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Circulating Biomarkers of Aging

  • Hongxia Zhang
  • Brian Wang
  • Kunlin JinEmail author
Chapter
Part of the Healthy Ageing and Longevity book series (HAL, volume 10)

Abstract

A major goal of geroscience is to achieve the ability to predict the rate of aging using biomarkers for the purpose of extending lifespan and healthspan. Chronological aging is not a suitable marker as it does not capture the true status of age-related changes. So far, there is no biomarker or combination of biomarkers that has emerged even though some have shown promise. In this chapter, we summarize novel cellular, protein, and DNA-related biomarkers for biological aging that can be found specifically in the circulation “for the life of every living thing is in the blood”.

Keywords

Aging Biomarkers Blood Lifespan Circulation MiRNA Protein Extracellular vesicles 

Abbreviation

AD

Alzheimer’s disease

APP

Amyloid precursor protein

AMAR

Apparent methylomic aging rate

AFR

Ascorbate free radical

B2M

Β2 microglobulin

BoA

Biomarker of aging

BBB

Blood-brain barrier

CR

Caloric restriction

CNS

Central nervous system

CSF

Cerebrospinal fluid

CAD

Coronary artery disease

DNA methylation

DNAm

DHA

Docosahexaenoic acid

ECs

Endothelial cells

EVs

Extracellular vesicles

FGFR

Fibroblast growth factor receptor

GDF

Growth differentiation factor

IDO

Indoleamine 2,3-dioxygenase enzyme

LTL

Leukocyte telomere length

OPCs

Oligodendrocyte progenitor cells

PBMCs

Peripheral blood mononuclear cells

ROS

Reactive oxygen species

RBCs

Red blood cells

rLTL

Relative leukocyte telomere length

rTL

Relative telomere length

SAA

Serum amyloid A

SORL1

Sortilin related receptor 1

SOD

Superoxide dismutase

TL

Telomere length

VCAM1

Vascular cell adhesion molecule 1

References

  1. Aberg MA, Aberg ND, Hedbacker H, Oscarsson J, Eriksson PS (2000) Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. J Neurosci 20:2896–2903PubMedCrossRefGoogle Scholar
  2. Ambros V (2001) microRNAs: tiny regulators with great potential. Cell 107:823–826PubMedCrossRefGoogle Scholar
  3. Andersen OM, Rudolph IM, Willnow TE (2016) Risk factor SORL1: from genetic association to functional validation in Alzheimer’s disease. Acta Neuropathologica 132:653–665.  https://doi.org/10.1007/s00401-016-1615-4CrossRefPubMedPubMedCentralGoogle Scholar
  4. Arguelles S, Venero JL, Garcia-Rodriguez S, Tomas-Camardiel M, Ayala A, Cano J, Machado A (2010) Use of haptoglobin and transthyretin as potential biomarkers for the preclinical diagnosis of Parkinson’s disease. Neurochem Int 57:227–234.  https://doi.org/10.1016/j.neuint.2010.05.014. S0197-0186(10)00183-X [pii]PubMedCrossRefGoogle Scholar
  5. Arraud N, Linares R, Tan S, Gounou C, Pasquet JM, Mornet S, Brisson AR (2014) Extracellular vesicles from blood plasma: determination of their morphology, size, phenotype and concentration. J Thromb Haemost JTH 12:614–627.  https://doi.org/10.1111/jth.12554PubMedCrossRefGoogle Scholar
  6. Arroyo JD et al (2011) Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A 108:5003–5008.  https://doi.org/10.1073/pnas.1019055108CrossRefGoogle Scholar
  7. Ashpole NM et al (2017) IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan. Geroscience 39:129–145.  https://doi.org/10.1007/s11357-017-9971-0PubMedPubMedCentralCrossRefGoogle Scholar
  8. Baek R, Varming K, Jorgensen MM (2016) Does smoking, age or gender affect the protein phenotype of extracellular vesicles in plasma? Transfus Apher Sci 55:44–52.  https://doi.org/10.1016/j.transci.2016.07.012PubMedCrossRefGoogle Scholar
  9. Balaj L, Lessard R, Dai L, Cho YJ, Pomeroy SL, Breakefield XO, Skog J (2011) Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat Commun 2:180.  https://doi.org/10.1038/ncomms1180
  10. Bari R et al (2011) Tetraspanins regulate the protrusive activities of cell membrane. Biochem Biophys Res Commun 415:619–626.  https://doi.org/10.1016/j.bbrc.2011.10.121CrossRefPubMedPubMedCentralGoogle Scholar
  11. Beekman M et al (2013) Genome-wide linkage analysis for human longevity: genetics of healthy aging study. Aging cell 12:184–193.  https://doi.org/10.1111/acel.12039CrossRefPubMedPubMedCentralGoogle Scholar
  12. Ben-Hur T, Ben-Menachem O, Furer V, Einstein O, Mizrachi-Kol R, Grigoriadis N (2003) Effects of proinflammatory cytokines on the growth, fate, and motility of multipotential neural precursor cells. Mol Cell Neurosci 24:623–631.  https://doi.org/10.1016/S1044-7431(03)00218-5 [pii]CrossRefPubMedGoogle Scholar
  13. Berdasco M, Esteller M (2012) Hot topics in epigenetic mechanisms of aging: 2011. Aging cell 11:181–186.  https://doi.org/10.1111/j.1474-9726.2012.00806.xCrossRefPubMedPubMedCentralGoogle Scholar
