Abstract
Although human life expectancy has increased significantly over the last two centuries, this has not been paralleled by a similar rise in healthy life expectancy. Thus, an important goal of anti-aging research has been to reduce the impact of age-associated diseases as a way of extending the human healthspan. This review will explore some of the potential avenues which have emerged from this research as the most promising strategies and drug targets for therapeutic interventions to promote healthy aging.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Christensen K, Doblhammer G, Rau R, Vaupel JW (2009) Ageing populations: the challenges ahead. Lancet 374(9696):1196–1208
Kontis V, Bennett JE, Mathers CD, Li G, Foreman K, Ezzati M (2017) Future life expectancy in 35 industrialised countries: projections with a Bayesian model ensemble. Lancet 389(10076):1323–1335
Boss GR, Seegmiller JE (1981) Age-related physiological changes and their clinical significance. West J Med 135(6):434–440
Rizvi S, Raza ST, Mahdi F (2014) Telomere length variations in aging and age-related diseases. Curr Aging Sci 7(3):161–167
Melov S (2016) Geroscience approaches to increase healthspan and slow aging. F1000Res 5. pii: F1000 Faculty Rev-785. https://doi.org/10.12688/f1000research.7583.1
Hansen M, Kennedy BK (2016) Does longer lifespan mean longer healthspan? Trends Cell Biol 26(8):565–568
Crimmins EM (2015) Lifespan and healthspan: past, present, and promise. Gerontologist 55(6):901–911
Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25:585–621
Campisi J (2013) Aging, cellular senescence, and cancer. Annu Rev Physiol 75:685–705
Wang C, Jurk D, Maddick M, Nelson G, Martin-Ruiz C, von Zglinicki T (2009) DNA damage response and cellular senescence in tissues of aging mice. Aging Cell 8(3):311–323
Leong I (2018) Sustained caloric restriction in health. Nat Rev Endocrinol 14:322. https://doi.org/10.1038/s41574-018-0008-2
Redman LM, Smith SR, Burton JH, Martin CK, Il’yasova D, Ravussin E (2018) Metabolic slowing and reduced oxidative damage with sustained caloric restriction support the rate of living and oxidative damage theories of aging. Cell Metab 27(4):805–815.e4
Mitchell SJ, Martin-Montalvo A, Mercken EM, Palacios HH, Ward TM, Abulwerdi G et al (2014) The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet. Cell Rep 6(5):836–843
Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K et al (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460(7253):392–395
Zinovkin RA, Zamyatnin AA (2018) Mitochondria-targeted drugs. Curr Mol Pharmacol. https://doi.org/10.2174/1874467212666181127151059. [Epub ahead of print]
Payne BA, Chinnery PF (2015) Mitochondrial dysfunction in aging: much progress but many unresolved questions. Biochim Biophys Acta 1847(11):1347–1353
Faitg J, Reynaud O, Leduc-Gaudet JP, Gouspillou G (2017) Skeletal muscle aging and mitochondrial dysfunction: an update. Med Sci (Paris) 33(11):955–962
Hoppel CL, Lesnefsky EJ, Chen Q, Tandler B (2017) Mitochondrial dysfunction in cardiovascular aging. Adv Exp Med Biol 982:451–464
Morita M, Ikeshima-Kataoka H, Kreft M, Vardjan N, Zorec R, Noda M (2019) Metabolic plasticity of astrocytes and aging of the brain. Int J Mol Sci 20(4). pii: E941. https://doi.org/10.3390/ijms20040941
Kim SH, Kim H (2018). Inhibitory effect of astaxanthin on oxidative stress-induced mitochondrial dysfunction-a mini-review. Nutrients 10(9). pii: E1137. https://doi.org/10.3390/nu10091137
Son HG, Altintas O, Kim EJE, Kwon S, Lee SV (2019) Age-dependent changes and biomarkers of aging in Caenorhabditis elegans. Aging Cell 18(2):e12853. https://doi.org/10.1111/acel.12853
Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366(6454):461–464
Kenyon CJ (2010) The genetics of ageing. Nature 464(7288):504–512
