Skip to main content
SpringerLink
Log in
Book cover

Reviews on Biomarker Studies in Aging and Anti-Aging Research pp 39–56Cite as

Aging Biomarkers and Novel Targets for Anti-Aging Interventions

Part of the Advances in Experimental Medicine and Biology book series (PMISB,volume 1178)

Abstract

The aging population worldwide is expanding at an increasing rate. By 2050, approximately a quarter of the world population will consist of the elderly. To slow down the aging process, exploration of aging biomarkers and the search for novel antiaging targets have attracted much interest. Nonetheless, because aging research is costly and time-consuming and the aging process is complicated, aging research is considered one of the most difficult biological fields. Here, providing a broader definition of aging biomarkers, we review cutting-edge research on aging biomarkers at the molecular, cellular, and organismal levels, thus shedding light on the relations between aging and telomeres, longevity proteins, a senescence-associated secretory phenotype, the gut microbiota and metabolic patterns. Furthermore, we evaluate the suitability of these aging biomarkers for the development of novel antiaging targets on the basis of the most recent research on this topic. We also discuss the possible implications and some controversies regarding these biomarkers for therapeutic interventions in aging and age-related disease processes. We have attempted to cover all of the latest research on aging biomarkers in our review but there are countless studies on aging biomarkers, and the topic of aging interventions will continue to deepen even further. We hope that our review can serve as a reference for better characterization of aging and as inspiration for the screening of antiaging drugs as well as give some clues to further research into aging biomarkers and antiaging targets.

Keywords

  • Aging biomarker
  • Telomere
  • Longevity protein
  • Senescence-associated secretory phenotype
  • Gut microbiota
  • Metabolism

This is a preview of subscription content, access via your institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   129.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   179.99
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

Learn about institutional subscriptions

References

  1. United Nations DoEaS, Population Division (2017) World population prospects: the 2017 revision, key findings and advance tables. https://esa.un.org/unpd/wpp/Publications/Files/WPP2017_KeyFindings.pdf

  2. Vijg J, Campisi J (2008) Puzzles, promises and a cure for ageing. Nature 454(7208):1065–1071

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  3. Jones OR, Scheuerlein A, Salguero-Gomez R, Camarda CG, Schaible R, Casper BB et al (2014) Diversity of ageing across the tree of life. Nature 505(7482):169–173

    CrossRef  CAS  PubMed  Google Scholar 

  4. Tian X, Azpurua J, Hine C, Vaidya A, Myakishev-Rempel M, Ablaeva J et al (2013) High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature 499(7458):346–349

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lowsky DJ, Olshansky SJ, Bhattacharya J, Goldman DP (2014) Heterogeneity in healthy aging. J Gerontol A Biol Sci Med Sci 69(6):640–649

    CrossRef  PubMed  Google Scholar 

  6. Patrick JB, Melanie MW, Chen C, Morgan EL, Kristine Y, Steven PR, Bret RR (2018) Biological Age, Not Chronological Age, Is Associated with Late-Life Depression. The Journals of Gerontology: Series A 73(10):1370–1376

    Google Scholar 

  7. Kim S-J, Kim BJ, Kang H (2017) Measurement of biological age may help to assess the risk of colorectal adenoma in screening colonoscopy. World J Gastroenterol 23(37):6877–6883

    CrossRef  PubMed  PubMed Central  Google Scholar 

  8. Zhang W, Jia L, Cai G, Shao F, Lin H, Liu Z et al (2017) Model construction for biological age based on a cross-sectional study of a healthy Chinese han population. J Nutr Health Aging 21(10):1233–1239

    CrossRef  CAS  PubMed  Google Scholar 

  9. Borkan GA, Norris AH (1980) Biological age in adulthood: comparison of active and inactive U.S. males. Hum Biol 52(4):787–802

    CAS  PubMed  Google Scholar 

  10. Bernardes de Jesus B, Blasco MA (2012) Potential of telomerase activation in extending health span and longevity. Curr Opin Cell Biol 24(6):739–743

    CrossRef  CAS  PubMed  Google Scholar 

  11. Janssens GE, Lin X-X, Millan-Arino L, Kavsek A, Sen I, Seinstra RI et al (2019) Transcriptomics-based screening identifies pharmacological inhibition of Hsp90 as a means to defer aging. Cell Rep 27(2):467–480.e6

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  12. Blackburn EH (1990) Telomeres: structure and synthesis. J Biol Chem 265(11):5919–5921

