Skip to main content
SpringerLink
Log in

An Overview of the Molecular and Cellular Biomarkers of Aging

  • Chapter
  • First Online:
Biomarkers of Human Aging

Part of the book series: Healthy Ageing and Longevity ((HAL,volume 10))

Abstract

The pace of physiological aging differs much in individuals, thus the tools to measure it precisely are to be found. Every quantitative trait of the organism, which is known to change with age, may be used as a biomarker of aging, but consequently not all biomarkers are informative and valuable for diagnostic purposes. The present chapter contains a review of basic molecular and cellular biomarkers of aging which are subdivided into groups named after the main target (it may be a molecule, a signaling cascade (or molecular complex), an intracellular structure or its functions) which significant changes are measured during aging. The process of biomarkers’ evaluation is described in the review as well as the procedure of endophenotype evaluation. We also discussed the relationship between endophenotypes and biomarkers in the context of existing “omics” approach in biogerontology.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton JP, Athineos D, Kang TW, Lasitschka F, Andrulis M, Pascual G (2013) A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol 15(8):978–990

    Article  CAS  Google Scholar 

  • Akbarian S, Beeri MS, Haroutunian V (2013) Epigenetic determinants of healthy and diseased brain aging and cognition. JAMA Neurol 70(6):711–718

    Article  Google Scholar 

  • Ameling S, Kacprowski T, Chilukoti RK, Malsch C, Liebscher V, Suhre K, Pietzner M, Friedrich N, Homuth G, Hammer E, Völker U (2015) Associations of circulating plasma microRNAs with age, body mass index and sex in a population-based study. BMC Med Genomics 8(1):61

    Google Scholar 

  • Barazzoni R, Short KR, Nair KS (2000) Effects of aging on mitochondrial DNA copy number and cytochrome c oxidase gene expression in rat skeletal muscle, liver, and heart. J Biol Chem 275(5):3343–3347

    Article  CAS  Google Scholar 

  • Bekaert S, De Meyer T, Van Oostveldt P (2005) Telomere attrition as ageing biomarker. Anticancer Res 25(4):3011–3021

    CAS  PubMed  Google Scholar 

  • Bota DA, Van Remmen H, Davies KJ (2002) Modulation of Lon protease activity and aconitase turnover during aging and oxidative stress. FEBS Lett 532(1–2):103–106

    Article  CAS  Google Scholar 

  • Briel M, Ferreira-Gonzalez I, You JJ, Karanicolas PJ, Akl EA, Wu P, Blechacz B, Bassler D, Wei X, Sharman A, Whitt I (2009) Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis. BMJ 338:b92

    Article  Google Scholar 

  • Chaleckis R, Murakami I, Takada J, Kondoh H, Yanagida M (2016) Individual variability in human blood metabolites identifies age-related differences. Proc Natl Acad Sci 113(16):4252–4259

    Article  CAS  Google Scholar 

  • Codd V, Mangino M, van der Harst P, Braund PS, Kaiser M, Beveridge AJ, Rafelt S, Moore J, Nelson C, Soranzo N, Zhai G (2010) Common variants near TERC are associated with mean telomere length. Nat Genet 42(3):197–199

    Article  CAS  Google Scholar 

  • ElSharawy A, Keller A, Flachsbart F, Wendschlag A, Jacobs G, Kefer N, Brefort T, Leidinger P, Backes C, Meese E, Schreiber S (2012) Genome-wide miRNA signatures of human longevity. Aging Cell 11(4):607–616

    Article  CAS  Google Scholar 

  • Engelfriet PM, Jansen EH, Picavet HSJ, Dollé ME (2013) Biochemical markers of aging for longitudinal studies in humans. Epidemiol Rev 35(1):132–151

    Article  Google Scholar 

  • Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol Ser A Biomed Sci Med Sci 69(Suppl_1):S4–S9

    Article  Google Scholar 

  • Gombar S, Jung HJ, Dong F, Calder B, Atzmon G, Barzilai N, Tian XL, Pothof J, Hoeijmakers JH, Campisi J, Vijg J (2012) Comprehensive microRNA profiling in B-cells of human centenarians by massively parallel sequencing. BMC Genom 13(1):353

