Skip to main content
SpringerLink
Log in

Biomarkers of chondriome topology and function: implications for the extension of healthy aging

  • Research Article
  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

Multiple theories of aging (e.g., free radical, error catastrophe, mitochondrial) are complementary but fail to provide adequate models that comprehensively predict lifelong aging processes and that are valid across species. Hayflick (PLoS Genet 3(12):2351–2354, 2007) described six universal characteristics of aging that focus upon post-reproductive molecular entropy. Here we present a thermodynamic potential model of aging in which the energetic and topological properties of the mitochondrion drive functional and structural stabilities within living systems. Using multivariate regressions of physiological assessments from the National Health and Nutrition Examination Survey, VO2 max consistently declined with age regardless of gender or race, although it had a significantly greater decline for African American females. Percent fat (negative), hematocrit (negative), and urine creatinine (negative) were strongly and significantly associated with VO2 max and male aging, although cholesterol (positive) was an additional factor for African American males. Bioenergetic measures such as VO2 max can be useful for physical assessments to promote healthy aging.

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
Fig. 3

Similar content being viewed by others

References

  • Adelman JS, Martin LB (2009) Vertebrate sickness behaviors: adaptive and integrated neuroendocrine immune responses. Integr Comp Biol 49(3):202–214

    Article  CAS  PubMed  Google Scholar 

  • Agutter PS, Tuszynski JA (2014) Analytical theories of allometric scaling. J Exp Biol 214:1055–1062

    Article  Google Scholar 

  • Aon MA, Cortassa S, O’Rourke B (2008) Mitochondrial oscillations in physiology and pathophysiology. Adv Exp Med Biol 641:98–117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ballal SA, Gallini CA, Segata N, Huttenhower C, Garrett WS (2011) Host and gut microbiota symbiotic factors: lessons from inflammatory bowel disease and successful symbionts. Cell Microbiol 13(4):508–517

    Article  CAS  PubMed  Google Scholar 

  • Besedovsky HO, Del Rey A (1996) Immune-neuro-endocrine interactions: facts and hypotheses. Endocr Rev 17(1):64–102

    Article  CAS  PubMed  Google Scholar 

  • Brink TC, Demetrius L, Lehrach H, Adjaye J (2009) Age-related transcriptional changes in gene expression in different organs of mice support the metabolic stability theory of aging. Biogerontology 10:549–564

    Article  CAS  PubMed  Google Scholar 

  • Brunk UT, Terman A (2002) The mitochondrial-lysosomal axis theory of aging: accumulation of damaged mitochondria as a result of imperfect autophagocytosis. Eur J Biochem 269:1996–2002

    Article  CAS  PubMed  Google Scholar 

  • Burkewtiz K, Zhang Y, Mair WB (2014) AMPK at the nexus of energetics and aging. Cell Metab 20(1):10–25

    Article  Google Scholar 

  • Butcher S, Chahel H, Lord JM (2000) Aging and the neutrophil: no appetite for killing? Immunology 100:411–416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen H, Chan DC (2004) Mitochondrial dynamics in mammals. Curr Top Dev Biol 59:119–144

    Article  CAS  PubMed  Google Scholar 

  • Cohen J (2002) The immunopathogenesis of sepsis. Nature 420:885–891

    Article  CAS  PubMed  Google Scholar 

  • Davies P, Demetrius LA, Tuszynski JA (2012) Implications of quantum metabolism and natural selection for the origin of cancer cells and tumor progression. AIP Adv 2:011101. doi:10.1063/1.3697850

    Article  PubMed Central  Google Scholar 

  • Demetrius L, Legendre S, Harremöes P (2009) Evolutionary entropy: a predictor of body size, metabolic rate and maximal life span. Bull Math Biol 71:800–818

    Article  PubMed  PubMed Central  Google Scholar 

  • Diaz F, Bayona-Bafaluy MP, Rana M, Mora M, Hao H, Moraes CT (2002) Human mitochondrial DNA with large deletions repopulates organelles faster than full-length genomes under relaxed copy number control. Nucl Acids Res 30(21):4626–4633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dinarello CA (2000) Proinflammatory cytokines. CHEST 118(2):503–508

    Article  CAS  PubMed  Google Scholar 

  • Dzbek J, Korzeniewski B (2008) Control over the contribution of the mitochondrial membrane potential (deltapsi) and proton gradient (deltapH) to the protonmotive force (deltap): in silico studies. J Biol Chem 283(48):33232–33239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA (2005) Diversity of the human intestinal microbial flora. Science 308(5728):1635–1638

    Article  PubMed  PubMed Central  Google Scholar 

  • Ferrari AU, Radaelli A, Centola M (2003) Invited review: aging and the cardiovascular system. J Appl Physiol 95:2591–2597