    CAS  PubMed  Google Scholar 

  13. Blackburn EH (2005) Telomeres and telomerase: their mechanisms of action and the effects of altering their functions. FEBS Lett 579(4):859–862

    CrossRef  CAS  PubMed  Google Scholar 

  14. Honig LS, Kang MS, Cheng R, Eckfeldt JH, Thyagarajan B, Leiendecker-Foster C et al (2015) Heritability of telomere length in a study of long-lived families. Neurobiol Aging 36(10):2785–2790

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  15. Strong MA, Vidal-Cardenas SL, Karim B, Yu H, Guo N, Greider CW (2011) Phenotypes in mTERT(+/−) and mTERT(−/−) mice are due to short telomeres, not telomere-independent functions of telomerase reverse transcriptase. Mol Cell Biol 31(12):2369–2379

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jaskelioff M, Muller FL, Paik J-H, Thomas E, Jiang S, Adams AC et al (2011) Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 469(7328):102–106

    CrossRef  CAS  PubMed  Google Scholar 

  17. Wang Q, Zhan Y, Pedersen NL, Fang F, Hagg S (2018) Telomere length and all-cause mortality: a meta-analysis. Ageing Res Rev 48:11–20

    CrossRef  CAS  PubMed  Google Scholar 

  18. Simoncini T, Hafezl-Moghadam A, Brazil DP, Ley K, Chin WW, Liao JK (2000) Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature 407(6803):538–541

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  19. Austad SN (2006) Why women live longer than men: sex differences in longevity. Gend Med 3(2):79–92

    CrossRef  PubMed  Google Scholar 

  20. Sansoni P, Cossarizza A, Brianti V, Fagnoni F, Snelli G, Monti D et al (1993) Lymphocyte subsets and natural killer cell activity in healthy old people and centenarians. Blood 82(9):2767–2773

    CAS  PubMed  Google Scholar 

  21. Fulop T, Larbi A, Dupuis G, Le Page A, Frost EH, Cohen AA et al (2017) Immunosenescence and inflamm-aging as two sides of the same coin: friends or foes? Front Immunol 8:1960. https://doi.org/10.3389/fimmu.2017.01960

    CrossRef  CAS  PubMed  Google Scholar 

  22. D’Mello MJ, Ross SA, Briel M, Anand SS, Gerstein H, Pare G (2015) Association between shortened leukocyte telomere length and cardiometabolic outcomes: systematic review and meta-analysis. Circ Cardiovasc Genet 8(1):82–90

    CrossRef  CAS  PubMed  Google Scholar 

  23. Panossian LA, Porter VR, Valenzuela HF, Zhu X, Reback E, Masterman D et al (2003) Telomere shortening in T cells correlates with Alzheimer’s disease status. Neurobiol Aging 24(1):77–84

    CrossRef  CAS  PubMed  Google Scholar 

  24. Dai D-F, Chiao YA, Marcinek DJ, Szeto HH, Rabinovitch PS (2014) Mitochondrial oxidative stress in aging and healthspan. Longev Healthspan 3:6. https://doi.org/10.1186/2046-2395-3-6

    CrossRef  PubMed  PubMed Central  Google Scholar 

  25. Serra V, von Zglinicki T, Lorenz M, Saretzki G (2003) Extracellular superoxide dismutase is a major antioxidant in human fibroblasts and slows telomere shortening. J Biol Chem 278(9):6824–6830

    CrossRef  CAS  PubMed  Google Scholar 

  26. Liu L, Trimarchi JR, Smith PJS, Keefe DL (2002) Mitochondrial dysfunction leads to telomere attrition and genomic instability. Aging Cell 1(1):40–46

    CrossRef  CAS  PubMed  Google Scholar 

  27. Latifovic L, Peacock SD, Massey TE, King WD (2016) The influence of alcohol consumption, cigarette smoking, and physical activity on leukocyte telomere length. Cancer Epidemiol Biomark Prev 25(2):374–380

    CrossRef  CAS  Google Scholar 

  28. Shay JW (2016) Role of telomeres and telomerase in aging and cancer. Cancer Disgov 6(6):584–593

    CrossRef  CAS  Google Scholar 

  29. Savage SA, Gadalla SM, Chanock SJ (2013) The long and short of telomeres and cancer association studies. J Natl Cancer Inst 105(7):448–449