  14. Bobrie A, Colombo M, Raposo G, Thery C (2011) Exosome secretion: molecular mechanisms and roles in immune responses. Traffic 12:1659–1668.  https://doi.org/10.1111/j.1600-0854.2011.01225.xCrossRefPubMedGoogle Scholar
  15. Britschgi M et al (2011) Modeling of pathological traits in Alzheimer’s disease based on systemic extracellular signaling proteome. Mol Cell Proteomics 10: M111 008862.  https://doi.org/10.1074/mcp.m111.008862CrossRefGoogle Scholar
  16. Bruunsgaard H (2006) The clinical impact of systemic low-level inflammation in elderly populations. With special reference to cardiovascular disease, dementia and mortality. Dan Med Bull 53:285–309. doi: DMB3834 [pii]Google Scholar
  17. Burkle A et al (2015) MARK-AGE biomarkers of ageing. Mech Ageing Dev 151:2–12.  https://doi.org/10.1016/j.mad.2015.03.006CrossRefPubMedGoogle Scholar
  18. Cao P, Maximov A, Sudhof TC (2011) Activity-dependent IGF-1 exocytosis is controlled by the Ca(2+)-sensor synaptotagmin-10. Cell 145:300–311.  https://doi.org/10.1016/j.cell.2011.03.034PubMedPubMedCentralCrossRefGoogle Scholar
  19. Caruso C, Accardi G, Virruso C, Candore G (2013) Sex, gender and immunosenescence: a key to understand the different lifespan between men and women? Immun Ageing 10:20.  https://doi.org/10.1186/1742-4933-10-20
  20. Castellano JM et al (2017) Human umbilical cord plasma proteins revitalize hippocampal function in aged mice. Nature 544:488–492.  https://doi.org/10.1038/nature22067CrossRefPubMedPubMedCentralGoogle Scholar
  21. Chamoun V et al (2001) Haptoglobins as markers of blood-CSF barrier dysfunction: the findings in normal CSF. J Neurol Sci 182:117–121. doi: S0022-510X(00)00461-5 [pii]Google Scholar
  22. Chang H, Lau AL, Matzuk MM (2001) Studying TGF-beta superfamily signaling by knockouts and knockins. Mol Cell Endocrinol 180:39–46. doi: S0303-7207(01)00513-5 [pii]Google Scholar
  23. Chauhan SC et al (2006) Aberrant expression of MUC4 in ovarian carcinoma: diagnostic significance alone and in combination with MUC1 and MUC16 (CA125). Mod Pathol 19:1386–1394.  https://doi.org/10.1038/modpathol.3800646PubMedCrossRefGoogle Scholar
  24. Chen X et al (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997–1006.  https://doi.org/10.1038/cr.2008.282. cr2008282 [pii]PubMedCrossRefGoogle Scholar
  25. Childs BG, Durik M, Baker DJ, van Deursen JM (2015) Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat Med 21:1424–1435.  https://doi.org/10.1038/nm.4000CrossRefPubMedPubMedCentralGoogle Scholar
  26. Chilton W, O’Brien B, Charchar F (2017) Telomeres, Aging and Exercise: Guilty by Association? Int J Mol Sci 18.  https://doi.org/10.3390/ijms18122573PubMedCentralCrossRefPubMedGoogle Scholar
  27. Cipollone F et al (2011) A unique microRNA signature associated with plaque instability in humans. Stroke 42:2556–2563.  https://doi.org/10.1161/strokeaha.110.597575PubMedCrossRefGoogle Scholar
  28. Colombo M, Raposo G, Thery C (2014) Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 30:255–289.  https://doi.org/10.1146/annurev-cellbio-101512-122326CrossRefPubMedGoogle Scholar
  29. Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA (2005) Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433:760–764 doi: nature03260 [pii].  https://doi.org/10.1038/nature03260
  30. Crowe FL, Skeaff CM, Green TJ, Gray AR (2008) Serum n-3 long-chain PUFA differ by sex and age in a population-based survey of New Zealand adolescents and adults. Br J Nutr 99:168–174.  https://doi.org/10.1017/s000711450779387xCrossRefPubMedGoogle Scholar
  31. Cuccaro ML et al (2016) SORL1 mutations in early- and late-onset Alzheimer disease. Neurol Genet 2:e116.  https://doi.org/10.1212/nxg.0000000000000116PubMedPubMedCentralCrossRefGoogle Scholar
  32. Czesnikiewicz-Guzik M et al (2008) T cell subset-specific susceptibility to aging. Clin Immunol 127:107–118.  https://doi.org/10.1016/j.clim.2007.12.002PubMedCrossRefGoogle Scholar
  33. Daniali L et al (2013) Telomeres shorten at equivalent rates in somatic tissues of adults. Nat Commun 4:1597.  https://doi.org/10.1038/ncomms2602
  34. Dewailly E, Blanchet C, Gingras S, Lemieux S, Holub BJ (2002) Cardiovascular disease risk factors and n-3 fatty acid status in the adult population of James Bay Cree. Am J Clin Nutr 76:85–92.  https://doi.org/10.1093/ajcn/76.1.85PubMedCrossRefGoogle Scholar
  35. Dewailly E, Blanchet C, Lemieux S, Sauve L, Gingras S, Ayotte P, Holub BJ (2001) n-3 Fatty acids and cardiovascular disease risk factors among the Inuit of Nunavik. Am J Clin Nutr 74:464–473.  https://doi.org/10.1093/ajcn/74.4.464PubMedCrossRefGoogle Scholar
  36. Dharap A, Bowen K, Place R, Li LC, Vemuganti R (2009) Transient focal ischemia induces extensive temporal changes in rat cerebral microRNAome. J Cereb Blood Flow Metab Official J Int Soc Cereb Blood Flow Metab 29:675–687.  https://doi.org/10.1038/jcbfm.2008.157 jcbfm2008157 [pii]CrossRefGoogle Scholar
