Infection susceptibility,poor vaccination efficacy,age-related disease onset,and neoplasms are linked to innate and adaptive immune dysfunction that accompanies aging(known as immunosenescence).During aging,organisms ...Infection susceptibility,poor vaccination efficacy,age-related disease onset,and neoplasms are linked to innate and adaptive immune dysfunction that accompanies aging(known as immunosenescence).During aging,organisms tend to develop a characteristic inflammatory state that expresses high levels of pro-inflammatory markers,termed inflammaging.This chronic inflammation is a typical phenomenon linked to immunosenescence and it is considered the major risk factor for age-related diseases.Thymic involution,naïve/memory cell ratio imbalance,dysregulated metabolism,and epigenetic alterations are striking features of immunosenescence.Disturbed T-cell pools and chronic antigen stimulation mediate premature senescence of immune cells,and senescent immune cells develop a proinflammatory senescence-associated secretory phenotype that exacerbates inflammaging.Although the underlying molecular mechanisms remain to be addressed,it is well documented that senescent T cells and inflammaging might be major driving forces in immunosenescence.Potential counteractive measures will be discussed,including intervention of cellular senescence and metabolic-epigenetic axes to mitigate immunosenescence.In recent years,immunosenescence has attracted increasing attention for its role in tumor development.As a result of the limited participation of elderly patients,the impact of immunosenescence on cancer immunotherapy is unclear.Despite some surprising results from clinical trials and drugs,it is necessary to investigate the role of immunosenescence in cancer and other age-related diseases.展开更多
Bovine foamy virus encodes a transcriptional transactivitor, Tas or Borf-1, which governs the level of viral transcripts initiated by both the promoter in the long terminal repeat (LTR) and the internal promoter (IP) ...Bovine foamy virus encodes a transcriptional transactivitor, Tas or Borf-1, which governs the level of viral transcripts initiated by both the promoter in the long terminal repeat (LTR) and the internal promoter (IP) located in the env gene through their cis-acting targets. We have identified and characterized a 72 bp TBS (Borf-1) responsive element located in BFV3026, internal promoter (TREIP) by deletion mutant and transient expression assay. This cis-acting target element in the internal promoter has the properties of a transcriptional enhancer which functions independently of its orientation, position and also in heterologous promoters (BFV LTR and bovine immunodeficiency virus, BIV LTR). Alignments reveal that there are positional similarity and sequence homology among BFV TREIP, SFV-1 TREIP proximal element and SFV-3 TREIPH, which suggests that this kind of cis-acting elements possesses some common functional character.展开更多
文摘Infection susceptibility,poor vaccination efficacy,age-related disease onset,and neoplasms are linked to innate and adaptive immune dysfunction that accompanies aging(known as immunosenescence).During aging,organisms tend to develop a characteristic inflammatory state that expresses high levels of pro-inflammatory markers,termed inflammaging.This chronic inflammation is a typical phenomenon linked to immunosenescence and it is considered the major risk factor for age-related diseases.Thymic involution,naïve/memory cell ratio imbalance,dysregulated metabolism,and epigenetic alterations are striking features of immunosenescence.Disturbed T-cell pools and chronic antigen stimulation mediate premature senescence of immune cells,and senescent immune cells develop a proinflammatory senescence-associated secretory phenotype that exacerbates inflammaging.Although the underlying molecular mechanisms remain to be addressed,it is well documented that senescent T cells and inflammaging might be major driving forces in immunosenescence.Potential counteractive measures will be discussed,including intervention of cellular senescence and metabolic-epigenetic axes to mitigate immunosenescence.In recent years,immunosenescence has attracted increasing attention for its role in tumor development.As a result of the limited participation of elderly patients,the impact of immunosenescence on cancer immunotherapy is unclear.Despite some surprising results from clinical trials and drugs,it is necessary to investigate the role of immunosenescence in cancer and other age-related diseases.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 39970033 ) Doctoral Fund in High School (Grant No. 98005516).
文摘Bovine foamy virus encodes a transcriptional transactivitor, Tas or Borf-1, which governs the level of viral transcripts initiated by both the promoter in the long terminal repeat (LTR) and the internal promoter (IP) located in the env gene through their cis-acting targets. We have identified and characterized a 72 bp TBS (Borf-1) responsive element located in BFV3026, internal promoter (TREIP) by deletion mutant and transient expression assay. This cis-acting target element in the internal promoter has the properties of a transcriptional enhancer which functions independently of its orientation, position and also in heterologous promoters (BFV LTR and bovine immunodeficiency virus, BIV LTR). Alignments reveal that there are positional similarity and sequence homology among BFV TREIP, SFV-1 TREIP proximal element and SFV-3 TREIPH, which suggests that this kind of cis-acting elements possesses some common functional character.