Age-Dependent Telomere Shortening Is Slowed down by Enrichment of Intracellular Vitamin C via Suppression of Oxidative Stress
Abstract
Telomeres in eukaryotic somatic cells are destined to the age-dependent shortening, which has not been demonstrated to correlate to direct lesion of telomeric DNA by reactive oxygen intermediates (ROI); still less explicable is the inhibitory effect of ROI-scavenging on telomere shortening. Here, we succeeded in artificial slowdown of age-dependent telomere shortening to 52-62% of the untreated control, in human vascular endothelial cells, by addition of the oxidation-resistant type of ascorbic acid (Asc), Asc-2-O-phosphate (Asc2P), which concurrently achieved both extension of cellular life-span and prevention of cell size enlargement indicative of cellular senescence. The results are attributable to a 3.9-fold more marked enrichment of intracellular Asc (Asc(in)) by addition of Asc2P, subsequently dephosphorylated before or during transmembrane influx, than by addition of Asc itself, and also attributed to diminution of intracellular ROI to 53% of the control level by Asc2P; telomerase activity was at a trace level and underwent an age-dependent decline, which was significantly decelerated by Asc2P. Thus, age-dependent telomere-shortening can be decelerated by suppression of intracellular oxidative stress and/or by telomerase retention, both of which are achieved by enriched Asc(in) but not by extracellular Asc overwhelmingly more abundant than Asc(in).
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Ascorbic acid extends replicative lifespan of human embryonic fibroblasts by restoring age-related decline of mitochondrial function and lowering cellular ROS, therefore reducing mitochondrial and DNA damages with decelerated telomere shortening.
“For example, AA has been reported to extend replicative lifespan of human embryonic fibroblasts by restoring age-related decline of mitochondrial function and lowering cellular ROS, therefore reducing mitochondrial and DNA damages with decelerated telomere shortening [123,124].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [124]
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- Authors
- Furumoto, K., Inoue, E., Nagao, N., Hiyama, E., & Miwa, N.
- Affiliations
- Prefectural University of Hiroshima (JP)
- Hiroshima University (JP)
- Corresponding author
- Miwa, Nobuhiko
- Venue
- Life Sciences
- Publisher
- Elsevier BV
- Published
- 1998-08
- Volume
- 63
- Issue
- 11
- Pages
- 935-948
- ISSN
- 0024-3205 (ISSN-L)
- OpenAlex
- W2120926079
- Cited by
- 240
- References
- 18
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 10 · 2022: 8 · 2021: 6 · 2020: 3 · 2019: 9 · 2018: 9 · 2017: 7 · 2016: 5 · 2015: 9 · 2014: 10 · 2013: 7 · 2012: 12
- FWCI
- 4.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Life Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- telomere shortening, vitamin C, ascorbic acid 2-phosphate, oxidative stress, reactive oxygen species, cellular senescence, telomerase activity, vascular endothelial cells, cell lifespan
- MeSH terms
- Ascorbic Acid, Cells, Cultured, Endothelium, Vascular, Humans, Intracellular Fluid, Umbilical Veins, Telomere, Cellular Senescence, Oxidative Stress, Telomerase
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