  37. Di Benedetto S, Derhovanessian E, Steinhagen-Thiessen E, Goldeck D, Muller L, Pawelec G (2015) Impact of age, sex and CMV-infection on peripheral T cell phenotypes: results from the Berlin BASE-II Study. Biogerontology 16:631–643.  https://doi.org/10.1007/s10522-015-9563-2PubMedCrossRefGoogle Scholar
  38. Ding J, Kopchick JJ (2011) Plasma biomarkers of mouse aging. Age (Dordr) 33:291–307.  https://doi.org/10.1007/s11357-010-9179-zPubMedPubMedCentralCrossRefGoogle Scholar
  39. Duncan ID, Brower A, Kondo Y, Curlee JF, Schultz RD (2009) Extensive remyelination of the CNS leads to functional recovery. Proc Natl Acad Sci U S A 106:6832–6836.  https://doi.org/10.1073/pnas.0812500106CrossRefGoogle Scholar
  40. Edgar JM, Nave KA (2009) The role of CNS glia in preserving axon function. Curr Opin Neurobiol 19:498–504.  https://doi.org/10.1016/j.conb.2009.08.003PubMedCrossRefGoogle Scholar
  41. Egerman MA et al (2015) GDF11 increases with age and inhibits skeletal muscle regeneration. Cell Metab 22:164–174.  https://doi.org/10.1016/j.cmet.2015.05.010. S1550-4131(15)00222-3 [pii]PubMedPubMedCentralCrossRefGoogle Scholar
  42. Ehrlenbach S et al (2009) Influences on the reduction of relative telomere length over 10 years in the population-based Bruneck Study: introduction of a well-controlled high-throughput assay. Int J Epidemiol 38:1725–1734.  https://doi.org/10.1093/ije/dyp273PubMedCrossRefGoogle Scholar
  43. Eitan E et al (2017) Age-related changes in plasma extracellular vesicle characteristics and internalization by Leukocytes. Sci Rep 7:1342.  https://doi.org/10.1038/s41598-017-01386-z
  44. Engelhardt B, Liebner S (2014) Novel insights into the development and maintenance of the blood-brain barrier. Cell Tissue Res 355:687–699.  https://doi.org/10.1007/s00441-014-1811-2PubMedPubMedCentralCrossRefGoogle Scholar
  45. Felsky D et al (2014) The SORL1 gene and convergent neural risk for Alzheimer’s disease across the human lifespan. Mol Psychiatry 19:1125–1132.  https://doi.org/10.1038/mp.2013.142PubMedPubMedCentralCrossRefGoogle Scholar
  46. Fichtlscherer S et al (2010) Circulating microRNAs in patients with coronary artery disease. Circ Res 107:677–684.  https://doi.org/10.1161/circresaha.109.215566. CIRCRESAHA.109.215566 [pii]PubMedCrossRefGoogle Scholar
  47. Fossel M (2000) Cell senescence in human aging: a review of the theory. In Vivo 14:29–34Google Scholar
  48. Fraga MF, Esteller M (2007) Epigenetics and aging: the targets and the marks. Trends Genet 23:413–418. doi: S0168-9525(07)00186-2 [pii].  https://doi.org/10.1016/j.tig.2007.05.008
  49. Franceschi C et al (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128:92–105.  https://doi.org/10.1016/j.mad.2006.11.016PubMedCrossRefGoogle Scholar
  50. Franco RS (2012) Measurement of red cell lifespan and aging. Transfus Med Hemother 39:302–307.  https://doi.org/10.1159/000342232PubMedPubMedCentralCrossRefGoogle Scholar
  51. Friedrich U, Griese E, Schwab M, Fritz P, Thon K, Klotz U (2000) Telomere length in different tissues of elderly patients. Mech Ageing Dev 119:89–99PubMedCrossRefGoogle Scholar
  52. Furuya TK et al (2012) SORL1 and SIRT1 mRNA expression and promoter methylation levels in aging and Alzheimer’s Disease. Neurochem Int 61:973–975.  https://doi.org/10.1016/j.neuint.2012.07.014PubMedCrossRefGoogle Scholar
  53. Gattinoni L et al. (2011) A human memory T cell subset with stem cell-like properties. Nature Med 17:1290–1297.  https://doi.org/10.1038/nm.2446PubMedPubMedCentralCrossRefGoogle Scholar
  54. Genot E, Petit-Koskas E, Sensenbrenner M, Labourdette G, Kolb JP (1989) Potentiation of the proliferative response of human B lymphocytes to low molecular weight B cell growth factor (LMW-BCGF) by fibroblast growth factors (FGFs). Cell Immunol 122:424–439PubMedCrossRefGoogle Scholar
  55. Gercel-Taylor C, Atay S, Tullis RH, Kesimer M, Taylor DD (2012) Nanoparticle analysis of circulating cell-derived vesicles in ovarian cancer patients. Anal Biochem 428:44–53.  https://doi.org/10.1016/j.ab.2012.06.004PubMedCrossRefGoogle Scholar
  56. Gilson J, Blakemore WF (1993) Failure of remyelination in areas of demyelination produced in the spinal cord of old rats. Neuropathol Appl Neurobiol 19:173–181PubMedCrossRefGoogle Scholar
  57. Goebeler S, Jylha M, Hervonen A (2003) Medical history, cognitive status and mobility at the age of 90. A population-based study in Tampere, Finland. Aging Clin Exp Res 15:154–161PubMedCrossRefGoogle Scholar
  58. Gramatges MM, Bertuch AA (2010) Measuring relative telomere length: is tissue an issue? Aging 2:756–757.  https://doi.org/10.18632/aging.100236PubMedPubMedCentralCrossRefGoogle Scholar
  59. Guo D et al (2013) Alteration in abundance and compartmentalization of inflammation-related miRNAs in plasma after intracerebral hemorrhage. Stroke; J Cereb Circ 44:1739–1742.  https://doi.org/10.1161/strokeaha.111.000835 STROKEAHA.111.000835 [pii]PubMedCrossRefGoogle Scholar
