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Aging and vascular endothelial cell senescence: potential role of SIRT1 in development of inflammation and dysfunction
Author(s) -
Blimline Mark,
Seals Douglas,
Nelson Keri,
Rippe Catarina
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb81
Subject(s) - senescence , inflammation , endothelial dysfunction , sirtuin 1 , endothelium , population , in vivo , medicine , endothelial stem cell , endocrinology , monocyte , biology , immunology , in vitro , downregulation and upregulation , biochemistry , microbiology and biotechnology , environmental health , gene
Aging leads to vascular endothelial dysfunction, but the mechanisms involved are incompletely understood. We assessed the effects of aging on endothelial cell (EC) senescence in vivo and the possible role of the anti‐senescence and anti‐inflammatory deacetylase, SIRT1, in vitro . Compared with young adult (5 mo) mice, old (30 mo) mice had reduced endothelium‐dependent dilation and a higher % of aortic EC that stained for the senescence marker p16 INK4a (31 vs. 6). "Aged" cultures of human aortic EC (HAEC) (35±2 population doublings, PDL) had a higher % of cells stained for p16 INK4a (46 vs. 7) and (beta)‐galactosidase, a 2nd marker of senescence (57 vs. 6), than "young" cultures (20±1 PDL). SIRT1 expression was 55% lower in senescent HAEC (0.45±0.08 vs. 1.00 ± 0.10 AUs, P<0.002). Senescent HAEC demonstrated reduced expression of the anti‐inflammatory proteins interleukin‐10 (0.6±0.05 vs. 1.0±0.2 AUs, P<0.05) and interleukin‐1 receptor‐α (0.7±0.05 vs. 1.0±0.2 AUs, P<0.05), and increased expression of the inflammatory protein monocyte chemoattractant protein‐1 (1.6±0.1 vs. 1.0±0.1 AUs, P<0.005). In conclusion, the % of senescent arterial EC in vivo is greater in old age. A decrease in SIRT1 may play an important role in EC senescence and contribute to development of vascular endothelial inflammation and dysfunction. Swedish Research Council; NIH AG006537 , AG013038 , AG022241 , RR00051