    Article  PubMed  Google Scholar 

  • Finkel T, Serrano M, Blasco MA (2007) The common biology of cancer and aging. Nature 448:767–774

    Article  CAS  PubMed  Google Scholar 

  • Gomes AP, Price NL, Ling AJY, Moslehi JJ, Montgomery MK, Rajman L, White JP, Teodoro JS, Wrann CD, Hubbard BP, Mercken EM, Palmeira CM, de Cabo R, Rolo AP, Turner N, Bell EL, Sinclair DA (2013) Declining NAD + induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 155(3):1624–1638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guarente L (2014a) Aging research—where do we stand and where are we going? Cell 159:15–19

    Article  CAS  PubMed  Google Scholar 

  • Guarente L (2014b) Linking DNA damage, NAD+/SIRT1, and aging. Cell Metab 20:706–707

    Article  CAS  PubMed  Google Scholar 

  • Hartman AL, Lough DM, Barupal DK, Fiehn O, Fishbein T, Zasloff M, Eisen JA (2009) Human gut microbiome adopts an alternative state following small bowel transplantation. Proc Natl Acad Sci USA 106(40):17187–17192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hayflick L (1968) Human cells and aging. Sci Am 218(3):32–37

    Article  CAS  PubMed  Google Scholar 

  • Hayflick L (1994) How and why we age. Ballantine, New York

    Google Scholar 

  • Hayflick L (2007) Entropy explains aging, genetic determinism explains longevity, and undefined terminology explains misunderstanding both. PLoS Genet 3(12):2351–2354

    Article  CAS  Google Scholar 

  • Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25(3):585–621

    Article  CAS  PubMed  Google Scholar 

  • Hollar D (2013) Cross-sectional patterns of allostatic load among persons with varying disabilities, NHANES: 2001-2010. Disabil Health J 6:177–187

    Article  PubMed  Google Scholar 

  • Hollar D (2016) Lifespan development, instability, and Waddington’s epigenetic landscape. In: Hollar D (ed) Epigenetics, the environment, and children’s health across lifespans. Springer, New York, pp 361–376

    Chapter  Google Scholar 

  • Hollar D, Lewis J (2015) Heart age differentials and general cardiovascular risk profiles for persons with varying disabilities: NHANES 2001-2010. Disabil Health J 8:51–60

    Article  PubMed  Google Scholar 

  • Huang P, Galloway CA, Yoon Y (2011) Control of mitochondrial morphology through differential interactions of mitochondrial fusion and fission proteins. PLoS ONE 6(5):e20655. doi:10.1371/journal.pone.0020655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Itoh K, Nakamura K, Iijima M, Sesaki H (2013) Mitochondrial dynamics in neurodegeneration. Trends Cell Biol 23(2):64–71

    Article  CAS  PubMed  Google Scholar 

  • Kenyon CJ (2010) The genetics of ageing. Nature 464:504–512

    Article  CAS  PubMed  Google Scholar 

  • Kleiber M (1932) Body size and metabolism. Hilgardia 6:315–353

    Article  CAS  Google Scholar 

  • Kolokotones T, Savage V, Deeds EJ, Fontana W (2010) Curvature in metabolic scaling. Nature 464:753–756

    Article  Google Scholar 

  • Kothapalli CR, Taylor PM, Smolenski RT, Yacoub MH, Ramamurthi A (2009) Transforming Growth Factor Beta 1 and hyaluronan oligomers synergistically enhance elastin matrix regeneration by vascular smooth muscle cells. Tissue Eng 15(3):501–511

    Article  CAS  Google Scholar 

  • Kumar V, Sharma A (2010) Neutrophils: cinderella of the innate immune system. Int Immunopharmacol 10:1325–1334

    Article  CAS  PubMed  Google Scholar 

  • Kurz FT, Aon MA, O’Rourke B, Armoundas AA (2010) Spatio-temporal oscillations of individual mitochondria in cardiac myocytes reveal modulation of synchronized mitochondrial clusters. Proc Natl Acad Sci USA 107(32):14315–14320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795

    Article  CAS  PubMed  Google Scholar 

  • Loe H, Rognmo Ø, Saltin B, Wisløff U (2013) Aerobic capacity reference data in 3816 healthy men and women 20-90 years. PLoS ONE 8(5):e64319. doi:10.1371/journal.pone.0064319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mannella CA, Pfeiffer DR, Bradshaw PC, Moraru II, Slepchenko B, Loew LM, Hsieh CE, Buttle K, Marko M (2001) Topology of the mitochondrial inner membrane: dynamics and bioenergetic implications. IUBMB Life 52:93–100