  60. Gustafson-Wagner EA et al (2007) Loss of mXinalpha, an intercalated disk protein, results in cardiac hypertrophy and cardiomyopathy with conduction defects. Am J Physiol Heart Circ Physiol 293:H2680–2692.  https://doi.org/10.1152/ajpheart.00806.2007PubMedPubMedCentralCrossRefGoogle Scholar
  61. Hannum G et al (2013) Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell 49:359–367.  https://doi.org/10.1016/j.molcel.2012.10.016PubMedPubMedCentralCrossRefGoogle Scholar
  62. Hansson LO, Kjellman NI, Ludvigsson J, Lundh B, Tibbling G (1983) Haptoglobin concentrations in children aged 9–10 years and its correlation to indirect parameters of erythrocyte turnover. Scand J Clin Lab Invest 43:367–370PubMedGoogle Scholar
  63. Hauri-Hohl M, Zuklys S, Hollander GA, Ziegler SF (2014) A regulatory role for TGF-beta signaling in the establishment and function of the thymic medulla. Nature Immunol 15:554–561.  https://doi.org/10.1038/ni.2869 ni.2869 [pii]PubMedCrossRefGoogle Scholar
  64. Heidinger BJ, Blount JD, Boner W, Griffiths K, Metcalfe NB, Monaghan P (2012) Telomere length in early life predicts lifespan. Proc Natl Acad Sci U S A 109:1743–1748.  https://doi.org/10.1073/pnas.1113306109CrossRefGoogle Scholar
  65. Holme I, Aastveit AH, Hammar N, Jungner I, Walldius G (2009) Haptoglobin and risk of myocardial infarction, stroke, and congestive heart failure in 342,125 men and women in the Apolipoprotein MOrtality RISk study (AMORIS). Ann Med 41:522–532.  https://doi.org/10.1080/07853890903089453PubMedCrossRefGoogle Scholar
  66. Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biol 14.  https://doi.org/10.1186/gb-2013-14-10-r115PubMedPubMedCentralCrossRefGoogle Scholar
  67. Horvath S, Raj K (2018) DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet 19:371–384.  https://doi.org/10.1038/s41576-018-0004-3CrossRefPubMedPubMedCentralGoogle Scholar
  68. Hosokawa Y, Hosokawa I, Ozaki K, Nakae H, Matsuo T (2006) Cytokines differentially regulate ICAM-1 and VCAM-1 expression on human gingival fibroblasts. Clin Exp Immunol 144:494–502 doi: CEI3064 [pii].  https://doi.org/10.1111/j.1365-2249.2006.03064.x
  69. Huang YC, Wu YR, Tseng MY, Chen YC, Hsieh SY, Chen CM (2011) Increased prothrombin, apolipoprotein A-IV, and haptoglobin in the cerebrospinal fluid of patients with Huntington’s disease. PloS one 6:e15809.  https://doi.org/10.1371/journal.pone.0015809PubMedPubMedCentralCrossRefGoogle Scholar
  70. Hunter MP et al (2008) Detection of microRNA expression in human peripheral blood microvesicles. PloS one 3:e3694.  https://doi.org/10.1371/journal.pone.0003694PubMedPubMedCentralGoogle Scholar
  71. Hunter P (2012) The inflammation theory of disease. The growing realization that chronic inflammation is crucial in many diseases opens new avenues for treatment. EMBO Rep 13:968–970.  https://doi.org/10.1038/embor.2012.142PubMedPubMedCentralCrossRefGoogle Scholar
  72. Inaba M, Maede Y (1988) Correlation between protein 4.1a/4.1b ratio and erythrocyte life span. Biochimica et Biophysica Acta 944:256–264CrossRefGoogle Scholar
  73. Janas AM, Sapon K, Janas T, Stowell MH, Janas T (2016) Exosomes and other extracellular vesicles in neural cells and neurodegenerative diseases. Biochimica et Biophysica Acta 1858:1139–1151.  https://doi.org/10.1016/j.bbamem.2016.02.011CrossRefGoogle Scholar
  74. Jeyaseelan K, Lim KY, Armugam A (2008) MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke; J Cereb Circ 39:959–966.  https://doi.org/10.1161/strokeaha.107.500736PubMedCrossRefGoogle Scholar
  75. Johnson G et al. (1992) Cerebrospinal fluid protein variations in common to Alzheimer’s disease and schizophrenia. Appl Theor Electrophor 3:47–53Google Scholar
  76. Johnston RK, Balasubramanian S, Kasiganesan H, Baicu CF, Zile MR, Kuppuswamy D (2009) Beta3 integrin-mediated ubiquitination activates survival signaling during myocardial hypertrophy. FASEB J:Official Publ Fed Am Soc Exp Biol 23:2759–2771.  https://doi.org/10.1096/fj.08-127480PubMedPubMedCentralCrossRefGoogle Scholar
  77. Jylhava J, Jylha M, Lehtimaki T, Hervonen A, Hurme M (2012) Circulating cell-free DNA is associated with mortality and inflammatory markers in nonagenarians: the Vitality 90+ study. Exp Gerontol 47:372–378.  https://doi.org/10.1016/j.exger.2012.02.011PubMedCrossRefGoogle Scholar
  78. Jylhava J, Kotipelto T, Raitala A, Jylha 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 132:20–26.  https://doi.org/10.1016/j.mad.2010.11.001PubMedCrossRefGoogle Scholar
  79. Kaestner L, Minetti G (2017) The potential of erythrocytes as cellular aging models. Cell Death Differ 24:1475–1477.  https://doi.org/10.1038/cdd.2017.100CrossRefGoogle Scholar
