Skip to main content

Advertisement

SpringerLink
Log in

Serum levels of cathepsin D, sirtuin1, and endothelial nitric oxide synthase are correlatively reduced in elderly healthy people

  • Original Article
  • Published:
Aging Clinical and Experimental Research Aims and scope Submit manuscript

Abstract

Aim

Nowadays, cathepsins have been reported to be related to aging. The aim of this study is to evaluate the association between serum levels of cathepsin D (CTSD) and human aging.

Methods

In the present study, we analyzed the serum levels of CTSD and its relation with levels of sirtuin1 (SIRT1) and endothelial nitric oxide synthase (eNOS) activity, which were known having an important role in aging. This study recruited 90 healthy subjects (62 men and 28 women), which were subdivided into three groups with respect to age: young (about 19 years old, n = 30), middle-age (about 40 years old, n = 30), and aged (above 65 years old, n = 30). Altered serum levels of CTSD and SIRT1 were measured by enzyme-linked immunosorbent assay, and eNOS activity was assessed by the conversion of 14C-l-arginine to 14C-L-citrulline.

Results

Elderly subjects had significantly lower CTSD, SIRT1, and eNOS than younger ones. Serum levels of CTSD were negatively correlated with age. There was a statistically significant positive correlation between serum levels of CTSD, eNOS, and SIRT1.

Conclusions

This study shows lower serum CTSD values in elderly subjects than in younger subjects. This is the first to demonstrate age-related changes in cathepsin D levels in humans and the association between SIRT1 and eNOS.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Okada R, Wu Z, Zhu A et al (2015) Cathepsin D deficiency induces oxidative damage in brain pericytes and impairs the blood-brain barrier. Mol Cell Neurosci 64:51–60. [Epub 2014 Dec 10]

    Article  CAS  PubMed  Google Scholar 

  2. Zhou JW, Cheng XR, Cheng JP et al (2012) The activity and mRNA expression of β-secretase, cathepsin D, and cathepsin B in the brain of senescence-accelerated mouse. J Alzheimers Dis 28:471–480

    CAS  PubMed  Google Scholar 

  3. Salminen A, Ojala J, Kaarniranta K et al (2012) Mitochondrial dysfunction and oxidative stress activate inflammasomes: impact on the aging process and age-related diseases. Cell Mol Life Sci 69:2999–3013

    Article  CAS  PubMed  Google Scholar 

  4. Lin Y, Epstein DL, Liton PB (2010) Intralysosomal iron induces lysosomal membrane permeabilization and cathepsin D-mediated cell death in trabecular meshwork cells exposed to oxidative stress. Invest Ophthalmol Vis Sci 51:6483–6495

    Article  PubMed  PubMed Central  Google Scholar 

  5. Luo XY, Qu SL, Tang ZH et al (2014) SIRT1 in cardiovascular aging. Clin Chim Acta 437:106–114

    Article  CAS  PubMed  Google Scholar 

  6. He W, Wang Y, Zhang M-Z et al (2010) Sirt1 activation protects the mouse renal medulla from oxidative injury. J Clin Investig 120:1056–1068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kao C-L, Chen L-K, Chang Y-L et al (2010) Resveratrol protects human endothelium from H2O2-induced oxidative stress and senescence via SirT1 activation. J Atheroscler Thromb 17:970–979

    Article  CAS  PubMed  Google Scholar 

  8. Fan H, Yang H-C, You L et al (2013) The histone deacetylase, SIRT1, contributes to the resistance of young mice to ischemia/reperfusion-induced acute kidney injury. Kidney Int 83:404–413

    Article  CAS  PubMed  Google Scholar 

  9. Kilic U, Gok O, Erenberk U et al (2015) A remarkable age-related increase in SIRT1 protein expression against oxidative stress in elderly: SIRT1 gene variants and longevity in human. PLoS One 10:e0117954

    Article  PubMed  PubMed Central  Google Scholar 

  10. Valerio A, Nisoli E (2015) Nitric oxide, interorganelle communication, and energy flow: a novel route to slow aging. Front Cell Dev Biol 3:6

    Article  PubMed  PubMed Central  Google Scholar 

  11. Zhong Y, Zhao J, Gu YJ et al (2015) Differential levels of cathepsin B and L in serum between young and aged healthy people and their association with matrix metalloproteinase 2. Arch Gerontol Geriatr 61:285–288

