Myotis bat STING attenuates aging-related inflammation in female mice

Bats,notable as the only flying mammals,serve as natural reservoir hosts for various highly pathogenic viruses in humans(e.g.,SARS-CoV and Ebola virus).Furthermore,bats exhibit an unparalleled longevity among mammals relative to their size,particularly the Myotis bats,which can live up to 40 years.However,the mechanisms underlying these distinctive traits remain incompletely understood.In our prior research,we demonstrated that bats exhibit dampened STING-interferon activation,potentially conferring upon them the capacity to mitigate virus-or aging-induced inflammation.To substantiate this hypothesis,we established the first in vivo bat-mouse model for aging studies by integrating Myotis davidii bat STING(MdSTING)into the mouse genome.We monitored the genotypes of these mice and performed a longitudinal comparative transcriptomic analysis on MdSTING and wild-type mice over a 3-year aging process.Blood transcriptomic analysis indicated a reduction in aging-related inflammation in female MdSTING mice,as evidenced by significantly lower levels of pro-inflammatory cytokines and chemokines,immunopathology,and neutrophil recruitment in aged female MdSTING mice compared to aged wild-type mice in vivo.These results indicated that MdSTING knock-in attenuates the aging-related inflammatory response and may also improve the healthspan in mice in a sex-dependent manner.Although the underlying mechanism awaits further study,this research has critical implications for bat longevity research,potentially contributing to our comprehension of healthy aging in humans.

SIRT3 regulates mitochondrial biogenesis in aging-related diseases

Sirtuin 3(SIRT3),the main family member of mitochondrial deacetylase,targets the majority of substrates controlling mitochondrial biogenesis via lysine deacetylation and modulates important cellular functions such as energy metabolism,reactive oxygen species production and clearance,oxidative stress,and aging.Deletion of SIRT3 has a deleterious effect on mitochondrial biogenesis,thus leading to the defect in mitochondrial function and insufficient ATP production.Imbalance of mitochondrial dynamics leads to excessive mitochondrial biogenesis,dampening mitochondrial function.Mitochondrial dysfunction plays an important role in several diseases related to aging,such as cardiovascular disease,cancer and neurodegenerative diseases.Peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC1α)launches mitochondrial biogenesis through activating nuclear respiratory factors.These factors act on genes,transcribing and translating mitochondrial DNA to generate new mitochondria.PGC1αbuilds a bridge between SIRT3 and mitochondrial biogenesis.This review described the involvement of SIRT3 and mitochondrial dynamics,particularly mitochondrial biogenesis in agingrelated diseases,and further illustrated the role of the signaling events between SIRT3 and mitochondrial biogenesis in the pathological process of aging-related diseases.

Construction and evaluation of a novel prognostic risk model of aging-related genes in bladder cancer

Background:Bladder cancer(BLCA)is the most common malignancy of the urinary system.Muscle-invasive bladder cancer(MIBC),which constitutes approximately 25%of all BLCA cases,is characterized by frequent recurrence and early onset of metastasis.Bladder cancer most commonly occurs in elderly patients and is significantly associated with aging.However,the prognostic value of age-related genes in BLCA,especially in MIBC,remains unclear.Materials and methods:Training and testing sets were obtained from The Cancer Genome Atlas BLCA project.Differentially expressed genes between BLCA and normal samples intersected with human aging-related genes.Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were used to identify prognostic aging-related signatures,followed by the construction of a risk score model and nomogram.Kaplan-Meier and receiver operating characteristic analyses were conducted to assess the predictive power.An independent BLCA cohort of 165 samples was included for external validation.The CIBERSORT algorithm was used to explore the characteristics of the immune microenvironment.Results:Seven genes(IGF1,NGF,GCLM,PYCR1,EFEMP1,APOC3,and IFNB1)were identified by Cox and least absolute shrinkage and selection operator analyses.After combining the gene signature with the clinical parameters of patients with BLCA,a risk-prognosis model and nomogram were constructed and validated with the testing set.Bladder cancer cases with high 7-gene signature scores(high-risk group)and low scores(low-risk group)showed distinct prognoses.Furthermore,7 types of immune cells were significantly altered between the low-and high-risk groups.Conclusions:Collectively,our data provide a 7-gene signature that serves as a potential biomarker for BLCA,especially MIBC.Moreover,this 7-gene signature highlights the role of the tumor immune microenvironment in prognosis and thus might be related to the response to anti-programmed cell death protein 1-based immunotherapy.

Sirtuins Function as the Modulators in Aging-related Diseases in Common or Respectively

INTRODUCTIONAccording to the demographics, the world population over 60 years will double from 605 million to 2 billion people between 2000 and 2050. Aging is a complex process in which the organism and its ability to respond to external stresses become progressive decline.

Nattokinase as a functional food ingredient:therapeutic applications and mechanisms in age-related diseases

Consumption of natto,a traditional eastern Asian food made of fermented soybeans by Bacillus subtilis,has long been linked to healthy aging and longer human lifespan.As the key thrombolytic ingredient of natto,the serine protease nattokinase(NK)has been developed into a widely-used dietary supplement.NK has shown excellent anti-thrombus,thrombolytic,and anti-inflammation activities that potentially delay aging and provide therapeutic effects on aging-related diseases.In this review,we critically overview the experimental and clinical evidence in the past 20 years that support the beneficial function of NK in the prevention and treatment of aging-related diseases,including cardiovascular diseases,Alzheimer’s disease,other abnormalities and cancer.We focus on the underlying molecular mechanisms and recent advances in application methods that are aimed at further development of NK for healthier aging of modern society.The challenges and unsolved issues in this area are also discussed.

Linking gut microbiota to aging process:a new target for anti-aging

The human gut microbiota is a huge ecosystem that provides lots of functions for host development,immune system,and metabolism.Gut microbiota is linked to lots of diseases,including human metabolic diseases such as obesity,type 2 diabetes(T2D),irritable bowel syndrome,and cardiovascular disease(CVD).Few studies,however,have noted the relationship between aging and microbiota,the connection between aging and microbiota remain largely to be researched.In this review,recent research findings are summarized on the role of gut microbiota in aging processes with emphasis on therapeutic potential of microbiome-targeted interventions in anti-aging medicine.

Mitochondrial sirtuins,metabolism,and aging

Maintaining metabolic homeostasis is essential for cellular and organismal health throughout life.Multiple signaling pathways that regulate metabolism also play critical roles in aging,such as PI3K/AKT,mTOR,AMPK,and sirtuins(SIRTs).Among them,sirtuins are known as a protein family with versatile functions,such as metabolic control,epigenetic modification and lifespan extension.Therefore,by understanding how sirtuins regulate metabolic processes,we can start to understand how they slow down or accelerate biological aging from the perspectives of metabolic regulation.Here,we review the biology of SIRT3,SIRT4,and SIRT5,known as the mitochondrial sirtuins due to their localization in the mitochondrial matrix.First,we will discuss canonical pathways that regulate metabolism more broadly and how these are integrated with aging regulation.Then,we will summarize the current knowledge about functional differences between SIRT3,SIRT4,and SIRT5 in metabolic control and integration in signaling networks.Finally,we will discuss how mitochondrial sirtuins regulate processes associated with aging and aging-related diseases.