  80. Katsimpardi L et al (2014) Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science 344:630–634.  https://doi.org/10.1126/science.1251141CrossRefPubMedPubMedCentralGoogle Scholar
  81. Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G (1997) daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277:942–946PubMedCrossRefGoogle Scholar
  82. King HW, Michael MZ, Gleadle JM (2012) Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer 12:421.  https://doi.org/10.1186/1471-2407-12-421
  83. Kumar D, Rizvi SI (2014) Markers of oxidative stress in senescent erythrocytes obtained from young and old age rats. Rejuvenation Res 17:446–452.  https://doi.org/10.1089/rej.2014.1573PubMedPubMedCentralCrossRefGoogle Scholar
  84. Kumar P, Wadhwa R, Gupta R, Chandra P, Maurya PK (2018) Spectroscopic determination of intracellular quercetin uptake using erythrocyte model and its implications in human aging. 3 Biotech 8:498.  https://doi.org/10.1007/s13205-018-1524-4
  85. Kumari S, Devi Gt, Badana A, Dasari VR, Malla RR (2015) CD151-A striking marker for cancer therapy. Biomark Cancer 7:7–11. https://doi.org/10.4137/bic.s21847
  86. Langford MP, Redens TB, Harris NR, Lee S, Jain SK, Reddy S, McVie R (2007) Plasma levels of cell-free apoptotic DNA ladders and gamma-glutamyltranspeptidase (GGT) in diabetic children. Exp Biol Med (Maywood) 232:1160–1169.  https://doi.org/10.3181/0701-rm-13PubMedCrossRefGoogle Scholar
  87. Lara J et al (2015) A proposed panel of biomarkers of healthy ageing. BMC Med 13:222.  https://doi.org/10.1186/s12916-015-0470-9
  88. Lee SW et al (2013) Absence of CCL2 is sufficient to restore hippocampal neurogenesis following cranial irradiation Brain Behav Immun 30:33–44.  https://doi.org/10.1016/j.bbi.2012.09.010. S0889-1591(12)00437-0 [pii]PubMedCrossRefGoogle Scholar
  89. Letondor A et al (2014) Erythrocyte DHA level as a biomarker of DHA status in specific brain regions of n-3 long-chain PUFA-supplemented aged rats. Br J Nutr 112:1805–1818.  https://doi.org/10.1017/s0007114514002529PubMedCrossRefGoogle Scholar
  90. Levine ME et al (2018) An epigenetic biomarker of aging for lifespan and healthspan. Aging 10:573–591.  https://doi.org/10.18632/aging.101414PubMedPubMedCentralCrossRefGoogle Scholar
  91. Li T et al (2011) Identification of miR-130a, miR-27b and miR-210 as serum biomarkers for atherosclerosis obliterans. Clinica Chimica Acta; Int J Clin Chem 412:66–70.  https://doi.org/10.1016/j.cca.2010.09.029 S0009-8981(10)00595-4 [pii]CrossRefGoogle Scholar
  92. Liang Y, Ridzon D, Wong L, Chen C (2007) Characterization of microRNA expression profiles in normal human tissues. BMC Genomics 8:166.  https://doi.org/10.1186/1471-2164-8-166PubMedPubMedCentralCrossRefGoogle Scholar
  93. Lichtenwalner RJ, Forbes ME, Bennett SA, Lynch CD, Sonntag WE, Riddle DR (2001) Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience 107:603–613PubMedCrossRefGoogle Scholar
  94. Lin E, Tsai SJ, Kuo PH, Liu YL, Yang AC, Kao CF (2017) Association and interaction effects of Alzheimer’s disease-associated genes and lifestyle on cognitive aging in older adults in a Taiwanese population. Oncotarget 8:24077–24087.  https://doi.org/10.18632/oncotarget.15269
  95. Loffredo FS et al (2013) Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy Cell 153:828–839.  https://doi.org/10.1016/j.cell.2013.04.015 S0092-8674(13)00456-X [pii]PubMedPubMedCentralCrossRefGoogle Scholar
  96. Lotvall J et al (2014) Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J Extracell Vesicles 3:26913.  https://doi.org/10.3402/jev.v3.26913PubMedCrossRefGoogle Scholar
  97. Lu Y, Monaco G, Camous X, Andiappan AK, Rotzschke O, Ng TP, Larbi A (2018) Biomarker signatures predicting 10-year all-cause and disease-specific mortality. J Gerontol A Biol Sci Med Sci.  https://doi.org/10.1093/gerona/gly138CrossRefGoogle Scholar
  98. Marioni RE et al (2016) The epigenetic clock and telomere length are independently associated with chronological age and mortality. Int J Epidemiol.  https://doi.org/10.1093/ije/dyw041PubMedCentralCrossRefPubMedGoogle Scholar
  99. Marioni RE et al (2015) The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936. Int J Epidemiol 44:1388–1396.  https://doi.org/10.1093/ije/dyu277PubMedPubMedCentralCrossRefGoogle Scholar
  100. Marioni RE et al (2019) Tracking the epigenetic clock across the human life course: a meta-analysis of longitudinal cohort data. J Gerontol A Biol Sci Med Sci 74:57–61.  https://doi.org/10.1093/gerona/gly060CrossRefGoogle Scholar
  101. Mohanty BP et al (2016) DHA and EPA content and fatty acid profile of 39 food fishes from India. Biomed Res Int 2016:4027437.  https://doi.org/10.1155/2016/4027437CrossRefGoogle Scholar
  102. Monje ML, Toda H, Palmer TD (2003) Inflammatory blockade restores adult hippocampal neurogenesis. Science 302:1760–1765.  https://doi.org/10.1126/science.1088417PubMedCrossRefGoogle Scholar
