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Antiviral innate immune response receptor RIG-I (DEAD box protein 58) (Probable ATP-dependent RNA helicase DDX58) (EC (RIG-I-like receptor 1) (RLR-1) (Retinoic acid-inducible gene 1 protein) (RIG-1) (Retinoic acid-inducible gene I protein) (RIG-I)


Transcriptome analysis reveals immune-related gene expression changes with age in giant panda ([i]Ailuropoda melanoleuca[/i]) blood.

The giant panda ([i]Ailuropoda melanoleuca[/i]), an endangered species endemic to western China, has long been threatened with extinction that is exacerbated by highly contagious and fatal diseases. Aging is the most well-defined risk factor for diseases and is associated with a decline in immune function leading to increased susceptibility to infection and reduced response to vaccination. Therefore, this study aimed to determine which genes and pathways show differential expression with age in blood tissues. We obtained 210 differentially expressed genes by RNA-seq, including 146 up-regulated and 64 down-regulated genes in old pandas (18-21yrs) compared to young pandas (2-6yrs). We identified ISG15, STAT1, IRF7 and DDX58 as the hub genes in the protein-protein interaction network. All of these genes were up-regulated with age and played important roles in response to pathogen invasion. Functional enrichment analysis indicated that up-regulated genes were mainly involved in innate immune response, while the down-regulated genes were mainly related to B cell activation. These may suggest that the innate immunity is relatively well preserved to compensate for the decline in the adaptive immune function. In conclusion, our findings will provide a foundation for future studies on the molecular mechanisms underlying immune changes associated with ageing.

MeSH Terms

  • Aging
  • Animals
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Transcriptome
  • Ursidae


  • ageing
  • gene expression
  • giant panda
  • immune system
  • transcriptome

Age-associated mRNA expression changes in bovine endometrial cells in vitro.

Endometrial cells secrete various cytokines and the dysfunction of endometrial cells may directly lead to infertility. Interferon tau (IFNT) secreted by trophoblast cells, a well-known pregnancy recognition signal in ruminants, acts on the uterus to prepare for pregnancy. Aging causes cellular and organ dysfunction, and advanced maternal age is associated with reduced fertility. However, few studies have investigated age-dependent changes in the uterus. Using next generation sequencing and real-time PCR, we examined mRNA expression in bovine endometrial cells in vitro obtained from young (mean 45.2 months) and aged (mean 173.5 months) animals and the effects of IFNT depending on the age. We showed that inflammation-related (predicted molecules are IL1A, C1Qs, DDX58, NFKB, and CCL5) and interferon-signaling (predicted molecules are IRFs, IFITs, STATs, and IFNs) pathways were activated in endometrial cells obtained from aged compared to young cows. Also, the activation of "DNA damage checkpoint regulation" and the inhibition of "mitotic mechanisms" in endometrial cells obtained from aged cows were evident. Moreover, we showed lower cell viability levels in endometrial cells obtained from aged compared to young cows. Although treatment with IFNT upregulated various types of interferon stimulated genes both in endometrial cells obtained from young and aged cows, the rate of increase by IFNT stimulus was obviously lower in endometrial cells obtained from aged compared to young cows. Endometrial cells obtained from aged cows exhibited higher levels of inflammatory- and IFN-signaling, and dysfunction of cell division compared with young cows. In addition, a high basal level of IFN-related genes in endometrial cells of aged cows is suggested a concept of "inflammaging".

MeSH Terms

  • Age Factors
  • Animals
  • Cattle
  • Cell Division
  • Cells, Cultured
  • Endometrium
  • Female
  • Gene Expression Profiling
  • Interferon Type I
  • Maternal Age
  • Pregnancy Proteins
  • RNA, Messenger
  • Signal Transduction


  • Aging
  • Cow
  • Inflammation
  • Interferon tau
  • Uterus

Progression of pathology in PINK1-deficient mouse brain from splicing via ubiquitination, ER stress, and mitophagy changes to neuroinflammation.

PINK1 deficiency causes the autosomal recessive PARK6 variant of Parkinson's disease. PINK1 activates ubiquitin by phosphorylation and cooperates with the downstream ubiquitin ligase PARKIN, to exert quality control and control autophagic degradation of mitochondria and of misfolded proteins in all cell types. Global transcriptome profiling of mouse brain and neuron cultures were assessed in protein-protein interaction diagrams and by pathway enrichment algorithms. Validation by quantitative reverse transcriptase polymerase chain reaction and immunoblots was performed, including human neuroblastoma cells and patient primary skin fibroblasts. In a first approach, we documented Pink1-deleted mice across the lifespan regarding brain mRNAs. The expression changes were always subtle, consistently affecting "intracellular membrane-bounded organelles". Significant anomalies involved about 250 factors at age 6 weeks, 1300 at 6 months, and more than 3500 at age 18 months in the cerebellar tissue, including Srsf10, Ube3a, Mapk8, Creb3, and Nfkbia. Initially, mildly significant pathway enrichment for the spliceosome was apparent. Later, highly significant networks of ubiquitin-mediated proteolysis and endoplasmic reticulum protein processing occurred. Finally, an enrichment of neuroinflammation factors appeared, together with profiles of bacterial invasion and MAPK signaling changes-while mitophagy had minor significance. Immunohistochemistry showed pronounced cellular response of Iba1-positive microglia and GFAP-positive astrocytes; brain lipidomics observed increases of ceramides as neuroinflammatory signs at old age. In a second approach, we assessed PINK1 deficiency in the presence of a stressor. Marked dysregulations of microbial defense factors Ifit3 and Rsad2 were consistently observed upon five analyses: (1) Pink1 primary neurons in the first weeks after brain dissociation, (2) aged Pink1 midbrain with transgenic A53T-alpha-synuclein overexpression, (3) human neuroblastoma cells with PINK1-knockdown and murine Pink1 embryonal fibroblasts undergoing acute starvation, (4) triggering mitophagy in these cells with trifluoromethoxy carbonylcyanide phenylhydrazone (FCCP), and (5) subjecting them to pathogenic RNA-analogue poly(I:C). The stress regulation of MAVS, RSAD2, DDX58, IFIT3, IFIT1, and LRRK2 was PINK1 dependent. Dysregulation of some innate immunity genes was also found in skin fibroblast cells from PARK6 patients. Thus, an individual biomarker with expression correlating to progression was not identified. Instead, more advanced disease stages involved additional pathways. Hence, our results identify PINK1 deficiency as an early modulator of innate immunity in neurons, which precedes late stages of neuroinflammation during alpha-synuclein spreading.

MeSH Terms

  • Age Factors
  • Aging
  • Animals
  • Calcium-Binding Proteins
  • Cells, Cultured
  • Cerebral Cortex
  • Disease Models, Animal
  • Disease Progression
  • Endoplasmic Reticulum Stress
  • Gene Expression Profiling
  • Humans
  • Lipid Metabolism
  • Mice
  • Mice, Transgenic
  • Microfilament Proteins
  • Mitophagy
  • Neuroblastoma
  • Neurons
  • Parkinson Disease
  • Protein Kinases
  • RNA Splicing
  • Ubiquitination
  • alpha-Synuclein


  • Antiviral response
  • Mitochondrial dysfunction
  • Neuroinflammation
  • Parkinson’s disease
  • Ubiquitin kinase PINK1