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Cortisol is not associated with telomere shortening or chromosomal instability in human lymphocytes cultured under low and high folate conditions.

Bull C, Christensen H, Fenech M - PLoS ONE (2015)

Bottom Line: Cortisol was significantly associated with reduced cell division and growth and had an apparent protective effect on cell viability in the FA(low) conditions.Conclusions: Both chronic cortisol exposure, and folate deficiency, resulted in telomere elongation, however, the effect of cortisol was marginal relative to that of folate.Cortisol was not associated with increased chromosomal instability, but caused a significant reduction in cell division and growth.

View Article: PubMed Central - PubMed

Affiliation: Nutritional Genomics and DNA Damage Diagnostics Laboratory, CSIRO Animal, Food and Health Sciences, Adelaide, South Australia, Australia; Department of Microbiology & Immunology, School of Molecular & Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia.

ABSTRACT
Chronic psychological stress and nutritional deficiencies are factors that impact negatively on human health and disease risk. Chronic stress has been associated with accelerated leukocyte telomere shortening in numerous cohorts, however, a mechanistic link has proven elusive. This study tested the hypotheses that chronic exposure to the stress hormone, cortisol, causes telomere shortening and chromosome instability (CIN) in vitro, and that these effects would be further exacerbated by folate (vitamin B9) deficiency. Primary human lymphocytes were maintained in vitro for 12 days in medium containing either 25 nM folic acid (FA(low)) or 100 nM FA (FA(high)), together with either 0, 400, 1000 or 3500 nM cortisol. The interactive effects of cortisol and FA were examined by comparing telomere length (TL), biomarkers of DNA damage, and cytostasis. At day 12 TL was 5-17% longer in lymphocytes cultured in FA(low) conditions (mean ± SD;10.2% ± 1.6), compared with those in FA(high) medium (9.1% ± 1, p = 0.02). Refuting the hypothesis, TL was consistently greater in the presence of cortisol. The effect of FA deficiency on the frequency of DNA damage was significant for nucleoplasmic bridges, circular nuclei, micronuclei and nuclear buds, (p < 0.0001-0.001). The effect of cortisol, however, was negligible, only reaching statistical significance for the frequency of fused nuclei (p = 0.04). Cortisol was significantly associated with reduced cell division and growth and had an apparent protective effect on cell viability in the FA(low) conditions. Conclusions: Both chronic cortisol exposure, and folate deficiency, resulted in telomere elongation, however, the effect of cortisol was marginal relative to that of folate. Cortisol was not associated with increased chromosomal instability, but caused a significant reduction in cell division and growth. Together these results indicate that cortisol is not directly genotoxic and that the telomere shortening associated with increased psychological stress in vivo may not be explained by a direct effect of cortisol.

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Related in: MedlinePlus

Impact of cortisol on lymphocyte cell division following 12 days in low folic acid (FA) (25 nM) or high FA (100 nM) culture conditions.(A) Cell growth. (B-D) frequencies (per 500 total cells) of mononucleated cells (monos); (C) binucleated cells (BN); and (D) multinucleated cells (mulits). (E) Nuclear division index (NDI); (duplicate measures for N = 6 participants. Mean ± SEM. *p ≤ 0.05).
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pone.0119367.g003: Impact of cortisol on lymphocyte cell division following 12 days in low folic acid (FA) (25 nM) or high FA (100 nM) culture conditions.(A) Cell growth. (B-D) frequencies (per 500 total cells) of mononucleated cells (monos); (C) binucleated cells (BN); and (D) multinucleated cells (mulits). (E) Nuclear division index (NDI); (duplicate measures for N = 6 participants. Mean ± SEM. *p ≤ 0.05).

Mentions: The mean total number of viable cells recorded at day 12 was significantly higher in FA(high) (229 ± 31 x 106) compared with FA(low) cultures (86 ± 8 x 106) (p < 0.0001). In cort-containing cultures viable cell counts were 16–36% lower than the respective cort-free control (VC) (ns). At day 12 [FA], [cort] and their interaction were responsible for 53% (p < 0.0001), 3% (p = 0.4) and 2% (p = 0.5) of variance, respectively (Fig. 3A).


