Journal article
Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function
American journal of physiology. Heart and circulatory physiology, Vol.313(5), pp.H890-H895
11/01/2017
DOI: 10.1152/ajpheart.00416.2017
PMCID: PMC5792201
PMID: 28971843
Abstract
Cellular senescence is emerging as a key mechanism of age-related vascular endothelial dysfunction, but evidence in healthy humans is lacking. Moreover, the influence of lifestyle factors such as habitual exercise on endothelial cell (EC) senescence is unknown. We tested the hypothesis that EC senescence increases with sedentary, but not physically active, aging and is associated with vascular endothelial dysfunction. Protein expression (quantitative immunofluorescence) of p53, a transcription factor related to increased cellular senescence, and the cyclin-dependent kinase inhibitors p21 and p16 were 116%, 119%, and 128% greater (all
< 0.05), respectively, in ECs obtained from antecubital veins of older sedentary (60 ± 1 yr,
= 12) versus young sedentary (22 ± 1 yr,
= 9) adults. These age-related differences were not present (all
> 0.05) in venous ECs from older exercising adults (57 ± 1 yr,
= 13). Furthermore, venous EC protein levels of p53 (
= -0.49,
= 0.003), p21 (
= -0.38,
= 0.03), and p16 (
= -0.58,
= 0.002) were inversely associated with vascular endothelial function (brachial artery flow-mediated dilation). Similarly, protein expression of p53 and p21 was 26% and 23% higher (both
< 0.05), respectively, in ECs sampled from brachial arteries of healthy older sedentary (63 ± 1 yr,
= 18) versus young sedentary (25 ± 1 yr,
= 9) adults; age-related changes in arterial EC p53 and p21 expression were not observed (
> 0.05) in older habitually exercising adults (59 ± 1 yr,
= 14). These data indicate that EC senescence is associated with sedentary aging and is linked to endothelial dysfunction. Moreover, these data suggest that prevention of EC senescence may be one mechanism by which aerobic exercise protects against endothelial dysfunction with age.
Our study provides novel evidence in humans of increased endothelial cell senescence with sedentary aging, which is associated with impaired vascular endothelial function. Furthermore, our data suggest an absence of age-related increases in endothelial cell senescence in older exercising adults, which is linked with preserved vascular endothelial function.
Details
- Title: Subtitle
- Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function
- Creators
- Matthew J Rossman - Integrative Physiology, University of Colorado Boulder, Boulder, Colorado; matthew.rossman@colorado.eduRachelle E Kaplon - Integrative Physiology, University of Colorado Boulder, Boulder, ColoradoSierra D Hill - Integrative Physiology, University of Colorado Boulder, Boulder, ColoradoMolly N McNamara - Integrative Physiology, University of Colorado Boulder, Boulder, ColoradoJessica R Santos-Parker - Integrative Physiology, University of Colorado Boulder, Boulder, ColoradoGary L Pierce - Health and Human Physiology, University of Iowa, Iowa City, Iowa; andDouglas R Seals - Integrative Physiology, University of Colorado Boulder, Boulder, ColoradoAnthony J Donato - Internal Medicine, University of Utah, Salt Lake City, Utah
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.313(5), pp.H890-H895
- Publisher
- United States
- DOI
- 10.1152/ajpheart.00416.2017
- PMID
- 28971843
- PMCID
- PMC5792201
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Grant note
- K02 AG045339 / NIA NIH HHS R01 AG050238 / NIA NIH HHS R44 AG053131 / NIA NIH HHS
- Language
- English
- Date published
- 11/01/2017
- Academic Unit
- Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984002328502771
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