Lakowski B, Hekimi S (1998) The genetics of caloric restriction in Caenorhabditis elegans. Proc Natl Acad Sci U S A 95(22):13091–13096
Fierro-González JC, González-Barrios M, Miranda-Vizuete A, Swoboda P (2011) The thioredoxin TRX-1 regulates adult lifespan extension induced by dietary restriction in Caenorhabditis elegans. Biochem Biophys Res Commun 406(3):478–482
Hansen M, Hsu AL, Dillin A, Kenyon C (2005) New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS Genet 1(1):119–128
Honda Y, Honda S (2002) Life span extensions associated with upregulation of gene expression of antioxidant enzymes in Caenorhabditis elegans; studies of mutation in the AGE-1, PI3 kinase homologue and short-term exposure to hyperoxia. J Am Aging Assoc 24(1):21–25
Yanase S, Yasuda K, Ishii N (2002) Adaptive responses to oxidative damage in three mutants of Caenorhabditis elegans (age-1, mev-1 and daf-16) that affect life span. Mech Ageing Dev 123(12):1579–1587
Yanase S, Ishii N (2008) Hyperoxia exposure induced hormesis decreases mitochondrial superoxide radical levels via Ins/IGF-1 signaling pathway in a long-lived age-1 mutant of Caenorhabditis elegans. J Radiat Res 49(3):211–218
Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA et al (1997) The fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389(6654):994–999
Lin K, Dorman JB, Rodan A, Kenyon C (1997) daf-16: an HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 278(5341):1319–1322
Kenyon C (2006) Enrichment of regulatory motifs upstream of predicted DAF-16 targets. Nat Genet 38(4):397–398
Minniti AN, Cataldo R, Trigo C, Vasquez L, Mujica P, Leighton F et al (2009) Methionine sulfoxide reductase A expression is regulated by the DAF-16/FOXO pathway in Caenorhabditis elegans. Aging Cell 8(6):690–705
Vanfleteren JR (1993) Oxidative stress and ageing in Caenorhabditis elegans. Biochem J 292(Pt 2):605–608
Murakami S, Johnson TE (1996) A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics 143(3):1207–1218
Van Voorhies WA, Ward S (1999) Genetic and environmental conditions that increase longevity in Caenorhabditis elegans decrease metabolic rate. Proc Natl Acad Sci U S A 96(20):11399–11403
Barsyte D, Lovejoy DA, Lithgow GJ (2001) Longevity and heavy metal resistance in daf-2 and age-1 long-lived mutants of Caenorhabditis elegans. FASEB J 15(3):627–634
Shoyama T, Shimizu Y, Suda H (2009) Decline in oxygen consumption correlates with lifespan in long-lived and short-lived mutants of Caenorhabditis elegans. Exp Gerontol 44(12):784–791
Larsen PL (1993) Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc Natl Acad Sci U S A 90(19):8905–8909
Wood WB (1988) Introduction to C. elegans biology. In: Wood WB, The Community of C. elegans Researchers (eds) The nematode Caenorhabditis elegans. Cold Spring Harbor Laboratory Press, New York, pp 1–16. ISBN: 0-87969-433-5
Riddle DL (1988) The dauer larva. In: Wood WB, The Community of C. elegans Researchers (eds) The nematode Caenorhabditis elegans. Cold Spring Harbor Laboratory Press, New York, pp 393–412. ISBN: 0-87969-433-5
Wadsworth WG, Riddle DL (1989) Developmental regulation of energy metabolism in Caenorhabditis elegans. Dev Biol 132(1):167–173
Van Voorhies WA, Ward S (2000) Broad oxygen tolerance in the nematode Caenorhabditis elegans. J Biol Chem 203(Pt 16):2467–2478
Vanfleteren JR, De Vreese A (1996) Rate of aerobic metabolism and superoxide production rate potential in the nematode Caenorhabditis elegans. J Exp Zool 274(2):93–100
Klass MR, Johnson TE (1985) Caenorhabditis elegans. In: Lints FA (ed) Non-mammalian models for research on aging. Karger, Basel, pp 164–187. ISBN: 3805540191
