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Accelerated aging as evidenced by increased telomere shortening and mitochondrial DNA depletion in patients with type 2 diabetes

Molecular and Cellular Biochemistry volume 365, pages 343–350 (2012)Cite this article

Abstract

Although shortened telomeres were shown associated with several risk factors of diabetes, there is lack of data on their relationship with mitochondrial dysfunction. Therefore, we compared the relationship between telomere length and mitochondrial DNA (mtDNA) content in patients with type 2 diabetes mellitus (T2DM; n = 145) and in subjects with normal glucose tolerance (NGT; n = 145). Subjects were randomly recruited from the Chennai Urban Rural Epidemiology Study. mtDNA content and telomere length were assessed by Real-Time PCR. Malonodialdehyde, a marker of lipid peroxidation was measured by thiobarbituric acid reactive substances (TBARS) using fluorescence methodology. Adiponectin levels were measured by radioimmunoassay. Oxidative stress as determined by lipid peroxidation (TBARS) was significantly (p < 0.001) higher in patients with T2DM compared to NGT subjects. In contrast, the mean telomere length, adiponectin and mtDNA content were significantly (p < 0.001) lower in patients with T2DM compared to NGT subjects. Telomere length was positively correlated with adiponectin, HDL, mtDNA content and good glycemic/lipid control and negatively correlated with adiposity and insulin resistance. On regression analysis, shortened telomeres showed significant association with T2DM even after adjusting for waist circumference, insulin resistance, triglyceride, HDL, adiponectin, mtDNA & TBARS. mtDNA depletion showed significant association with T2DM after adjusting for waist circumference and adiponectin but lost its significance when further adjusted for telomere length, TBARS and insulin resistance. Our study emphasizes the clustering of accelerated aging features viz., shortened telomeres, decreased mtDNA content, hypoadiponectinemia, low HDL, and increased oxidative stress in Asian Indian type 2 diabetes patients.

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Acknowledgments

Authors thank the Department of Biotechnology (DBT), New Delhi for the financial assistance. A senior research fellowship from the Council of Scientific and Industrial Research (CSIR), New Delhi is also thankfully acknowledged. This is the 123rd publication of CURES (CURES—123).

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Affiliations

  1. Department of Cell and Molecular Biology, Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control, IDF Centre of Education, Gopalapuram, Chennai, 600 086, Tamilnadu, India

    Finny Monickaraj, Sankaramoorthy Aravind, Kuppan Gokulakrishnan, Chandrakumar Sathishkumar, Paramasivam Prabu, Durai Prabu, Viswanathan Mohan & Muthuswamy Balasubramanyam

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  1. Finny Monickaraj
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  2. Sankaramoorthy Aravind
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  3. Kuppan Gokulakrishnan
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  8. Muthuswamy Balasubramanyam
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Correspondence to Muthuswamy Balasubramanyam.

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Monickaraj, F., Aravind, S., Gokulakrishnan, K. et al. Accelerated aging as evidenced by increased telomere shortening and mitochondrial DNA depletion in patients with type 2 diabetes. Mol Cell Biochem 365, 343–350 (2012). https://doi.org/10.1007/s11010-012-1276-0

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  • DOI: https://doi.org/10.1007/s11010-012-1276-0

Keywords

  • Telomere shortening
  • mtDNA depletion
  • Oxidative stress
  • Type 2 diabetes