Skip to main content
Log in

Dynamic changes in p66Shc mRNA expression in peripheral blood mononuclear cells following resistance training intervention in old frail women born to obese mothers: a pilot study

  • Short Communication
  • Published:
Aging Clinical and Experimental Research Aims and scope Submit manuscript

Abstract

The p66Shc gerontogene may affect healthspan by promoting fat accumulation. We assessed changes of p66Shc-mRNA in peripheral tissues in relation to maternal obesity and the moderating effects of resistance-training (RT) exercise in elderly frail women. Thirty-seven women participated in a 4-month RT program. Twenty were offspring of lean/normal weight mothers and 17 were offspring of overweight/obese mothers (OOM). P66Shc was assessed in peripheral blood mononuclear cells (PBMC) and in subcutaneous adipose tissue (SAT) before and after RT. Overall, OOM showed elevated p66Shc mRNA levels in the PBMC. Independently from maternal obesity, following RT there was a decrease in p66Shc expression in PBMC but not in SAT, particularly in subjects with a high body mass index. Results suggest that maternal obesity has long-term effects on the expression of genes involved in mitochondrial function and fat deposition and that RT modifies p66Shc expression in PBMC with greater effects in obese subjects.

ClinicalTrials.gov ID: NCT01931540.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  1. Barker DJ (1995) Intrauterine programming of adult disease. Mol Med Today 1:418–423

    Article  PubMed  CAS  Google Scholar 

  2. Iozzo P, Holmes M, Schmidt MV et al (2014) Developmental origins of healthy and unhealthy ageing: the role of maternal obesity—introduction to DORIAN. Obes Facts 7:130–151. doi:10.1159/000362656

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Ranieri SC, Fusco S, Pani G (2013) p66(ShcA): linking mammalian longevity with obesity-induced insulin resistance. Vitam Horm 91:219–241. doi:10.1016/b978-0-12-407766-9.00009-2

    Article  PubMed  CAS  Google Scholar 

  4. Berniakovich I, Trinei M, Stendardo M et al (2008) p66Shc-generated oxidative signal promotes fat accumulation. J Biol Chem 283:34283–34293. doi:10.1074/jbc.M804362200

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Berry A, Cirulli F (2013) The p66(Shc) gene paves the way for healthspan: evolutionary and mechanistic perspectives. Neurosci Biobehav Rev 37:790–802. doi:10.1016/j.neubiorev.2013.03.005

    Article  PubMed  CAS  Google Scholar 

  6. Pagnin E, Fadini G, de Toni R et al (2005) Diabetes induces p66shc gene expression in human peripheral blood mononuclear cells: relationship to oxidative stress. J Clin Endocrinol Metab 90:1130–1136. doi:10.1210/jc.2004-1283

    Article  PubMed  CAS  Google Scholar 

  7. Fox CS, Liu Y, White CC et al (2012) Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. PLoS Genet 8:e1002695. doi:10.1371/journal.pgen.1002695

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Scuteri A, Orru M, Morrell CH et al (2012) Associations of large artery structure and function with adiposity: effects of age, gender, and hypertension. The SardiNIA Study. Atherosclerosis 221:189–197. doi:10.1016/j.atherosclerosis.2011.11.045

    Article  PubMed  CAS  Google Scholar 

  9. Eriksson JG, Sandboge S, Salonen MK et al (2014) Long-term consequences of maternal overweight in pregnancy on offspring later health: findings from the Helsinki Birth Cohort Study. Ann Med 46:434–438. doi:10.3109/07853890.2014.919728

    Article  PubMed  Google Scholar 

  10. Bucci M, Huovinen V, Guzzardi MA et al (2016) Resistance training improves skeletal muscle insulin sensitivity in elderly offspring of overweight and obese mothers. Diabetologia 59:77–86. doi:10.1007/s00125-015-3780-8

    Article  PubMed  CAS  Google Scholar 

  11. Honka MJ, Bucci M, Andersson J et al (2016) Resistance training enhances insulin suppression of endogenous glucose production in elderly women. J Appl Physiol (1985) 120:633–639. doi:10.1152/japplphysiol.00950.2015