    Article  CAS  Google Scholar 

  • Gorisse L, Pietrement C, Vuiblet V, Schmelzer CE, Köhler M, Duca L, Debelle L, Fornès P, Jaisson S, Gillery P (2016) Protein carbamylation is a hallmark of aging. Proc Natl Acad Sci 113(5):1191–1196

    Article  CAS  Google Scholar 

  • Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160(4):636–645

    Article  Google Scholar 

  • Grammatikakis I, Panda AC, Abdelmohsen K, Gorospe M (2014) Long noncoding RNAs (lncRNAs) and the molecular hallmarks of aging. Aging (Albany NY) 6(12):992

    Article  Google Scholar 

  • Gregory ML, Burton VJ, Shapiro BK (2015) Developmental disabilities and metabolic disorders. In: Neurobiology of brain disorders, pp 18–41

    Google Scholar 

  • Hoffman JM, Lyu Y, Pletcher SD, Promislow DE (2017) Proteomics and metabolomics in ageing research: from biomarkers to systems biology. Essays Biochem 61(3):379–388

    Article  Google Scholar 

  • Hooten NN, Abdelmohsen K, Gorospe M, Ejiogu N, Zonderman AB, Evans MK (2010) microRNA expression patterns reveal differential expression of target genes with age. PLoS ONE 5(5):e10724

    Article  Google Scholar 

  • Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biol 14(10):3156

    Article  Google Scholar 

  • Huang J, Xie Y, Sun X, Zeh HJ III, Kang R, Lotze MT, Tang D (2015) DAMPs, ageing, and cancer: the ‘DAMP Hypothesis’. Ageing Res Rev 24:3–16

    Article  CAS  Google Scholar 

  • Jylhävä J, Kotipelto T, Raitala A, Jylhä M, Hervonen A, Hurme M (2011) Aging is associated with quantitative and qualitative changes in circulating cell-free DNA: the Vitality 90+ study. Mech Ageing Dev 132(1–2):20–26

    Article  Google Scholar 

  • Kaushik S, Cuervo AM (2015) Proteostasis and aging. Nat Med 21(12):1406–1415

    Article  CAS  Google Scholar 

  • Kim J, Kim KM, Noh JH, Yoon JH, Abdelmohsen K, Gorospe M (2016) Long noncoding RNAs in diseases of aging. Biochimica et Biophysica Acta (BBA)-Gene Regul Mech 1859(1):209–221

    Article  CAS  Google Scholar 

  • Kumar S, Vijayan M, Bhatti JS, Reddy PH (2017) MicroRNAs as peripheral biomarkers in aging and age-related diseases. In: Progress in molecular biology and translational science, vol 146, pp 47–94. Academic Press

    Google Scholar 

  • Labbadia J, Morimoto RI (2015) The biology of proteostasis in aging and disease. Annu Rev Biochem 84:435–464

    Article  CAS  Google Scholar 

  • Lewington S, Clarke R, Qizilbash N, Peto R, Collins R (2003) Age-specific relevance of usual blood pressure to vascular mortality. Lancet 361(9366):1391–1392

    Article  Google Scholar 

  • Li X, Khanna A, Li N, Wang E (2011) Circulatory miR-34a as an RNA-based, noninvasive biomarker for brain aging. Aging (Albany NY) 3(10):985–1002

    Article  CAS  Google Scholar 

  • Liu Z, Burgess S, Wang Z, Deng W, Chu X, Cai J, Zhu Y, Shi J, Xie X, Wang Y, Jin L (2017) Corrigendum: associations of triglyceride levels with longevity and frailty: a Mendelian randomization analysis. Sci Rep 7:43981

    Article  CAS  Google Scholar 

  • López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153(6):1194–1217

    Article  Google Scholar 

  • Marcourakis T, Camarini R, Kawamoto EM, Scorsi LR, Scavone C (2008) Peripheral biomarkers of oxidative stress in aging and Alzheimer’s disease. Dementia Neuropsychol 2(1):2–8

    Article  Google Scholar 

  • Mecocci P, MacGarvey U, Kaufman AE, Koontz D, Shoffner JM, Wallace DC, Beal MF (1993) Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain. Ann Neurol Off J Am Neurol Assoc Child Neurol Soc 34(4):609–616

