Unraveling brain aging through the lens of oral microbiota

The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

In Silico analysis and linking of metabolism-related genes with the immune landscape in head and neck squamous cell carcinoma

Metabolic reprogramming and immunologic suppression are two critical characteristics promoting the progression of head and neck squamous cell carcinoma(HNSCC).The integrative analysis of all the metabolismrelated genes(MRGs)in HNSCC is lacking and the interaction between the metabolism and the immune characteristics also requires more exploration to uncover the potential mechanisms.Therefore,this study was designed to establish a prognostic signature based on all the MRGs in HNSCC.Genes of HNSCC samples were available from the TCGA and GEO databases while the MRGs were retrieved from a previous study.Ultimately 4 prognostic MRGs were selected to construct a model possessing robust prognostic value and accuracy in TCGA cohorts.The favorable reproducibility of this model was confirmed in validation cohorts from GEO databases.The risk score calculated by this model was an independent prognostic factor that further classified these HNSCC patients into high-/low-risk groups.GSEA analyses and somatic mutations indicated the low-risk group could activate several anti-tumor pathways and possessed lower TP53 mutation.The results of ESTIMATE,single-sample GSEA,CIBERSORT,and some immune-related molecules analyses suggested the low-risk group exhibited lower metabolic activities and higher immune characteristics.The Spearman correlation test implied most metabolic pathways with tumor-promoting function were negatively correlated with the immune activity,indicating a plausible approach of combining the anti-metabolism and the immunotherapy drugs in the high-risk group to enhance therapeutic effects than applied separately.In conclusion,this prognostic signature linking MRGs with the immune landscape could promote the individualized treatment for HNSCC patients.

Single-nucleus transcriptomics uncovers a geroprotective role of YAP in primate gingival aging

Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis,a worldwide prevalent inflammatory disease.However,a systematic characterization and comprehensive understanding of the regulatory mechanism underlying gingival aging is still lacking.Here,we systematically dissected the phenotypic characteristics of gingiva during aging in primates and constructed the first single-nucleus transcriptomic landscape of gingival aging,by which a panel of cell type-specific signatures were elucidated.Epithelial cells were identified as the most affected cell types by aging in the gingiva.Further analyses pinpointed the crucial role of YAP in epithelial self-renew and homeostasis,which declined during aging in epithelial cells,especially in basal cells.The decline of YAP activity during aging was confrmed in the human gingival tissues,and downregulation of YAP in human primary gingival keratinocytes recapitulated the major phenotypic defects observed in the aged primate gingiva while overexpression of YAP showed rejuvenation effects.Our work provides an in-depth understanding of gingival aging and serves as a rich resource for developing novel strategies to combat aging-associated gingival diseases,with the ultimate goal of advancing periodontal health and promoting healthy aging.

Epigenetic regulation of aging:implications for interventions of aging and diseases

Aging is accompanied by the decline of organismal functions and a series of prominent hallmarks,including genetic and epigenetic alterations.These aging-associated epigenetic changes include DNA methylation,histone modification,chromatin remodeling,non-coding RNA(ncRNA)regulation,and RNA modification,all of which participate in the regulation of the aging process,and hence contribute to aging-related diseases.Therefore,understanding the epigenetic mechanisms in aging will provide new avenues to develop strategies to delay aging.Indeed,aging interventions based on manipulating epigenetic mechanisms have led to the alleviation of aging or the extension of the lifespan in animal models.Small molecule-based therapies and reprogramming strategies that enable epigenetic rejuvenation have been developed for ameliorating or reversing aging-related conditions.In addition,adopting health-promoting activities,such as caloric restriction,exercise,and calibrating circadian rhythm,has been demonstrated to delay aging.Furthermore,various clinical trials for aging intervention are ongoing,providing more evidence of the safety and efficacy of these therapies.Here,we review recent work on the epigenetic regulation of aging and outline the advances in intervention strategies for aging and age-associated diseases.A better understanding of the critical roles of epigenetics in the aging process will lead to more clinical advances in the prevention of human aging and therapy of aging-related diseases.