    CrossRef  PubMed  PubMed Central  Google Scholar 

  30. Mensà E, Latini S, Ramini D, Storci G, Bonafè M, Olivieri F (2019) The telomere world and aging: analytical challenges and future perspectives. Ageing Res Rev 50:27–42

    CrossRef  CAS  PubMed  Google Scholar 

  31. Ames BN (2018) Prolonging healthy aging: longevity vitamins and proteins. Proc Natl Acad Sci U S A 115(43):10836–10844

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  32. Sinclair DA, Guarente L (1997) Extrachromosomal rDNA circles—a cause of aging in yeast. Cell 91(7):1033–1042

    CrossRef  CAS  PubMed  Google Scholar 

  33. Guarente L (2000) Sir2 links chromatin silencing, metabolism, and aging. Genes Dev 14(9):1021–1026

    CAS  PubMed  Google Scholar 

  34. Fang Y, Tang S, Li X (2019) Sirtuins in metabolic and epigenetic regulation of stem cells. Trends Endocrinol Metab 30(3):177–188

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  35. Watroba M, Szukiewicz D (2016) The role of sirtuins in aging and age-related diseases. Adv Med Sci 61(1):52–62

    CrossRef  PubMed  Google Scholar 

  36. Wątroba M, Dudek I, Skoda M, Stangret A, Rzodkiewicz P, Szukiewicz D (2017) Sirtuins, epigenetics and longevity. Ageing Res Rev 40:11–19

    CrossRef  CAS  PubMed  Google Scholar 

  37. Kanfi Y, Shalman R, Peshti V, Pilosof SN, Gozlan YM, Pearson KJ et al (2008) Regulation of SIRT6 protein levels by nutrient availability. FEBS Lett 582(5):543–548

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  38. Alcendor RR, Gao S, Zhai P, Zablocki D, Holle E, Yu X et al (2007) Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res 100(10):1512–1521

    CrossRef  CAS  PubMed  Google Scholar 

  39. Tasselli L, Zheng W, Chua KF (2017) SIRT6: novel mechanisms and links to aging and disease. Trends Endocrinol Metab 28(3):168–185

    CrossRef  CAS  PubMed  Google Scholar 

  40. Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, Gellon L et al (2006) Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124(2):315–329

    CrossRef  CAS  PubMed  Google Scholar 

  41. Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G, Nahum L et al (2012) The sirtuin SIRT6 regulates lifespan in male mice. Nature 483(7388):218–221

    CrossRef  CAS  PubMed  Google Scholar 

  42. Xiao N-M, Zhang Y-M, Zheng Q, Gu J (2004) Klotho is a serum factor related to human aging. Chin Med J 117(5):742–747

    CAS  PubMed  Google Scholar 

  43. Laszczyk AM, Fox-Quick S, Vo HT, Nettles D, Pugh PC, Overstreet-Wadiche L, King GD (2017) Klotho regulates postnatal neurogenesis and protects against age-related spatial memory loss. Neurobiol Aging 59:41–54

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  44. Benoit B, Meugnier E, Castelli M, Chanon S, Vieille-Marchiset A, Durand C, Bendridi N, Pesenti S, Monternier PA, Durieux AC, Freyssenet D, Rieusset J, Lefai E, Vidal H, Ruzzin J (2017) Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice. Nat Med 23:990–996

    CrossRef  CAS  PubMed  Google Scholar 

  45. Sahu A, Mamiya H, Shinde SN, Cheikhi A, Winter LL, Vo NV et al (2018) Age-related declines in alpha-Klotho drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration. Nat Commun 9(1):4859. https://doi.org/10.1038/s41467-018-07253-3

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kenyon C (2005) The plasticity of aging: insights from long-lived mutants. Cell 120(4):449–460

    CrossRef  CAS  PubMed  Google Scholar 

  47. Lee W-S, Kim J (2018) Insulin-like growth factor-1 signaling in cardiac aging. Biochim Biophys Acta Mol Basis Dis 1864(5 Pt B):1931–1938

    CrossRef  CAS  PubMed  Google Scholar 

  48. Tullet JM, Hertweck M, An JH, Baker J, Hwang JY, Liu S et al (2008) Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell 132(6):1025–1038

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  49. Bartke A (2008) Impact of reduced insulin-like growth factor-1/insulin signaling on aging in mammals: novel findings. Aging Cell 7(3):285–290