  103. Morin SJ et al (2018) DNA methylation-based age prediction and telomere length in white blood cells and cumulus cells of infertile women with normal or poor response to ovarian stimulation. Aging.  https://doi.org/10.18632/aging.101670PubMedPubMedCentralCrossRefGoogle Scholar
  104. Mueller TJ, Jackson CW, Dockter ME, Morrison M (1987) Membrane skeletal alterations during in vivo mouse red cell aging. Increase in the band 4.1a:4.1b ratio. J Clin Investig 79:492–499.  https://doi.org/10.1172/jci112839PubMedPubMedCentralCrossRefGoogle Scholar
  105. Murphy T, Thuret S (2015) The systemic milieu as a mediator of dietary influence on stem cell function during ageing. Ageing Res Rev 19:53–64.  https://doi.org/10.1016/j.arr.2014.11.004 S1568-1637(14)00126-3 [pii]PubMedCrossRefGoogle Scholar
  106. Olivieri F, Rippo MR, Monsurro V, Salvioli S, Capri M, Procopio AD, Franceschi C (2013a) MicroRNAs linking inflamm-aging, cellular senescence and cancer. Ageing Res Rev 12:1056–1068.  https://doi.org/10.1016/j.arr.2013.05.001PubMedCrossRefGoogle Scholar
  107. Olivieri F, Rippo MR, Procopio AD, Fazioli F (2013b) Circulating inflamma-miRs in aging and age-related diseases. Front Genet 4:121.  https://doi.org/10.3389/fgene.2013.00121
  108. Ouyang W, Beckett O, Ma Q, Li MO (2010) Transforming growth factor-beta signaling curbs thymic negative selection promoting regulatory T cell development. Immunity 32:642–653.  https://doi.org/10.1016/j.immuni.2010.04.012 S1074-7613(10)00161-5 [pii]PubMedPubMedCentralCrossRefGoogle Scholar
  109. Pan M et al (2017) Aging systemic milieu impairs outcome after ischemic stroke in rats. Aging Dis 8:519–530.  https://doi.org/10.14336/ad.2017.0710CrossRefPubMedPubMedCentralGoogle Scholar
  110. Puca AA et al (2008) Fatty acid profile of erythrocyte membranes as possible biomarker of longevity. Rejuvenation Res 11:63–72.  https://doi.org/10.1089/rej.2007.0566CrossRefPubMedGoogle Scholar
  111. Pusic AD, Kraig RP (2014) Youth and environmental enrichment generate serum exosomes containing miR-219 that promote CNS myelination. Glia 62:284–299.  https://doi.org/10.1002/glia.22606PubMedPubMedCentralCrossRefGoogle Scholar
  112. Puszyk WM, Crea F, Old RW (2009) Unequal representation of different unique genomic DNA sequences in the cell-free plasma DNA of individual donors. Clin Biochem 42:736–738.  https://doi.org/10.1016/j.clinbiochem.2008.11.006PubMedCrossRefGoogle Scholar
  113. Ratanasopa K, Chakane S, Ilyas M, Nantasenamat C, Bulow L (2013) Trapping of human hemoglobin by haptoglobin: molecular mechanisms and clinical applications. Antioxid Redox Signal 18:2364–2374.  https://doi.org/10.1089/ars.2012.4878CrossRefGoogle Scholar
  114. Rebo J, Mehdipour M, Gathwala R, Causey K, Liu Y, Conboy MJ, Conboy IM (2016) A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood. Nat Commun 7:13363.  https://doi.org/10.1038/ncomms13363
  115. Reynolds CA et al (2013) Sortilin receptor 1 predicts longitudinal cognitive change. Neurobiol Aging 34:1710 e1711–1718.  https://doi.org/10.1016/j.neurobiolaging.2012.12.006CrossRefGoogle Scholar
  116. Rizvi SI, Jha R, Maurya PK (2006) Erythrocyte plasma membrane redox system in human aging. Rejuvenation Res 9:470–474.  https://doi.org/10.1089/rej.2006.9.470PubMedCrossRefGoogle Scholar
  117. Rizvi SI, Maurya PK (2008) L-cysteine influx in erythrocytes as a function of human age. Rejuvenation Res 11:661–665.  https://doi.org/10.1089/rej.2007.0652CrossRefPubMedGoogle Scholar
  118. Rizvi SI, Pandey KB (2010) Activation of the erythrocyte plasma membrane redox system by resveratrol: a possible mechanism for antioxidant properties. Pharmacol Rep 62:726–732PubMedCrossRefGoogle Scholar
  119. Rodriguez M et al (2014) Different exosome cargo from plasma/bronchoalveolar lavage in non-small-cell lung cancer. Genes Chromosom Cancer 53:713–724.  https://doi.org/10.1002/gcc.22181
  120. Rojanathammanee L, Rakoczy S, Kopchick J, Brown-Borg HM (2014) Effects of insulin-like growth factor 1 on glutathione S-transferases and thioredoxin in growth hormone receptor knockout mice. Age (Dordr) 36:9687.  https://doi.org/10.1007/s11357-014-9687-3
  121. Ruckh JM, Zhao JW, Shadrach JL, van Wijngaarden P, Rao TN, Wagers AJ, Franklin RJ (2012) Rejuvenation of regeneration in the aging central nervous system. Cell Stem Cell 10:96–103.  https://doi.org/10.1016/j.stem.2011.11.019 S1934-5909(11)00580-7 [pii]PubMedPubMedCentralCrossRefGoogle Scholar
  122. Sanders JL, Newman AB (2013) Telomere length in epidemiology: a biomarker of aging, age-related disease, both, or neither? Epidemiol Rev 35:112–131.  https://doi.org/10.1093/epirev/mxs008PubMedPubMedCentralCrossRefGoogle Scholar
  123. Santiago-Dieppa DR, Steinberg J, Gonda D, Cheung VJ, Carter BS, Chen CC (2014) Extracellular vesicles as a platform for ‘liquid biopsy’ in glioblastoma patients. Expert Rev Mol Diagn 14:819–825.  https://doi.org/10.1586/14737159.2014.943193PubMedPubMedCentralCrossRefGoogle Scholar
