查看更多>>摘要：The concept of precision nutrition was first proposed almost a decade ago.Current research in precision nutrition primarily focuses on comprehending individualized variations in response to dietary intake,with little attention being given to other crucial aspects of precision nutrition.Moreover,there is a dearth of comprehensive review studies that portray the landscape and framework of precision nutrition.This review commences by tracing the historical trajectory of nutritional science,with the aim of dissecting the challenges encountered in nutrition science within the new era of disease profiles.This review also deconstructs the field of precision nutrition into four key components:the proposal of the theory for indi-vidualized nutritional requirement phenotypes;the establishment of precise methods for measuring dietary intake and evaluating nutritional status;the creation of multidimensional nutritional interven-tion strategies that address the aspects of what,how,and when to eat;and the construction of a pathway for the translation and integration of scientific research into healthcare practices,utilizing artificial intel-ligence and information platforms.Incorporating these four components,this review further discusses prospective avenues that warrant exploration to achieve the objective of enhancing health through pre-cision nutrition.
查看更多>>摘要：Skin aging is an increasingly prominent topic in the context of healthy aging.During the aging process,the skin's barrier function diminishes,its water content decreases,wrinkles begin to form,and changes occur in the gut microbiota composition.However,the relationship between gut microbiota and skin aging remains unclear.In this study,we explored skin rejuvenation in aged mice through fecal microbiota trans-plantation(FMT)using feces from young mice.The results demonstrated enhanced water retention,thick-ened stratum corneum,increased collagen content,and improved epithelial cell differentiation in aged mice following FMT.Notably,FMT particularly increased the abundance of Lactobacillus and Lactococcus in aged mice,which were nearly undetectable in untreated aged mice.Non-targeted and targeted meta-bolomics analyses indicated that FMT significantly elevated levels of tryptophan(Trp)and its microbiota metabolites(e.g.,indole-3-lactic acid(ILA))in the feces and serum of aged mice.Both Trp and ILA appeared to rejuvenate aged skin by activating the aryl hydrocarbon receptor(AhR)to promote epidermal cell dif-ferentiation.In conclusion,FMT from young mice rejuvenated aged skin via Trp-metabolizing bacteria(Lactobacillus and Lactococcus)and Trp-derived metabolites,suggesting that interventions targeting Trp metabolites may effectively improve skin aging.
查看更多>>摘要：Intestinal stem cells(ISCs)initiate intestinal epithelial regeneration and tumorigenesis,and they experi-ence rapid refilling upon various injuries for epithelial repair as well as tumor reoccurrence.It is crucial to reveal the mechanism underlying such plasticity for intestinal health.Recent studies have found that metabolic pathways control stem cell fate in homeostasis,but the role of metabolism in the regeneration of ISCs after damage has not been clarified.Here,we find that in a human colorectal cancer dataset,miR-29a and b(miR-29a/b)are metabolic regulators highly associated with intestinal tumorigenesis and worse prognostic value of radiotherapy.We also show that these two microRNAs are required for intesti-nal stemness maintenance in mice,and their expression is induced in regenerated ISCs after irradiation injury,resulting in skewed ISC fate from differentiation towards self-renewal.This upregulation of miR-29a/b expression in ISCs leads to suppression of fatty acid oxidation(FAO)and depression of oxidative phosphorylation,which in turn controls the balance between self-renewal and differentiation of ISCs.Deletion of miR-29a/b prevents these effects and thus impairs ISC-mediated epithelial recovery.Finally,we filter the potential targets of miR-29a/b and identify Hnf4g,a transcription factor,that drives this metabolic reprogramming through regulating FAO-related enzymes.Our work discovers an impor-tant metabolic mechanism of ISC-mediated regeneration and potentially pave the way for more targeted and effective therapeutic strategies for intestinal repair as well as tumor treatment.
查看更多>>摘要：Susceptibility to pathogens in the elderly is heightened with age,largely because of immunosenescence.As an immune regulatory organ,bone marrow creates immune cells that move to other organs and tis-sues through the blood.Despite the significance of this process of this organ,there is limited research on changes in immune cell generation in the bone marrow and their effects on immunosenescence.In this study,the compositions of immune cells in bone marrow from young(three months)and old(24+months)mice were compared by means of mass cytometry,with further validation obtained through the reanalysis of single-cell RNA sequencing data and cell sorting via flow cytometry.The effects of differential immune cells on immunosenescence in old mice were evaluated using the Clostridium difficile(C.difficile)infection model.Our results showed that aged mice presented with a reduction in bone tra-beculae structure,which was accompanied by a notable increase in polymorphonuclear(PMN)-myeloid-derived suppressor cell(MDSC)abundance.Through bulk-seq and reverse transcription quantitative polymerase chain reaction(RT-qPCR)analysis,we identified differential genes associated with the immune response-specifically,the Th17 cell differentiation pathway.Furthermore,the increase in exported PMN-MDSCs to the large intestine resulted in increased gut permeability and inflammatory damage to the colon following C.difficile infection.After clearing the PMN-MDSCs in old mice using the anti-Gr-1 antibody,the symptoms induced by C.difficile were significantly relieved,as evidenced by an inhibited IL-17 pathway in the colon and reduced gut permeability.In conclusion,aging increases the number of PMN-MDSCs in both the generated bone marrow and the outputted intestine,which con-tributes to susceptibility to C.difficile infection.This study provides a novel target for anti-aging therapy for immunosenescence,which is beneficial for improving immune function in elders.
查看更多>>摘要：Pulmonary fibrosis(PF)is a lethal lung disease that predominantly affects older adults;however,whether and how aging triggers fibrosis remains unclear.To pinpoint the predominant initiating factors of PF,we first analyzed single-cell RNA sequencing(scRNA-seq)data from the lung tissues of 45 normal donors and 51 PF patients and found that aging might serve as the primary catalyst for PF development.To further investigate the influence of aging on PF formation,we conducted a comprehensive and thorough study employing a natural aging mouse model.We found that dynamic alterations in the quantity and types of collagen fibers during aging-induced PF progression,especially in collagenous(Col)Ⅰ,emerged as the predominant driver of PF.We then investigated the regulation of Col Ⅰ synthesis during aging using primary alveolar type 2(AT2)cells and A549 cells line through conditioned media and Transwell cocul-ture,and found that secretions-particularly plasminogen activator inhibitor(PAI)-1-from aged AT2 cells promoted fibrosis and enhanced collagen type Ⅰ alpha 1(Col1al)production via the transforming growth factor(TGF)-β/small mother against decapentaplegic(Smad)2/3 pathway.Furthermore,scRNA-seq and a histological analysis of human lung tissue demonstrated a significant upregulation of SERPINE1(the gene encoding PAI-1)and PAI-1 expression in both aging lung tissue and AT2 cells,which was consistent with our findings from animal experiments,providing additional evidence for the pivotal role of PAI-1 during aging and the development of PF.Our research demonstrates that PAI-1,a crucial factor secreted by aging AT2 cells,exerts a pivotal role in promoting the synthesis of Col1a1 in fibroblasts,subsequently leading to Col Ⅰ deposition,and in driving the progression of PF by mediating the TGF-β/Smad2/3 pathway.Our find-ings offer critical evidence for the involvement of epithelial dysfunction in age-related PF and provides potential novel therapeutic targets for clinical intervention.
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