that affects more than a quarter of the population worldwide,and dietary intervention is the recognized treatment.Starch is the main component of staple foods that are consumed daily,and the effects,metabolic pathway,and molecular mechanism of starch in the context of NAFLD remain unclear.Our study showed that a high-starch carbohydrate diet(HCD)led to the occurrence and exacerbation of NAFLD in mice.Transcriptomics and metabonomic analyses showed that the increased fatty acid influx mediated by NADPH oxidase 2(NOX2)exacerbated NAFLD.Knocking down NOX2 specifically alleviated HCD-induced NAFLD in vivo and in vitro.Moreover,the large amounts of ROS produced by NOX2 further exacerbated insulin resistance and increased lipolysis in perirenal white adipose tissue(periWAT),thereby providing fatty acids for hepatic lipid synthesis.In addition,the interaction between AMPKα1 and p47phox was the pathway that mediated the high expression of NOX2 induced by a HCD.Our study systematically demonstrated the effect of a HCD on NAFLD.Elevated fatty acid influx is a unique molecular regulatory pathway that mediates HCD-induced NAFLD exacerbation,which is different from the effect of simple sugars.Additionally,NOX2 was suggested to be a specific and effective drug target for NAFLD.

Decoding aging:examining the non-evolutionary event from an evolutionary perspective

In an era marked by increased longevity,a deeper understanding of the older population is vital.By introducing an overlooked evolutionary perspective on aging,this article challenges traditional biogerontology,which primarily focuses on biological and clinical aspects.It articulately differentiates between chronological and physiological aging,suggesting that aging is an evolutionary byproduct rather than a direct evolutionary event.