  124. Sebastiani P, Perls TT (2012) The genetics of extreme longevity: lessons from the new England centenarian study. Front Genet 3:277.  https://doi.org/10.3389/fgene.2012.00277
  125. Sebastiani P, Thyagarajan B, Sun F, Schupf N, Newman AB, Montano M, Perls TT (2017) Biomarker signatures of aging. Aging cell 16:329–338.  https://doi.org/10.1111/acel.12557PubMedPubMedCentralCrossRefGoogle Scholar
  126. Selvamani A, Williams MH, Miranda RC, Sohrabji F (2014) Circulating miRNA profiles provide a biomarker for severity of stroke outcomes associated with age and sex in a rat model. Clin Sci (Lond) 127:77–89.  https://doi.org/10.1042/cs20130565PubMedCrossRefGoogle Scholar
  127. Sheinerman KS, Umansky SR (2013) Circulating cell-free microRNA as biomarkers for screening, diagnosis and monitoring of neurodegenerative diseases and other neurologic pathologies. Frontiers Cell Neurosci 7:150.  https://doi.org/10.3389/fncel.2013.00150
  128. Silva-Vargas V, Maldonado-Soto AR, Mizrak D, Codega P, Doetsch F (2016) Age-dependent niche signals from the choroid plexus regulate adult neural stem cells. Cell Stem Cell 19:643–652. doi: S1934-5909(16)30163-1 [pii].  https://doi.org/10.1016/j.stem.2016.06.013
  129. Sim FJ, Zhao C, Penderis J, Franklin RJ (2002) The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. J Neurosci: Official J Soc Neurosci 22:2451–2459. doi:20026217Google Scholar
  130. Simons MJ (2015) Questioning causal involvement of telomeres in aging. Ageing Res Rev 24:191–196.  https://doi.org/10.1016/j.arr.2015.08.002PubMedCrossRefGoogle Scholar
  131. Sinha M et al (2014) Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle. Science 344:649–652.  https://doi.org/10.1126/science.1251152PubMedPubMedCentralCrossRefGoogle Scholar
  132. Smith JA, Leonardi T, Huang B, Iraci N, Vega B, Pluchino S (2015a) Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases. Biogerontology 16:147–185.  https://doi.org/10.1007/s10522-014-9510-7PubMedPubMedCentralCrossRefGoogle Scholar
  133. Smith LK et al (2015b) Beta2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis. Nat Med 21:932–937.  https://doi.org/10.1038/nm.3898PubMedPubMedCentralCrossRefGoogle Scholar
  134. Smith LK, White CW, Villeda SA (2018) The systemic environment: at the interface of aging and adult neurogenesis. Cell Tissue Res 371:105–113.  https://doi.org/10.1007/s00441-017-2715-8PubMedPubMedCentralCrossRefGoogle Scholar
  135. Sonntag WE, Deak F, Ashpole N, Toth P, Csiszar A, Freeman W, Ungvari Z (2013) Insulin-like growth factor-1 in CNS and cerebrovascular aging. Front Aging Neurosci 5:27.  https://doi.org/10.3389/fnagi.2013.00027
  136. Soo CY, Song Y, Zheng Y, Campbell EC, Riches AC, Gunn-Moore F, Powis SJ (2012) Nanoparticle tracking analysis monitors microvesicle and exosome secretion from immune cells. Immunology 136:192–197.  https://doi.org/10.1111/j.1365-2567.2012.03569.xPubMedPubMedCentralCrossRefGoogle Scholar
  137. Spagnuolo MS et al (2014) Haptoglobin increases with age in rat hippocampus and modulates Apolipoprotein E mediated cholesterol trafficking in neuroblastoma cell lines. Frontiers Cell Neurosci 8:212.  https://doi.org/10.3389/fncel.2014.00212
  138. Suzuki M, Jagger AL, Konya C, Shimojima Y, Pryshchep S, Goronzy JJ, Weyand CM (2012) CD8+CD45RA+CCR7+FOXP3+T cells with immunosuppressive properties: a novel subset of inducible human regulatory T cells. J Immunol 189:2118–2130.  https://doi.org/10.4049/jimmunol.1200122PubMedCrossRefGoogle Scholar
  139. Tan KS, Armugam A, Sepramaniam S, Lim KY, Setyowati KD, Wang CW, Jeyaseelan K (2009) Expression profile of MicroRNAs in young stroke patients. PloS one 4:e7689.  https://doi.org/10.1371/journal.pone.0007689PubMedPubMedCentralCrossRefGoogle Scholar
  140. Targowski T, Jahnz-Rozyk K, Plusa T, Glodzinska-Wyszogrodzka E (2005) Influence of age and gender on serum eotaxin concentration in healthy and allergic people. J Invest Allergol Clin Immunol 15:277–282Google Scholar
  141. Tatar M, Kopelman A, Epstein D, Tu MP, Yin CM, Garofalo RS (2001) A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 292:107–110.  https://doi.org/10.1126/science.1057987PubMedCrossRefGoogle Scholar
  142. Tedone E et al (2018) Telomere length and telomerase activity in T cells are biomarkers of high-performing centenarians. Aging Cell:e12859.  https://doi.org/10.1111/acel.12859PubMedPubMedCentralCrossRefGoogle Scholar
  143. Teo YV, Capri M, Morsiani C, Pizza G, Faria AMC, Franceschi C, Neretti N (2018) Cell-free DNA as a biomarker of aging. Aging Cell:e12890.  https://doi.org/10.1111/acel.12890PubMedPubMedCentralCrossRefGoogle Scholar
  144. Thompson MJ et al. (2018) A multi-tissue full lifespan epigenetic clock for mice. Aging 10:2832–2854.  https://doi.org/10.18632/aging.101590PubMedPubMedCentralCrossRefGoogle Scholar