    Article  CAS  PubMed  Google Scholar 

  12. Hein TW, Singh U, Vasquez-Vivar J et al (2009) Human C-reactive protein induces endothelial dysfunction and uncoupling of eNOS in vivo. Atherosclerosis 206:61–68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zühlsdorf M, Imort M, Hasilik A et al (1983) Molecular forms of beta-hexosaminidase and cathepsin D in serum and urine of healthy subjects and patients with elevated activity of lysosomal enzymes. Biochem J 213:733–740

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kim HY, Lee M, Kang HW et al (2013) Cathepsin D levels are reduced in patients with preeclampsia in Korean population. Clin Biochem 46:1808–1811

    Article  CAS  PubMed  Google Scholar 

  15. Ozkayar N, Piskinpasa S, Akyel F et al (2015) Relation between serum cathepsin D levels and endothelial dysfunction in patients with chronic kidney disease. Nefrologia 35:72–79

    PubMed  Google Scholar 

  16. Piyanova A, Albayram O, Rossi CA et al (2013) Loss of CB1 receptors leads to decreased cathepsin D levels and accelerated lipofuscin accumulation in the hippocampus. Mech Ageing Dev 134:391–399

    Article  CAS  PubMed  Google Scholar 

  17. Coletta C, Módis K, Oláh G et al (2014) Endothelial dysfunction is a potential contributor to multiple organ failure and mortality in aged mice subjected to septic shock: preclinical studies in a murine model of cecal ligation and puncture. Crit Care 18:511

    Article  PubMed  PubMed Central  Google Scholar 

  18. Nisoli E, Tonello C, Cardile A et al (2005) Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310:314–317

    Article  CAS  PubMed  Google Scholar 

  19. Koka S, Aluri HS, Xi L et al (2014) Chronic inhibition of phosphodiesterase 5 with tadalafil attenuates mitochondrial dysfunction in type 2 diabetic hearts: potential role of NO/SIRT1/PGC-1alpha signaling. Am J Physiol Heart Circ Physiol 306:H1558–H1568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ota H, Akishita M, Akiyoshi T et al (2012) Testosterone deficiency accelerates neuronal and vascular aging of SAMP8 mice: protective role of eNOS and SIRT1. PLoS One 7:e29598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Xing J, Liu H, Yang H et al (2014) Upregulation of Unc-51-like kinase 1 by nitric oxide stabilizes SIRT1, independent of autophagy. PLoS One 9:e116165

    Article  PubMed  PubMed Central  Google Scholar 

  22. Poulose N, Raju R (2015) Sirtuin regulation in aging and injury. Biochim Biophys Acta 1852:2442–2455

    Article  CAS  PubMed  Google Scholar 

  23. Mills KF, Satoh A, Imai S (2008) Age-associated loss of sirt1-mediated enhancement of glucose-stimulated insulin secretion in beta cell-specific sirt1-overexpressing (besto) mice. Aging Cell 7:78–88

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Natural Science Fund (No: 81401158).

Author information

Authors and Affiliations

  1. Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, No. 600, Yi Shan Road, Shanghai, 200233, People’s Republic of China

    Yuan Zhong & Guo-Xiang Fu

  2. Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA

    Alex. F. Chen

  3. Shanghai Sixth People’s Hospital Jinshan Branch, No. 147 Health Road, Zhujing Town, Jinshan District, Shanghai, 201500, People’s Republic of China

    Jian Zhao & Ying-Jia Gu

Authors
  1. Yuan Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alex. F. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jian Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ying-Jia Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guo-Xiang Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guo-Xiang Fu.

Ethics declarations

Conflicts of interest

All authors certify that they have not had any financial and personal relationships with other people or organizations that could inappropriately influence or bias this work. There is no conflict of interest for any of the authors.

Ethical standard

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The protocol of the study was approved by the ethics committee of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital (Shanghai, China).

Informed consent

Each person gave informed consent to the procedure.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhong, Y., Chen, A.F., Zhao, J. et al. Serum levels of cathepsin D, sirtuin1, and endothelial nitric oxide synthase are correlatively reduced in elderly healthy people. Aging Clin Exp Res 28, 641–645 (2016). https://doi.org/10.1007/s40520-015-0472-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40520-015-0472-7

Keywords

Search

Navigation