    CrossRef  CAS  PubMed  Google Scholar 

  50. Ben-Avraham D, Govindaraju DR, Budagov T, Fradin D, Durda P, Liu B et al (2017) The GH receptor exon 3 deletion is a marker of male-specific exceptional longevity associated with increased GH sensitivity and taller stature. Sci Adv 3(6):e1602025. https://doi.org/10.1126/sciadv.1602025

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  51. Suh Y, Atzmon G, Cho M-O, Hwang D, Liu B, Leahy DJ et al (2008) Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci U S A 105(9):3438–3442

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kennedy BK, Lamming DW (2016) The mechanistic target of rapamycin: the grand conducTOR of metabolism and aging. Cell Metab 23(6):990–1003

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  53. Shimobayashi M, Hall MN (2014) Making new contacts: the mTOR network in metabolism and signalling crosstalk. Nat Rev Mol Cell Biol 15(3):155–162

    CrossRef  CAS  PubMed  Google Scholar 

  54. Arriola Apelo SI, Neuman JC, Baar EL, Syed FA, Cummings NE, Brar HK, Pumper CP, Kimple ME, Lamming DW (2016) Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system. Aging Cell 15:28–38

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  55. Coppé J-P, Patil CK, Rodier F, Sun Y, Muñoz DP, Goldstein J et al (2008) Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 6(12):2853–2868. https://doi.org/10.1371/journal.pbio.0060301

    CrossRef  CAS  PubMed  Google Scholar 

  56. Campisi J (2011) Cellular senescence: putting the paradoxes in perspective. Curr Opin Genet Dev 21(1):107–112

    CrossRef  CAS  PubMed  Google Scholar 

  57. Schafer MJ, White TA, Iijima K, Haak AJ, Ligresti G, Atkinson EJ et al (2017) Cellular senescence mediates fibrotic pulmonary disease. Nat Commun 8:14532. https://doi.org/10.1038/ncomms14532

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  58. Rodier F, Coppé J-P, Patil CK, Hoeijmakers WA, Muñoz DP, Raza SR et al (2009) Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat Cell Biol 11(8):973–979

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  59. Shelton DN, Chang E, Whittier PS, Choi D, Funk WD (1999) Microarray analysis of replicative senescence. Curr Biol 9(17):939–945

    CrossRef  CAS  PubMed  Google Scholar 

  60. Kang C, Xu Q, Martin TD, Li MZ, Demaria M, Aron L et al (2015) The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science 349(6255):aaa5612. https://doi.org/10.1126/science.aaa5612

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  61. Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton JP et al (2013) A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol 15(8):978–990

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  62. Orjalo AV, Bhaumik D, Gengler BK, Scott GK, Campisi J (2009) Cell surface-bound IL-1α is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network. Proc Natl Acad Sci U S A 106(40):17031–17036

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  63. Mariotti M, Castiglioni S, Bernardini D, Maier JA (2006) Interleukin 1 alpha is a marker of endothelial cellular senescent. Immun Ageing 3:4. https://doi.org/10.1186/1742-4933-3-4

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  64. Freund A, Patil CK, Campisi J (2011) p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype. EMBO J 30(8):1536–1548

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  65. Laberge R-M, Sun Y, Orjalo AV, Patil CK, Freund A, Zhou L et al (2015) MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat Cell Biol 17(8):1049–1061

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  66. Meyer SC, Levine RL (2014) Molecular pathways: molecular basis for sensitivity and resistance to JAK kinase inhibitors. Clin Cancer Res 20(8):2051–2059

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  67. Liu S, Uppal H, Demaria M, Desprez P-Y, Campisi J, Kapahi P (2015) Simvastatin suppresses breast cancer cell proliferation induced by senescent cells. Sci Rep 5:17895. https://doi.org/10.1038/srep17895

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kirkland JL, Tchkonia T (2017) Cellular senescence: a translational perspective. EBioMedicine 21:21–28

    CrossRef  PubMed  PubMed Central  Google Scholar 

  69. Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM et al (2012) Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science 335(6076):1638–1643

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  70. Lehmann BD, Paine MS, Brooks AM, McCubrey JA, Renegar RH, Wang R et al (2008) Senescence-associated exosome release from human prostate cancer cells. Cancer Res 68(19):7864–7871

    CrossRef  CAS  PubMed  Google Scholar 

  71. Wang AL, Lukas TJ, Yuan M, Du N, Tso MO, Neufeld AH (2009) Autophagy and exosomes in the aged retinal pigment epithelium: possible relevance to drusen formation and age-related macular degeneration. PLoS One 4(1):e4160. https://doi.org/10.1371/journal.pone.0004160