Chow DK, Glenn CF, Johnston JL, Goldberg IG, Wolkow CA (2006) Sarcopenia in the Caenorhabditis elegans pharynx correlates with muscle contraction rate over lifespan. Exp Gerontol 41(3):252–260
Yanase S, Suda H, Yasuda K, Ishii N (2017) Impaired p53/CEP-1 is associated with lifespan extension through an age-related imbalance in the energy metabolism of C. elegans. Genes Cells 22(12):1004–1010
Owen OE, Kalhan SC, Hanson RW (2002) The key role of anaplerosis and cataplerosis for citric acid cycle function. J Biol Chem 277(34):30409–30412
Yang J, Kalhan SC, Hanson RW (2009) What is the metabolic role of phosphoenolpyruvate carboxykinase? J Biol Chem 284(40):27025–27029
Rodgers JT, Lerin C, Naas W, Gygi SP, Spiegelman BM, Puigserver P (2005) Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1. Nature 434(7029):113–118
Honda S, Matsuo M (1992) Lifespan shortening of the nematode Caenorhabditis elegans under higher concentrations of oxygen. Mech Ageing Dev 63(3):135–246
Darr D, Fridovich I (1995) Adaptation to oxidative stress in young, but not in mature or old, Caenorhabditis elegans. Free Radic Biol Med 18(2):195–201
Freeman BA, Crapo JD (1981) Hyperoxia increases oxygen radical production in rat lungs and lung mitochondria. J Biol Chem 256(21):10986–10992
Ishii N, Fujii M, Hartman PS, Tsuda M, Yasuda K, Senoo-Matsuda N et al (1998) A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature 394(6694):694–697
Senoo-Matsuda N, Yasuda K, Tsuda M, Ohkubo T, Yoshimura S, Nakazawa H et al (2001) A defect in the cytochrome b large subunit in complex II causes both superoxide anion overproduction and abnormal energy metabolism in Caenorhabditis elegans. J Biol Chem 276(45):41553–41558
DiMauro S, Schon EA (2003) Mitochondrial respiratory-chain diseases. N Engl J Med 348(26):2656–2568
Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11(3):298–300
Harman D (1972) The biologic clock: the mitochondria? J Am Geriatr Soc 20(4):145–147
Dai D-F, Chiao Y-A, Martin GM, Marcinek DJ, Basisty N, Quarles EK et al (2017) Mitochondrial-targeted catalase: extended longevity and the roles in various disease models. Prog Mol Biol Transl Sci 146:203–241
Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M et al (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308(5730):1909–1911
Li D, Lai Y, Yue Y, Rabinovitch PS, Hakim C, Duan D (2009) Ectopic catalase expression in mitochondria by adeno-associated virus enhances exercise performance in mice. In: Lucia A (ed). PLoS One 4:e6673. https://doi.org/10.1371/journal.pone.0006673
Selsby JT (2011) Increased catalase expression improves muscle function in mdx mice. Exp Physiol 96(2):194–202
Azadmanesh J, Borgstahl GEO (2018) A review of the catalytic mechanism of human manganese superoxide dismutase. Antioxidants (Basel, Switzerland) 7:25. https://doi.org/10.3390/antiox7020025
Zhou R-H, Vendrov AE, Tchivilev I, Niu X-L, Molnar KC, Rojas M et al (2012) Mitochondrial oxidative stress in aortic stiffening with age: the role of smooth muscle cell function. Arterioscler Thromb Vasc Biol 32(3):745–755
Salminen LE, Schofield PR, Pierce KD, Bruce SE, Griffin MG, Tate DF et al (2017) Vulnerability of white matter tracts and cognition to the SOD2 polymorphism: a preliminary study of antioxidant defense genes in brain aging. Behav Brain Res 329:111–119
Ernster L, Dallner G (1995) Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271(1):195–204
Hernández-Camacho JD, Bernier M, López-Lluch G, Navas P (2018) Coenzyme Q10 supplementation in aging and disease. Front Physiol 9:44. https://doi.org/10.3389/fphys.2018.00044
Shetty RA, Forster MJ, Sumien N (2013) Coenzyme Q(10) supplementation reverses age-related impairments in spatial learning and lowers protein oxidation. Age (Dordr) 35(5):1821–1834