    Article  CAS  Google Scholar 

  12. Fuss IJ, Kanof ME, Smith PD et al (2009) Isolation of whole mononuclear cells from peripheral blood and cord blood. In: Current Protocols in Immunology, chap 7, unit 7. John Wiley & Sons, Inc. doi:10.1002/0471142735.im0701s85

  13. Giorgio M, Migliaccio E, Orsini F et al (2005) Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis. Cell 122:221–233. doi:10.1016/j.cell.2005.05.011

    Article  PubMed  CAS  Google Scholar 

  14. Trinei M, Berniakovich I, Beltrami E et al (2009) P66Shc signals to age. Aging 1:503–510. doi:10.18632/aging.100057

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Granatiero V, Gherardi G, Vianello M et al (2017) Role of p66shc in skeletal muscle function. Sci Rep 7:6283. doi:10.1038/s41598-017-06363-0

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Perrini S, Tortosa F, Natalicchio A et al (2015) The p66Shc protein controls redox signaling and oxidation-dependent DNA damage in human liver cells. Am J Physiol Gastrointest Liver Physiol 309:G826–G840. doi:10.1152/ajpgi.00041.2015

    Article  PubMed  CAS  Google Scholar 

  17. Paneni F, Mocharla P, Akhmedov A et al (2012) Gene silencing of the mitochondrial adaptor p66(Shc) suppresses vascular hyperglycemic memory in diabetes. Circ Res 111:278–289. doi:10.1161/CIRCRESAHA.112.266593

    Article  PubMed  CAS  Google Scholar 

  18. Ciciliot S, Albiero M, Menegazzo L et al (2015) p66Shc deletion or deficiency protects from obesity but not metabolic dysfunction in mice and humans. Diabetologia 58:2352–2360. doi:10.1007/s00125-015-3667-8

    Article  PubMed  CAS  Google Scholar 

  19. Finelli C, Sommella L, Gioia S et al (2013) Should visceral fat be reduced to increase longevity? Ageing Res Rev 12:996–1004. doi:10.1016/j.arr.2013.05.007

    Article  PubMed  Google Scholar 

  20. Caprari P, Scuteri A, Salvati AM et al (1999) Aging and red blood cell membrane: a study of centenarians. Exp Gerontol 34:47–57

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The study was conducted within the EU-funded project “Developmental Origins of Healthy and Unhealthy Ageing: The Role of Maternal Obesity” (FP7-HEALTH-DORIAN, G.A. 278603), and the Finnish Centre of Excellence in Molecular Imaging in Cardiovascular and Metabolic Research, supported by the Academy of Finland, University of Turku, Turku University Hospital and Åbo Akademi University. We thank M. Trinei, M. Giorgio and P.G. Pelicci at European Institute for Oncology, Milan, Italy, for providing the p66Shc primers and Silvia Poggini for graphical help.

Author information

Authors and Affiliations

Authors

Contributions

AB analyzed all p66Shc data, conducted the statistical analysis, interpreted the results and drafted the article; MB and VH collected PBMC and SAT samples and drafted the article CR analyzed all PBMC and SAT samples; MAG helped with interpretation of the data and drafted the article; FC, PI, JGE and PN made substantial contributions to the conception, design and coordination of the study and to interpretation of the data, and drafted the article. All authors revised the article critically for important intellectual content and approved the final version to be published. AB and FC are the guarantors of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to Alessandra Berry.

Ethics declarations

Funding

European Commission under the FP7 (Project DORIAN—Developmental ORIgins of healthy and unhealthy AgeiNg: The role of maternal obesity—Grant Agreement no. 278603) and H2020 AwE “Ageing with Elegans” (Grant Agreement no. 633589).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was conducted according to the principles of Declaration of Helsinki 1964 and and its later amendments and was approved by the Ethics Committee of the Hospital District of South-West Finland.

Informed consent

All participants gave written informed consent.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Berry, A., Bucci, M., Raggi, C. et al. Dynamic changes in p66Shc mRNA expression in peripheral blood mononuclear cells following resistance training intervention in old frail women born to obese mothers: a pilot study. Aging Clin Exp Res 30, 871–876 (2018). https://doi.org/10.1007/s40520-017-0834-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40520-017-0834-4

Keywords

Navigation