    CrossRef  PubMed  PubMed Central  Google Scholar 

  72. Takasugi M, Okada R, Takahashi A, Chen DV, Watanabe S, Hara E (2017) Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2. Nat Commun 8:15729. https://doi.org/10.1038/ncomms15728

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  73. Mitsuhashi M, Taub DD, Kapogiannis D, Eitan E, Zukley L, Mattson MP et al (2013) Aging enhances release of exosomal cytokine mRNAs by Aβ1-42-stimulated macrophages. FASEB J 27(12):5141–5150

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  74. van Balkom BW, De Jong OG, Smits M, Brummelman J, den Ouden K, de Bree PM et al (2013) Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells. Blood 121(19):3997–4006

    CrossRef  CAS  PubMed  Google Scholar 

  75. Gan W, Liu XL, Yu T, Zou YG, Li TT, Wang S et al (2018) Urinary 8-oxo-7,8-dihydroguanosine as a potential biomarker of aging. Front Aging Neurosci 10:34. https://doi.org/10.3389/fnagi.2018.00034

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  76. Rodier F (2013) Detection of the senescence-associated secretory phenotype (SASP). Methods Mol Biol 965:165–173

    CrossRef  CAS  PubMed  Google Scholar 

  77. Thomas V, Clark J, Doré J (2015) Fecal microbiota analysis: an overview of sample collection methods and sequencing strategies. Future Microbiol 10(9):1485–1504

    CrossRef  CAS  PubMed  Google Scholar 

  78. Schneiderhan J, Master-Hunter T, Locke A (2016) Targeting gut flora to treat and prevent disease. J Fam Pract 65(1):34–38

    PubMed  Google Scholar 

  79. Rodriguez-Castaño GP, Caro-Quintero A, Reyes A, Lizcano F (2017) Advances in gut microbiome research, opening new strategies to cope with a western lifestyle. Front Genet 7:224. https://doi.org/10.3389/fgene.2016.00224

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  80. Vaiserman AM, Koliada AK, Marotta F (2017) Gut microbiota: a player in aging and a target for anti-aging intervention. Ageing Res Rev 35:36–45

    CrossRef  CAS  PubMed  Google Scholar 

  81. Guigoz Y, Doré J, Schiffrin EJ (2008) The inflammatory status of old age can be nurtured from the intestinal environment. Curr Opin Clin Nutr Metab Care 11(1):13–20

    CrossRef  PubMed  Google Scholar 

  82. Hopkins M, Sharp R, Macfarlane G (2002) Variation in human intestinal microbiota with age. Dig Liver Dis 34 Suppl 2:S12–S18

    CrossRef  CAS  PubMed  Google Scholar 

  83. Rondanelli M, Giacosa A, Faliva MA, Perna S, Allieri F, Castellazzi AM (2015) Review on microbiota and effectiveness of probiotics use in older. World J Clin Cases 3(2):156–162

    CrossRef  PubMed  PubMed Central  Google Scholar 

  84. Kato K, Odamaki T, Mitsuyama E, Sugahara H, J-z X, Osawa R (2017) Age-related changes in the composition of gut Bifidobacterium species. Cur Microbiol 74(8):987–995

    CrossRef  CAS  Google Scholar 

  85. O’Hagan C, Li JV, Marchesi JR, Plummer S, Garaiova I, Good MA (2017) Long-term multi-species Lactobacillus and Bifidobacterium dietary supplement enhances memory and changes regional brain metabolites in middle-aged rats. Neurobiol Learn Mem 144:36–47

    CrossRef  CAS  PubMed  Google Scholar 

  86. Gao J, Xu K, Liu H, Liu G, Bai M, Peng C et al (2018) Impact of the gut microbiota on intestinal immunity mediated by tryptophan metabolism. Front Cell Infect Microbiol 8:13. https://doi.org/10.3389/fcimb.2018.00013

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  87. Collino S, Montoliu I, Martin F-PJ, Scherer M, Mari D, Salvioli S et al (2013) Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism. PLoS One 8(3):e56564. https://doi.org/10.1371/journal.pone.0056564

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  88. Mace J, Porter R, Dalrymple-Alford J, Wesnes K, Anderson T (2010) Effects of acute tryptophan depletion on neuropsychological and motor function in Parkinson’s disease. J Psychopharmacol 24(10):1465–1472