    CAS  Google Scholar 

  • Meder B, Backes C, Haas J, Leidinger P, Stähler C, Großmann T, Vogel B, Frese K, Giannitsis E, Katus HA, Meese E (2014) Influence of the confounding factors age and sex on microRNA profiles from peripheral blood. Clin Chem 60(9):1200–1208

    Article  CAS  Google Scholar 

  • Montoliu I, Scherer M, Beguelin F, DaSilva L, Mari D, Salvioli S, Martin FPJ, Capri M, Bucci L, Ostan R, Garagnani P (2014) Serum profiling of healthy aging identifies phospho-and sphingolipid species as markers of human longevity. Aging (Albany NY) 6(1):9

    Article  CAS  Google Scholar 

  • Olivieri F, Capri M, Bonafè M, Morsiani C, Jung HJ, Spazzafumo L, Viña J, Suh Y (2017) Circulating miRNAs and miRNA shuttles as biomarkers: perspective trajectories of healthy and unhealthy aging. Mech Ageing Dev 165:162–170

    Article  CAS  Google Scholar 

  • Olivieri F, Spazzafumo L, Santini G, Lazzarini R, Albertini MC, Rippo MR, Galeazzi R, Abbatecola AM, Marcheselli F, Monti D, Ostan R (2012) Age-related differences in the expression of circulating microRNAs: miR-21 as a new circulating marker of inflammaging. Mech Ageing Dev 133(11–12):675–685

    Article  CAS  Google Scholar 

  • Peters MJ, Joehanes R, Pilling LC, Schurmann C, Conneely KN, Powell J, Reinmaa E, Sutphin GL, Zhernakova A, Schramm K, Wilson YA, Kobes S, Tukiainen T, Ramos YF, Göring HH, Fornage M, Liu Y, Gharib SA, Stranger BE, De Jager PL, Aviv A, Levy D, Murabito JM, Munson PJ, Huan T, Hofman A, Uitterlinden AG, Rivadeneira F, van Rooij J, Stolk L, Broer L, Verbiest MM, Jhamai M, Arp P, Metspalu A, Tserel L, Milani L, Samani NJ, Peterson P, Kasela S, Codd V, Peters A, Ward-Caviness CK, Herder C, Waldenberger M, Roden M, Singmann P, Zeilinger S, Illig T, Homuth G, Grabe HJ, Völzke H, Steil L, Kocher T, Murray A, Melzer D, Yaghootkar H, Bandinelli S, Moses EK, Kent JW, Curran JE, Johnson MP, Williams-Blangero S, Westra HJ, McRae AF, Smith JA, Kardia SL, Hovatta I, Perola M, Ripatti S, Salomaa V, Henders AK, Martin NG, Smith AK, Mehta D, Binder EB, Nylocks KM, Kennedy EM, Klengel T, Ding J, Suchy-Dicey AM, Enquobahrie DA, Brody J, Rotter JI, Chen YD, Houwing-Duistermaat J, Kloppenburg M, Slagboom PE, Helmer Q, den Hollander W, Bean S, Raj T, Bakhshi N, Wang QP, Oyston LJ, Psaty BM, Tracy RP, Montgomery GW, Turner ST, Blangero J, Meulenbelt I, Ressler KJ, Yang J, Franke L, Kettunen J, Visscher PM, Neely GG, Korstanje R, Hanson RL, Prokisch H, Ferrucci L, Esko T, Teumer A, van Meurs JB, Johnson AD (2015) The transcriptional landscape of age in human peripheral blood. Nat Commun 6:8570

    Article  CAS  Google Scholar 

  • Porter KA (1957) Effect of homologous bone marrow injections in X-irradiated rabbits. British J Exp Pathol 38(4):401

    CAS  Google Scholar 

  • Prospective Studies Collaboration (2007) Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. Lancet 370(9602):1829–1839

    Article  Google Scholar 

  • Putin E, Mamoshina P, Aliper A, Korzinkin M, Moskalev A, Kolosov A, Ostrovskiy A, Cantor C, Vijg J, Zhavoronkov A (2016) Deep biomarkers of human aging: application of deep neural networks to biomarker development. Aging (Albany NY) 8(5):1021–1030

    Article  CAS  Google Scholar 

  • Rübe CE, Fricke A, Widmann TA, Fürst T, Madry H, Pfreundschuh M, Rübe C (2011) Accumulation of DNA damage in hematopoietic stem and progenitor cells during human aging. PLoS ONE 6(3):e17487

