Activation of innate immunity system during aging: NF-kB signaling is the molecular culprit of inflamm-aging

Salminen, Antero; Huuskonen, Juhani; Ojala, Johanna; Kauppinen, Anu; Kaarniranta, Kai; Suuronen, Tiina

doi:10.1016/j.arr.2007.09.002

Cited by 478 publications

(367 citation statements)

References 281 publications

Supporting

Mentioning

341

Contrasting

Unclassified

Order By: Relevance

“…As predicted, a significant enrichment of upregulated genes implicated in inflammatory response and Cytokine/Chemokine activity were observed. Additionally, up-regulated genes involved in the NF-κB cascade were also enriched in the aged stroma, consistent with recent reports suggesting a role of the NF-κB transcription factor signaling in mammalian aging [14][15][16] . For the down-regulated genes, collagen binding and pro-collagen genes were significantly enriched, in accordance to our observation that procollagen genes are down-regulated with aging.…”

Section: Bodysupporting

confidence: 77%

The Aged Microenvironment Influences Prostate Carcinogenesis

Bianchi-Frias¹

2008

View full text Add to dashboard Cite

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information SPONSOR/MONITOR'S REPORT NUMBER(S)12. DISTRIBUTION / AVAILABILITY STATEMENT Approved for public release; distribution unlimited SUPPLEMENTARY NOTES14. ABSTRACT The greatest factor for the development of prostate adenocarcinoma is advanced age. Emerging evidence suggests that molecular alterations in the aged prostate microenvironment mediated by stromal aging and senescence are key factors regulating carcinogenesis and neoplastic progression. We used normal mouse prostate epithelial and adjacent stromal cells microdissected in situ from young and old animals, to identify factors altered by the aged stroma that may place the prostate gland at risk for developing prostate cancer. Expression profiling demonstrated clear differences in gene expression between old and young prostate stroma, with 63 genes exhibiting significant transcript abundance levels given a moderate estimate of false positive differences of 10%. Genes associated with inflammation, oxidative stress, and structural proteins were among the genes most substantially altered with aging. Factors identified in this study, such as ApoD and Ccl8, were selectively expressed and up-regulated only in the aged prostate stroma and not in the prostatic epithelium or inflammatory cells. The aged prostate microenvironment was characterized by a pro-inflammatory gene expression profile and the presence of high numbers of inflammatory cells. Additionally, structural alterations were observed in the aged prostate. Fluorescence and ultrastructural microscopic analysis revealed a collagen matrix network significantly disrupted in the aged prostate. It is plausible that both the alteration in the collagenous stroma and the infiltration of inflammatory cells are likely to be acting in concert with one another to produce fundamental changes in both the prostate epithelial and stromal cells that can lead to prostate tumorigenesis and/or progression. We propose that these changes contribute in a coordinated way to induce and/or sustain prostate tumorigenesis-on one hand by altering the extracellular matrix and, on the other, signaling through the NK-kB pathway for immune infiltration. Taken together, these observations may aid in a better understanding of the causative role of aging in human prostate cancer development and progression SUBJECT TERMS

show abstract

Section: Bodysupporting

confidence: 77%

The Aged Microenvironment Influences Prostate Carcinogenesis

Bianchi-Frias¹

2008

View full text Add to dashboard Cite

show abstract

“…Aging is proposed to activate inflammatory pathways [12][13][14][15][16] . Also, inflammation is a core causal pathway of RA 12 as well as a contributor to some of its comorbid diseases and mortality, such as cardiovascular 17 .…”

Section: Biological Relations Of Aging and Inflammationmentioning

confidence: 99%

“…Within such a holistic framework of RA, a relevant question might be whether or not this disease is importantly induced by underlying determinants of accelerated biological aging, more than is currently recognized. Specifically, might genetic and behavioral/environmental-related mechanisms that actively induce aging 13,15,16 [12][13][14][15][16] may help to dissect the complex web of interacting susceptibility factors for RA 18,19 .…”

Section: Biological Relations Of Aging and Inflammationmentioning

confidence: 99%

Hypothalamic-Pituitary-Gonadal Axis Hormones and Male Rheumatoid Arthritis: Novel Perspectives

Masi¹,

Chatterton²,

Aldag³

2009

J Rheumatol

View full text Add to dashboard Cite

“…The aging intestine is subject to a number of physiological changes that impact on food digestion and absorption (25,26) and immune function (27). Accompanied by a loss in the proportions of naïve CD4 + T cells, the inflamm-aging process is characterized by persistent activation of innate immunity mediated by the NF-ĸB transcription factor (28). Given the potential for elements of the microbiota to impact on these dynamic processes, there is considerable interest in determining the composition of the gut microbiota of elderly subjects and characterizing its variation as a potential determinant of health (3).…”

mentioning

confidence: 99%

Composition, variability, and temporal stability of the intestinal microbiota of the elderly

Claesson

Cusack

O'Sullivan

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

1,438

1,149

View full text Add to dashboard Cite

Alterations in the human intestinal microbiota are linked to conditions including inflammatory bowel disease, irritable bowel syndrome, and obesity. The microbiota also undergoes substantial changes at the extremes of life, in infants and older people, the ramifications of which are still being explored. We applied pyrosequencing of over 40,000 16S rRNA gene V4 region amplicons per subject to characterize the fecal microbiota in 161 subjects aged 65 y and older and 9 younger control subjects. The microbiota of each individual subject constituted a unique profile that was separable from all others. In 68% of the individuals, the microbiota was dominated by phylum Bacteroides, with an average proportion of 57% across all 161 baseline samples. Phylum Firmicutes had an average proportion of 40%. The proportions of some phyla and genera associated with disease or health also varied dramatically, including Proteobacteria, Actinobacteria, and Faecalibacteria. The core microbiota of elderly subjects was distinct from that previously established for younger adults, with a greater proportion of Bacteroides spp. and distinct abundance patterns of Clostridium groups. Analyses of 26 fecal microbiota datasets from 3-month follow-up samples indicated that in 85% of the subjects, the microbiota composition was more like the corresponding time-0 sample than any other dataset. We conclude that the fecal microbiota of the elderly shows temporal stability over limited time in the majority of subjects but is characterized by unusual phylum proportions and extreme variability.

show abstract

Activation of innate immunity system during aging: NF-kB signaling is the molecular culprit of inflamm-aging

Cited by 478 publications

References 281 publications

The Aged Microenvironment Influences Prostate Carcinogenesis

The Aged Microenvironment Influences Prostate Carcinogenesis

Hypothalamic-Pituitary-Gonadal Axis Hormones and Male Rheumatoid Arthritis: Novel Perspectives

Composition, variability, and temporal stability of the intestinal microbiota of the elderly

Contact Info

Product

Resources

About