Login Register Cart 0
Generic placeholder image

Current Aging Science

Editor-in-Chief

ISSN (Print): 1874-6098
ISSN (Online): 1874-6128

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Mitochondrial Common Deletion Level in Blood: New Insight Into the Effects of Age and Body Mass Index

Author(s): Mahboube Ahmadi, Masoud Golalipour* and Nader M. Samaei

Volume 11, Issue 4, 2018

Page: [250 - 254] Pages: 5

DOI: 10.2174/1874609812666190201163421

Abstract

Background: Age-related decrease in mitochondrial activity has been reported in several tissues. Reactive Oxygen Species (ROS) produced from defected mitochondria lead to aging and accumulate through time. However, studies about the mitochondrial DNA mutation level in blood are contradictory. Other lifestyle factors may modify the effects of age in post-mitotic tissues such as blood. The BMI represents the sum of the various lifestyle factors.

Objective: We proposed that age, obesity and mtDNA deletion are three ROS producing factors, which may interact with each other and induce senescence.

Methods: In a cross-sectional study, 172 male and female volunteers without known mitochondrial diseases were selected and the presence of common mitochondrial 4977bp deletion (ΔmtDNA4977) evaluated using Nested-PCR.

Results: Our results showed that a high percentage of samples (54.06%) harbor common deletion in blood. Furthermore, both BMI and the ΔmtDNA4977 levels significantly decrease with age. The chronological age, BMI and ΔmtDNA4977 reciprocally affect each other.

Conclusion: Our data suggest that age affects purifying selection and BMI, which may influence the relative level of the mtDNA common deletion in blood.

Keywords: Aging, mitochondrial common deletion, BMI, ROS, Nested-PCR, mtDNA.