    Article  CAS  PubMed  Google Scholar 

  • Minocherhomji S, Tollefsbol TO, Singh KK (2012) Mitochondrial regulation of epigenetics and its role in human diseases. Epigenetics 7(4):326–334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Montero J, Mari M, Colell A, Morales A, Basañez G, Garcia-Ruiz C, Fernández-Checa JC (2010) Cholesterol and peroxidized cardiolipin in mitochondrial membrane properties, permeabilization and cell death. Biochim Biophys Acta 1797(6–7):1217–1224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murdock DG, Christacos NC, Wallace DC (2000) The age-related accumulation of a mitochondrial DNA control region mutation in muscle, but not brain, detected by a sensitive PNA-directed PCR clamping based method. Nucl Acids Res 28(21):4350–4355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • National Center for Health Statistics (2005) Analytic and reporting guidelines: the National Health and Nutrition Examination Survey (NHANES). National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville. www.cdc.gov/nchs/data/nhanes/nhanes_03_04/nhanes_analytic_guidelines_dec_2005.pdf. Accessed 12 Jan 2016

  • National Center for Health Statistics (2011) Analytic note regarding 2007-2010 survey design changes and combining data across other survey cycles. National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville. www.cdc.gov/nchs/data/nhanes/analyticnote_2007-2010.pdf; Accessed 12 Jan 2016

  • Nicholls DG, Budd SL (2000) Mitochondria and neuronal survival. Physiol Rev 80(1):315–360

    CAS  PubMed  Google Scholar 

  • Oka T, Hikoso S, Yamaguchi O, Taneike M, Takeda T, Tamai T, Oyabu J, Murakawa T, Nakayama H, Nishida K, Akira S, Yamamoto A, Komuro I, Otsu K (2012) Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature 485:251–255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perkins GA, Ellisman MH, Fox DA (2003) Three-dimensional analysis of mouse rod and cone mitochondrial cristae architecture: bioenergetics and functional implications. Mol Vis 9:60–73

    CAS  PubMed  Google Scholar 

  • Picard M, Shirihai OS, Gentil BJ, Burelle Y (2013) Mitochondrial morphology transitions and functions: implications for retrograde signaling? Am J Physiol Regul Integr Comp Physiol 304:R393–R406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pieczenik SR, Neustadt J (2007) Mitochondrial dysfunction and molecular pathways of disease. Exp Mol Pathol 83:84–92

    Article  CAS  PubMed  Google Scholar 

  • Price NL, Gomes AP, Ling AJY, Duarte FV, Martin-Montalvo A, North BJ, Agarwal B, Ye L, Ramadori G, Teodoro JS, Hubbard BP, Varela AT, Davis JG, Varamini B, Hafner A, Moaddel R, Rolo AP, Coppari R, Palmeira CM, de Cabo R, Baur JA, Sinclair DA (2012) SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab 15(5):675–690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rice IM, Rice LA, Motl RW (2015) Promoting physical activity through a manual wheelchair propulsion intervention in persons with multiple sclerosis. Arch Phys Med Rehabil 96(10):1850–1858

    Article  PubMed  Google Scholar 

  • Rimmer JH, Rauworth AE, Wang EC, Nicola TL, Hill B (2009) A preliminary study to examine the effects of aerobic and therapeutic (nonaerobic) exercise on cardiorespiratory fitness and coronary risk reduction in stroke survivors. Arch Phys Med Rehabil 90(3):407–412

    Article  PubMed  Google Scholar 

  • Romanello V, Gguadagnin E, Gomes L, Roder I, Sandri C, Petersen Y, Milan G, Masiero E, Del Piccolo P, Foretz M, Scorrano L, Rudolf R, Sandri M (2010) Mitochondrial fission and remodeling contributes to muscle atrophy. EMBO J 29(10):1774–1785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seeman TE, McEwen BS, Rowe JW, Singer BH (2001) Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging. Proc Natl Acad Sci USA 98(8):4770–4775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seeman TE, Singer BH, Ryff CD, Love GD, Levy-Storms L (2002) Social relationships, gender, and allostatic load across two age cohorts. Psychosom Med 64:395–406

    Article  PubMed  Google Scholar 

  • Selye H (1950) Stress and the general adaptation syndrome. Br Med J 1(4667):1382–1392

    Article  Google Scholar 

  • Shaham O, Slate NG, Goldberger O, Xu Q, Ramanathan A, Souza AL, Clish CB, Sims KB, Mootha VK (2010) A plasma signature of human mitochondrial disease revealed through metabolic profiling of spent media from cultured muscle cells. Proc Natl Acad Sci USA 107(4):1571–1575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen EZ, Song CQ, Lin Y, Zhang WH, Su PF, Liu WY, Zhang P, Xu J, Lin N, Zhan C, Wang X, Shyr Y, Cheng H, Dong MQ (2014) Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans. Nature 508(7494):128–132

