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Sedentary Aging is Associated with a Senescent Endothelial Cell Phenotype that is Ameliorated by Habitual Aerobic Exercise
Author(s) -
Donato Anthony J,
Chiang Rhea,
Pierce Gary L,
Lawson Brooke R,
Seals Douglas R
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.965.15
Subject(s) - senescence , telomerase , medicine , endocrinology , telomere , aerobic exercise , longevity , endothelial dysfunction , phenotype , endothelium , endothelial stem cell , biology , gerontology , in vitro , genetics , dna , gene
Replicative senescence is used in culture as a model of vascular endothelial aging. However, the relevance to in vivo aging in humans and the influence of lifestyle factors such as habitual exercise are unknown. To gain insight, endothelial cells (EC) were extracted from the brachial arteries of young (YS: n=10; 24±1yr) and older (OS: n=18; 62±1yr) sedentary and older habitually exercising (OE: n=6; 62±1yr) healthy adults. Compared with YS, OS had larger EC size (10,072±317 vs. 9031±306 pxls, P<0.05), greater p53 protein expression (0.57±0.02 vs. 0.45±0.03 p53/HUVEC intensity, P<0.05, quantitative immunofluorescence), a transcription factor related to increased cell senescence, and lower expression of both nuclear hTERT (0.43±0.05 vs. 0.60±0.09 NhTERT/HUVEC intensity, P < 0.05), a measure of telomerase activity, and SIRT‐1 (0.41±0.03 vs. 0.52±0.05 SIRT‐1/ HUVEC intensity, P<0.05), a deacetylase linked to enhanced longevity. EC from OE more closely resembled those from YS, featuring smaller EC size (9075± 309, P<0.05), lower p53 (0.37±0.04, P<0.01) and greater NhTERT (0.60±0.08, P<0.05) vs. OS, although SIRT‐1 expression was not different (P=0.15). Our results indicate that sedentary, but not physically active, aging in humans is associated with development of a senescent vascular EC phenotype. Prevention of vascular endothelial senescence may be an important mechanism by which regular exercise protects against age‐related cardiovascular diseases. NIH AG013038 , AG022241 , AG006537 , AG029337 , AG000279 , RR00051