    Article  Google Scholar 

  • Sanada F, Taniyama Y, Muratsu J, Otsu R, Shimizu H, Rakugi H, Morishita R (2018) Source of chronic inflammation in aging. Front Cardiovasc Med 5:12

    Article  Google Scholar 

  • Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S, Boekholdt SM, Khaw KT, Gudnason V (2007) Triglycerides and the risk of coronary heart disease: 10 158 incident cases among 262 525 participants in 29 Western prospective studies. Circulation 115(4):450–458

    Article  CAS  Google Scholar 

  • Schram MT, Euser SM, De Craen AJ, Witteman JC, Frölich M, Hofman A, Jolles J, Breteler MM, Westendorp RG (2007) Systemic markers of inflammation and cognitive decline in old age. J Am Geriatr Soc 55(5):708–716

    Article  Google Scholar 

  • Semba RD, Nicklett EJ, Ferrucci L (2010) Does accumulation of advanced glycation end products contribute to the aging phenotype? J Gerontol Ser A Biomed Sci Med Sci 65(9):963–975

    Article  Google Scholar 

  • Serna E, Gambini J, Borras C, Abdelaziz KM, Belenguer A, Sanchis P, Avellana JA, Rodriguez-Manas L, Vina J (2012) Centenarians, but not octogenarians, up-regulate the expression of microRNAs. Sci Rep 2:961

    Article  Google Scholar 

  • Sharpless NE, Sherr CJ (2015) Forging a signature of in vivo senescence. Nat Rev Cancer 15(7):397

    Article  CAS  Google Scholar 

  • Short KR, Bigelow ML, Kahl J, Singh R, Coenen-Schimke J, Raghavakaimal S, Nair KS (2005) Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci 102(15):5618–5623

    Article  CAS  Google Scholar 

  • Sohal RS (1991) Hydrogen peroxide production by mitochondria may be a biomarker of aging. Mech Ageing Dev 60(2):189–198

    Article  CAS  Google Scholar 

  • Stadtman ER (2006) Protein oxidation and aging. Free Radic Res 40(12):1250–1258

    Article  CAS  Google Scholar 

  • Tammen SA, Dolnikowski GG, Ausman LM, Liu Z, Kim KC, Friso S, Choi SW (2014) Aging alters hepatic DNA hydroxymethylation, as measured by liquid chromatography/mass spectrometry. J Cancer Prev 19(4):301–308

    Article  Google Scholar 

  • Tang B, Dean B, Thomas EA (2011) Disease-and age-related changes in histone acetylation at gene promoters in psychiatric disorders. Transl Psychiatry 1(12):e64

    Article  CAS  Google Scholar 

  • Zhang R, Wang Y, Ye K, Picard M, Gu Z (2017) Independent impacts of aging on mitochondrial DNA quantity and quality in humans. BMC Genom 18(1):890

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Biology of Komi Science Center of Ural Branch of Russian Academy of Sciences, Syktyvkar, Russian Federation

    I. A. Solovev, M. V. Shaposhnikov & Alexey Moskalev

  2. Department of Ecology, Institute of Natural Sciences, Syktyvkar State University, Syktyvkar, Russian Federation

    I. A. Solovev & Alexey Moskalev

  3. Moscow Institute of Physics and Technology, Dolgoprudny, Russian Federation

    Alexey Moskalev

  4. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation

    Alexey Moskalev

Authors
  1. I. A. Solovev
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. V. Shaposhnikov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexey Moskalev
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. A. Solovev .

Editor information

Editors and Affiliations

  1. Laboratory of Geroprotective and Radioprotective Technologies, Institute of Biology, Komi Science Center of RAS, Syktyvkar, Komi Republic, Russia

    Alexey Moskalev

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Solovev, I.A., Shaposhnikov, M.V., Moskalev, A. (2019). An Overview of the Molecular and Cellular Biomarkers of Aging. In: Moskalev, A. (eds) Biomarkers of Human Aging. Healthy Ageing and Longevity, vol 10. Springer, Cham. https://doi.org/10.1007/978-3-030-24970-0_6

Download citation

Publish with us

Policies and ethics

Search

Navigation