    CrossRef  CAS  PubMed  Google Scholar 

  89. Roberts SB, Rosenberg I (2006) Nutrition and aging: changes in the regulation of energy metabolism with aging. Physiol Rev 86(2):651–667

    CrossRef  CAS  PubMed  Google Scholar 

  90. Verdin E (2015) NAD+ in aging, metabolism, and neurodegeneration. Science 350(6265):1208–1213

    CrossRef  CAS  PubMed  Google Scholar 

  91. Mendelsohn AR, Larrick JW (2017) The NAD+/PARP1/SIRT1 axis in aging. Rejuvenation Res 20(3):244–247

    CrossRef  CAS  PubMed  Google Scholar 

  92. Zhang H, Ryu D, Wu Y, Gariani K, Wang X, Luan P et al (2016) NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 352(6292):1436–1443

    CrossRef  CAS  PubMed  Google Scholar 

  93. Igarashi M, Miura M, Williams E, Jaksch F, Kadowaki T, Yamauchi T et al (2019) NAD+ supplementation rejuvenates aged gut adult stem cells. Aging Cell 18:e12935. https://doi.org/10.1111/acel.12935

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  94. Nacarelli T, Lau L, Fukumoto T, Zundell J, Fatkhutdinov N, Wu S et al (2019) NAD+ metabolism governs the proinflammatory senescence-associated secretome. Nat Cell Biol 21(3):397–407

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  95. Balasubramanian P, Howell PR, Anderson RM (2017) Aging and caloric restriction research: a biological perspective with translational potential. EBioMedicine 21:37–44

    CrossRef  PubMed  PubMed Central  Google Scholar 

  96. Meidenbauer JJ, Ta N, Seyfried TN (2014) Influence of a ketogenic diet, fish-oil, and calorie restriction on plasma metabolites and lipids in C57BL/6J mice. Nutr Metab (Lond) 11:23. https://doi.org/10.1186/1743-7075-11-23

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  97. Roberts MN, Wallace MA, Tomilov AA, Zhou Z, Marcotte GR, Tran D et al (2017) A ketogenic diet extends longevity and healthspan in adult mice. Cell Metab 26(3):539–546.e5

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  98. Newman JC, Verdin E (2017) β-Hydroxybutyrate: a signaling metabolite. Annu Rev Nutr 37:51–76

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  99. Scheibye-Knudsen M, Mitchell SJ, Fang EF, Iyama T, Ward T, Wang J et al (2014) A high-fat diet and NAD+ activate Sirt1 to rescue premature aging in cockayne syndrome. Cell Metab 20(5):840–855

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  100. Weber DD, Aminazdeh-Gohari S, Kofler B (2018) Ketogenic diet in cancer therapy. Aging (Albany NY) 10(2):164–165

    CrossRef  Google Scholar 

  101. Pyo J-O, Yoo S-M, Ahn H-H, Nah J, Hong S-H, Kam T-I et al (2013) Overexpression of Atg5 in mice activates autophagy and extends lifespan. Nat Commun 4:2300. https://doi.org/10.1038/ncomms3300

    CrossRef  CAS  PubMed  Google Scholar 

  102. Zhang C, Cuervo AM (2008) Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nat Med 14(9):959–965

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  103. Jiao J, Demontis F (2017) Skeletal muscle autophagy and its role in sarcopenia and organismal aging. Curr Opin Pharmacol 34:1–6

    CrossRef  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was financially supported by grants from the National Key R&D Program of China (2018YFC2000304 and 2018YFD0400204), National Natural Science Foundation of China (81871095), and the Key International S&T Cooperation Program of China (2016YFE113700).

Author information

Authors and Affiliations

  1. Protein Science Key Laboratory of the Ministry of Education, School of Pharmaceutical Sciences, Tsinghua University, Beijing, People’s Republic of China

    Kang Xu, Yannan Guo, Zhongchi Li & Zhao Wang

Authors
  1. Kang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yannan Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhongchi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhao Wang .

Editor information

Editors and Affiliations

  1. Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil

    Dr. Paul C. Guest

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

Xu, K., Guo, Y., Li, Z., Wang, Z. (2019). Aging Biomarkers and Novel Targets for Anti-Aging Interventions. In: Guest, P. (eds) Reviews on Biomarker Studies in Aging and Anti-Aging Research. Advances in Experimental Medicine and Biology(), vol 1178. Springer, Cham. https://doi.org/10.1007/978-3-030-25650-0_3

Download citation

Search

Navigation