« Previous Next »
Graphical Abstract

[1]
Greco M, Villani G, Mazzucchelli F, et al. Marked aging-related decline in efficiency of oxidative phosphorylation in human skin fibroblasts. FASEB J Off Publ Fed Am Soc Exp Biol 2003; 17: 1706-8.
[2]
Short KR, Bigelow ML, Kahl J, et al. Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci USA 2005; 102: 5618-23.
[3]
Lesnefsky EJ, Hoppel CL. Oxidative phosphorylation and aging. Ageing Res Rev 2006; 5: 402-33.
[4]
Sugiyama S, Takasawa M, Hayakawa M, et al. Changes in skeletal muscle, heart and liver mitochondrial electron transport activities in rats and dogs of various ages. Biochem Mol Biol Int 1993; 30: 937-44.
[5]
Trifunovic A, Wredenberg A, Falkenberg M, et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 2004; 429: 417-23.
[6]
Kujoth GC, Hiona A, Pugh TD, et al. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 2005; 309: 481-4.
[7]
Dumont P, Burton M, Chen QM, et al. Induction of replicative senescence biomarkers by sublethal oxidative stresses in normal human fibroblast. Free Radic Biol Med 2000; 28: 361-73.
[8]
Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev 1998; 78: 547-81.
[9]
Hayashi J, Ohta S, Kikuchi A, et al. Introduction of disease-related mitochondrial DNA deletions into HeLa cells lacking mitochondrial DNA results in mitochondrial dysfunction. Proc Natl Acad Sci USA 1991; 88: 10614-8.
[10]
Wang Y, Li Y, He C, et al. Mitochondrial regulation of cardiac aging Biochim Biophys Acta Mol Basis Dis
[http://dx.doi.org/10.1016/j.bbadis.2018.12.008]
[11]
Khaidakov M, Heflich RH, Manjanatha MG, et al. Accumulation of point mutations in mitochondrial DNA of aging mice. Mutat Res 2003; 526: 1-7.
[12]
Samuels DC, Li C, Li B, et al. Recurrent tissue-specific mtDNA mutations are common in humans. PLoS Genet 2013; 9: e1003929.
[13]
Bua E, Johnson J, Herbst A, et al. Mitochondrial DNA-deletion mutations accumulate intracellularly to detrimental levels in aged human skeletal muscle fibers. Am J Hum Genet 2006; 79: 469-80.
[14]
Bender A, Krishnan KJ, Morris CM, et al. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 2006; 38: 515-7.
[15]
Kraytsberg Y, Kudryavtseva E, McKee AC, et al. Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nat Genet 2006; 38: 518-20.
[16]
Nie H, Shu H, Vartak R, et al. Mitochondrial common deletion, a potential biomarker for cancer occurrence, is selected against in cancer background: A meta-analysis of 38 studies. PLoS One 2013; 8: e67953.
[17]
Sato A, Nakada K, Shitara H, et al. Deletion-Mutant mtDNA increases in somatic tissues but decreases in female germ cells with age. Genetics 2007; 177: 2031-7.
[18]
Carelli V, La Morgia C. Clinical syndromes associated with mtDNA mutations: Where we stand after 30 years. Essays Biochem 2018; 62: 235-54.
[19]
Larsson NG, Holme E. Multiple short direct repeats associated with single mtDNA deletions. Biochim Biophys Acta 1992; 1139: 311-4.
[20]
Meissner C, Bruse P, Mohamed SA, et al. The 4977 bp deletion of mitochondrial DNA in human skeletal muscle, heart and different areas of the brain: A useful biomarker or more? Exp Gerontol 2008; 43: 645-52.
[21]
Furukawa S, Fujita T, Shimabukuro M, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004; 114: 1752-61.
[22]
Matsuda M, Shimomura I. Increased oxidative stress in obesity: Implications for metabolic syndrome, diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Obes Res Clin Pract 2013; 7: e330-41.
[23]
Harman D. Aging: A theory based on free radical and radiation chemistry. J Gerontol 1956; 11: 298-300.
[24]
Cottrell DA, Blakely EL, Johnson MA, et al. Cytochrome c oxidase deficient cells accumulate in the hippocampus and choroid plexus with age. Neurobiol Aging 2001; 22: 265-72.
[25]
Mohamed SA, Hanke T, Erasmi AW, et al. Mitochondrial DNA deletions and the aging heart. Exp Gerontol 2006; 41: 508-17.
[26]
Gendron SP, Mallet JD, Bastien N, et al. Mitochondrial DNA common deletion in the human eye: A relation with corneal aging. Mech Ageing Dev 2012; 133: 68-74.
[27]
von Wurmb N, Oehmichen M, Meissner C. Demonstration of the 4977 bp deletion in human mitochondrial DNA from intravital and postmortem blood. Mutat Res 1998; 422: 247-54.
[28]
von Wurmb-Schwark N, Schwark T, Caliebe A, et al. Low level of the mtDNA(4977) deletion in blood of exceptionally old individuals. Mech Ageing Dev 2010; 131: 179-84.
[29]
Pavicic WH, Richard SM. Correlation analysis between mtDNA 4977-bp deletion and ageing. Mutat Res 2009; 670: 99-102.
[30]
Berneburg M, Gattermann N, Stege H, et al. Chronically ultraviolet-exposed human skin shows a higher mutation frequency of mitochondrial DNA as compared to unexposed skin and the hematopoietic system. Photochem Photobiol 1997; 66: 271-5.
[31]
Meissner C, Mohamed SA, Klueter H, et al. Quantification of mitochondrial DNA in human blood cells using an automated detection system. Forensic Sci Int 2000; 113: 109-12.
[32]
Mohamed SA, Wesch D, Blumenthal A, et al. Detection of the 4977 bp deletion of mitochondrial DNA in different human blood cells. Exp Gerontol 2004; 39: 181-8.
[33]
Zhang Y, Ma Y, Bu D, et al. Deletion of a 4977-bp Fragment in the mitochondrial genome is associated with mitochondrial disease severity. PLoS One 2015; 10: e0128624.
[34]
Wang P, Liu YL, Han L, et al. Mitochondria DNA 4977 bp common deletion in peripheral whole blood from healthy donors. Biomed Environ Sci BES 2013; 26: 990-3.
[35]
Iwai K, Iwamura Y, Yamashita S, et al. Effect of tea catechins on mitochondrial DNA 4977-bp deletions in human leucocytes. Mutat Res Mol Mech Mutagen 2006; 595: 191-5.
[36]
Cakir Y, Yang Z, Knight CA, et al. Effect of alcohol and tobacco smoke on mtDNA damage and atherogenesis. Free Radic Biol Med 2007; 43: 1279-88.
[37]
Štefan L, Čule M, Milinović I, et al. The Relationship between Lifestyle Factors and Body Compositionin Young Adults Int J Environ Res Public Health; 14 Epub ahead of print 8 August 2017
[http://dx.doi.org/10.3390/ijerph14080893]
[38]
Palozzi JM, Jeedigunta SP, Hurd TR. Mitochondrial DNA Purifying Selection in Mammals and Invertebrates. J Mol Biol 2018; 430: 4834-48.
[39]
Hernando-Rodríguez B, Artal-Sanz M. Mitochondrial quality control mechanisms and the phb (prohibitin) complex. Cells 2018; 7(12): E238.
[40]
Ni HM, Williams JA, Ding WX. Mitochondrial dynamics and mitochondrial quality control. Redox Biol 2015; 4: 6-13.

Rights & Permissions Print Cite
Article Metrics
36
5
© 2024 Bentham Science Publishers | Privacy Policy