  145. Tricola GM et al. (2018) The rate of telomere loss is related to maximum lifespan in birds. Philos Trans R Soc Lond B Biol Sci 373.  https://doi.org/10.1098/rstb.2016.0445CrossRefGoogle Scholar
  146. Tsang JC, Lo YM (2007) Circulating nucleic acids in plasma/serum. Pathology 39:197–207.  https://doi.org/10.1080/00313020701230831PubMedCrossRefGoogle Scholar
  147. Turpin D et al (2016) Role of extracellular vesicles in autoimmune diseases. Autoimmun Rev 15:174–183.  https://doi.org/10.1016/j.autrev.2015.11.004PubMedCrossRefGoogle Scholar
  148. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659.  https://doi.org/10.1038/ncb1596PubMedCrossRefGoogle Scholar
  149. Valiathan R, Ashman M, Asthana D (2016) Effects of ageing on the immune system: infants to elderly. Scand J Immunol 83:255–266.  https://doi.org/10.1111/sji.12413CrossRefPubMedGoogle Scholar
  150. Verschoor CP et al (2017) The relation between DNA methylation patterns and serum cytokine levels in community-dwelling adults: a preliminary study. BMC Genet 18:57.  https://doi.org/10.1186/s12863-017-0525-3
  151. Vicario-Abejon C, Yusta-Boyo MJ, Fernandez-Moreno C, de Pablo F (2003) Locally born olfactory bulb stem cells proliferate in response to insulin-related factors and require endogenous insulin-like growth factor-I for differentiation into neurons and glia. J Neurosci: Official J Soc Neurosci 23:895–906PubMedCrossRefGoogle Scholar
  152. Villeda SA et al (2011) The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature 477:90–94.  https://doi.org/10.1038/nature10357CrossRefPubMedPubMedCentralGoogle Scholar
  153. Villeda SA et al (2014) Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nature Med 20:659–663.  https://doi.org/10.1038/nm.3569PubMedPubMedCentralCrossRefGoogle Scholar
  154. von Zglinicki T, Martin-Ruiz CM (2005) Telomeres as biomarkers for ageing and age-related diseases. Curr Mol Med 5:197–203CrossRefGoogle Scholar
  155. Wagner KH, Cameron-Smith D, Wessner B, Franzke B (2016) Biomarkers of aging: from function to molecular biology. Nutrients 8.  https://doi.org/10.3390/nu8060338PubMedCentralCrossRefPubMedGoogle Scholar
  156. Wang K, Zhang S, Weber J, Baxter D, Galas DJ (2010) Export of microRNAs and microRNA-protective protein by mammalian cells. Nucleic Acids Res 38:7248–7259.  https://doi.org/10.1093/nar/gkq601PubMedPubMedCentralCrossRefGoogle Scholar
  157. Wyss-Coray T (2016) Ageing, neurodegeneration and brain rejuvenation. Nature 539:180–186.  https://doi.org/10.1038/nature20411PubMedPubMedCentralCrossRefGoogle Scholar
  158. Xia S et al (2016) An update on inflamm-aging: mechanisms, prevention, and treatment. J Immunol Res 2016:8426874.  https://doi.org/10.1155/2016/8426874CrossRefGoogle Scholar
  159. Xia X, Chen W, McDermott J, Han JJ (2017) Molecular and phenotypic biomarkers of aging. F1000Res 6:860.  https://doi.org/10.12688/f1000research.10692.1PubMedPubMedCentralCrossRefGoogle Scholar
  160. Xiong Y et al (2017) Vitamin C and E supplements enhance the antioxidant capacity of erythrocytes obtained from aged rats. Rejuvenation Res 20:85–92.  https://doi.org/10.1089/rej.2016.1835PubMedCrossRefGoogle Scholar
  161. Yanez-Mo M et al (2015) Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles 4:27066.  https://doi.org/10.3402/jev.v4.27066PubMedCrossRefGoogle Scholar
  162. Yin RH et al (2016) Impact of SORL1 genetic variations on MRI markers in non-demented elders. Oncotarget 7:31689–31698.  https://doi.org/10.18632/oncotarget.9300
  163. Yousef H et al (2015) Systemic attenuation of the TGF-beta pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal. Oncotarget 6:11959–11978.  https://doi.org/10.18632/oncotarget.3851CrossRefPubMedPubMedCentralGoogle Scholar
  164. Yousef H et al (2018) Aged blood inhibits hippocampal neurogenesis and activates microglia through VCAM1 at the blood-brain barrier. [PREPRINT] bioRxiv.  https://doi.org/10.1101/242198
  165. Zhang J, Alcaide P, Liu L, Sun J, He A, Luscinskas FW, Shi GP (2011) Regulation of endothelial cell adhesion molecule expression by mast cells, macrophages, and neutrophils. PloS one 6:e14525.  https://doi.org/10.1371/journal.pone.0014525PubMedPubMedCentralCrossRefGoogle Scholar
  166. Zhao S, Fung-Leung WP, Bittner A, Ngo K, Liu X (2014) Comparison of RNA-Seq and microarray in transcriptome profiling of activated T cells. PloS one 9:e78644.  https://doi.org/10.1371/journal.pone.0078644PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pharmacology and NeuroscienceUniversity of North Texas Health Science CenterFort WorthUSA
  2. 2.Department of NeurologyNational Neuroscience InstituteSingaporeSingapore
  3. 3.Department of Pharmacology and NeuroscienceUniversity of North Texas Health Science Center at Fort WorthTXUSA

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