Cortisol is not associated with telomere shortening or chromosomal instability in human lymphocytes cultured under low and high folate conditions.

Bull C, Christensen H, Fenech M - PLoS ONE (2015)

Impact of cortisol on lymphocyte cell division following 12 days in low folic acid (FA) (25 nM) or high FA (100 nM) culture conditions.(A) Cell growth. (B-D) frequencies (per 500 total cells) of mononucleated cells (monos); (C) binucleated cells (BN); and (D) multinucleated cells (mulits). (E) Nuclear division index (NDI); (duplicate measures for N = 6 participants. Mean ± SEM. *p ≤ 0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4352017&req=5

pone.0119367.g003: Impact of cortisol on lymphocyte cell division following 12 days in low folic acid (FA) (25 nM) or high FA (100 nM) culture conditions.(A) Cell growth. (B-D) frequencies (per 500 total cells) of mononucleated cells (monos); (C) binucleated cells (BN); and (D) multinucleated cells (mulits). (E) Nuclear division index (NDI); (duplicate measures for N = 6 participants. Mean ± SEM. *p ≤ 0.05).
Mentions: The mean total number of viable cells recorded at day 12 was significantly higher in FA(high) (229 ± 31 x 106) compared with FA(low) cultures (86 ± 8 x 106) (p < 0.0001). In cort-containing cultures viable cell counts were 16–36% lower than the respective cort-free control (VC) (ns). At day 12 [FA], [cort] and their interaction were responsible for 53% (p < 0.0001), 3% (p = 0.4) and 2% (p = 0.5) of variance, respectively (Fig. 3A).

Bottom Line: Cortisol was significantly associated with reduced cell division and growth and had an apparent protective effect on cell viability in the FA(low) conditions.Conclusions: Both chronic cortisol exposure, and folate deficiency, resulted in telomere elongation, however, the effect of cortisol was marginal relative to that of folate.Cortisol was not associated with increased chromosomal instability, but caused a significant reduction in cell division and growth.

View Article: PubMed Central - PubMed

Affiliation: Nutritional Genomics and DNA Damage Diagnostics Laboratory, CSIRO Animal, Food and Health Sciences, Adelaide, South Australia, Australia; Department of Microbiology & Immunology, School of Molecular & Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia.

ABSTRACT
Chronic psychological stress and nutritional deficiencies are factors that impact negatively on human health and disease risk. Chronic stress has been associated with accelerated leukocyte telomere shortening in numerous cohorts, however, a mechanistic link has proven elusive. This study tested the hypotheses that chronic exposure to the stress hormone, cortisol, causes telomere shortening and chromosome instability (CIN) in vitro, and that these effects would be further exacerbated by folate (vitamin B9) deficiency. Primary human lymphocytes were maintained in vitro for 12 days in medium containing either 25 nM folic acid (FA(low)) or 100 nM FA (FA(high)), together with either 0, 400, 1000 or 3500 nM cortisol. The interactive effects of cortisol and FA were examined by comparing telomere length (TL), biomarkers of DNA damage, and cytostasis. At day 12 TL was 5-17% longer in lymphocytes cultured in FA(low) conditions (mean ± SD;10.2% ± 1.6), compared with those in FA(high) medium (9.1% ± 1, p = 0.02). Refuting the hypothesis, TL was consistently greater in the presence of cortisol. The effect of FA deficiency on the frequency of DNA damage was significant for nucleoplasmic bridges, circular nuclei, micronuclei and nuclear buds, (p < 0.0001-0.001). The effect of cortisol, however, was negligible, only reaching statistical significance for the frequency of fused nuclei (p = 0.04). Cortisol was significantly associated with reduced cell division and growth and had an apparent protective effect on cell viability in the FA(low) conditions. Conclusions: Both chronic cortisol exposure, and folate deficiency, resulted in telomere elongation, however, the effect of cortisol was marginal relative to that of folate. Cortisol was not associated with increased chromosomal instability, but caused a significant reduction in cell division and growth. Together these results indicate that cortisol is not directly genotoxic and that the telomere shortening associated with increased psychological stress in vivo may not be explained by a direct effect of cortisol.

Show MeSH
Related in: MedlinePlus