    Article  CAS  PubMed  Google Scholar 

  • Shvartz E, Reibold RC (1990) Aerobic fitness norms for males and females aged 6 to 75 years: a review. Aviat Space Environ Med 61(1):3–11

    CAS  PubMed  Google Scholar 

  • Stetler RA, Leak RK, Gao Y, Chen J (2013) The dynamics of the mitochondrial organelle as a potential therapeutic target. J Cereb Blood Flow Metab 33:22–32

    Article  Google Scholar 

  • Sukharov VM, Dikov D, Reichert AS, Meyer-Harmann M (2012) Emergence of the mitochondrial reticulum from fission and fusion dynamics. PLoS Comp Biol 8(10):e1002745. doi:10.1371/journal.pcbi.1002745

    Article  Google Scholar 

  • Tang HL, Lung HL, Wu KC, Le AHP, Tang HM, Chiu M (2008) Vimentin supports mitochondrial morphology and organization. Biochem J 410:141–146

    Article  CAS  PubMed  Google Scholar 

  • Terman A, Kurz T, Gustafsson B, Brunk UT (2008) The involvement of lysosomes in myocardial aging and disease. Curr Cardiol Rev 4:107–115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Terman A, Kurz T, Navratil M, Arriaga EA, Brunk UT (2010) Mitochondrial turnover and aging of long-lived postmitotic cells: the mitochondrial-lysosomal axis theory of aging. Antioxid Redox Signal 12:503–535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thar R, Kühl M (2004) Propagation of electromagnetic radiation in mitochondria? J Theor Biol 230:261–270

    Article  CAS  PubMed  Google Scholar 

  • Ueda T, Cheng G, Kuroki Y, Sano H, Sugiyama K, Motojima S, Fukuda T (2000) Effects of aging on surfactant forms in rats. Eur Respir J 15:80–84

    Article  CAS  PubMed  Google Scholar 

  • van Ingen Schenau GJ, de Groot G (1983) Differences in oxygen consumption and external power between male and female speed skaters during supramaximal cycling. Eur J Appl Physiol Occup Physiol 51(3):337–345

    Article  PubMed  Google Scholar 

  • Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324(5930):1029–1033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ventura N, Rea SL, Testi R (2006a) Long-lived C. elegans mitochondrial mutants as a model for human mitochondrial-associated diseases. Exp Gerontol 41:974–991

    Article  CAS  PubMed  Google Scholar 

  • Ventura N, Rea SL, Testi R (2006b) Long-lived C. elegans mitochondrial mutants as a model for human mitochondrial-associated diseases. Exp Gerontol 41:974–991

    Article  CAS  PubMed  Google Scholar 

  • Vijg J, Campisi J (2008) Puzzles, promises and a cure for ageing. Nature 454:1065–1071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wallace DC, Fan W (2010) Energetics, epigenetics, mitochondrial genetics. Mitochondrion 10(1):12–31

    Article  CAS  PubMed  Google Scholar 

  • Weibel ER, Hoppeler H (2005) Exercise-induced maximal metabolic rate scales with muscle aerobic capacity. J Exp Biol 208:1635–1644

    Article  PubMed  Google Scholar 

  • West GB, Brown JH (2005) The origin of allometric scaling laws in biology from genomes to ecosystems: towards a quantitative unifying theory of biological structure and organization. J Exp Biol 208:1575–1592

    Article  PubMed  Google Scholar 

  • West GB, Woodruff WH, Brown JH (2002) Allometric scaling of metabolic rate from molecules and mitochondria to cells and mammals. Proc Natl Acad Sci USA 99(suppl 1):2473–2478

    Article  PubMed  PubMed Central  Google Scholar 

  • Westermann B (2002) Merging mitochondria matters: cellular role and molecular machinery of mitochondrial fusion. EMBO Rep 3(6):527–531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wyss M, Kaddurah-Daouk R (2000) Creatine and creatinine metabolism. Physiol Rev 80(3):1107–1213

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Health Administration, Pfeiffer University, 2880 Slater Road, Suite 100, Morrisville, NC, 27560, USA

    David W. Hollar

Authors
  1. David W. Hollar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David W. Hollar.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hollar, D.W. Biomarkers of chondriome topology and function: implications for the extension of healthy aging. Biogerontology 18, 201–215 (2017). https://doi.org/10.1007/s10522-016-9673-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-016-9673-5

Keywords

Search

Navigation