Ulla A, Mohamed MK, Sikder B, Rahman AT, Sumi FA, Hossain M et al (2017) Coenzyme Q10 prevents oxidative stress and fibrosis in isoprenaline induced cardiac remodeling in aged rats. BMC Pharmacol Toxicol 18:29. https://doi.org/10.1186/s40360-017-0136-7
McManus MJ, Murphy MP, Franklin JL (2011) The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease. J Neurosci 31(44):15703–15715
Ng LF, Gruber J, Cheah IK, Goo CK, Cheong WF, Shui G et al (2014) The mitochondria-targeted antioxidant MitoQ extends lifespan and improves healthspan of a transgenic Caenorhabditis elegans model of Alzheimer disease. Free Radic Biol Med 71:390–401
Betz C, Hall MN (2013) Where is mTOR and what is it doing there? J Cell Biol 203(4):563–574
Fontana L, Partridge L, Longo VD (2010) Extending healthy life span--from yeast to humans. Science 328(5976):321–326
Kapahi P, Chen D, Rogers AN, Katewa SD, Li PW-L, Thomas EL et al (2010) With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab 11(6):453–465
Lamming DW, Ye L, Sabatini DM, Baur JA (2013) Rapalogs and mTOR inhibitors as anti-aging therapeutics. J Clin Invest 123(3):980–989
Xia Y, Sun M, Xie Y, Shu R (2017) mTOR inhibition rejuvenates the aging gingival fibroblasts through alleviating oxidative stress. Oxid Med Cell Longev 2017:6292630. https://doi.org/10.1155/2017/6292630
Araki T, Sasaki Y, Milbrandt J (2004) Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science 305(5686):1010–1013
Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B et al (2004) Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 305(5682):390–392
Nemoto S, Fergusson MM, Finkel T (2004) Nutrient availability regulates SIRT1 through a forkhead-dependent pathway. Science 306(5704):2105–2108
Bordone L, Motta MC, Picard F, Robinson A, Jhala US, Apfeld J et al (2006) Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells. In: Dillin A (ed). PLoS Biol 4:e31. https://doi.org/10.1371/journal.pbio.0040031
Gerhart-Hines Z, Rodgers JT, Bare O, Lerin C, Kim S-H, Mostoslavsky R et al (2007) Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J 26(7):1913–1923
Rodgers JT, Lerin C, Gerhart-Hines Z, Puigserver P (2008) Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways. FEBS Lett 582(1):46–53
Ramis MR, Esteban S, Miralles A, Tan D-X, Reiter RJ (2015) Caloric restriction, resveratrol and melatonin: role of SIRT1 and implications for aging and related-diseases. Mech Ageing Dev 146–148:28–41
Someya S, Yu W, Hallows WC, Xu J, Vann JM, Leeuwenburgh C et al (2010) Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell 143(5):802–812
Hebert AS, Dittenhafer-Reed KE, Yu W, Bailey DJ, Selen ES, Boersma MD et al (2013) Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome. Mol Cell 49(1):186–199
Pérez H, Finocchietto PV, Alippe Y, Rebagliati I, Elguero ME, Villalba N et al (2018) p66Shc inactivation modifies RNS production, regulates Sirt3 activity, and improves mitochondrial homeostasis, delaying the aging process in mouse brain. Oxid Med Cell Longev 2018:8561892. https://doi.org/10.1155/2018/8561892
Li Y, Ma Y, Song L, Yu L, Zhang L, Zhang Y et al (2018) SIRT3 deficiency exacerbates p53/Parkin-mediated mitophagy inhibition and promotes mitochondrial dysfunction: implication for aged hearts. Int J Mol Med 41(6):3517–3526
Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM et al (2006) Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325(5937):201–204
Colman RJ, Beasley TM, Kemnitz JW, Johnson SC, Weindruch R, Anderson RM (2014) Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun 5:3557. https://doi.org/10.1038/ncomms4557
Witte AV, Fobker M, Gellner R, Knecht S, Flöel A (2009) Caloric restriction improves memory in elderly humans. Proc Natl Acad Sci U S A 106(4):1255–1260
Aw TY (1991) Postnatal changes in pyridine nucleotides in rat hepatocytes: composition and O2 dependence. Pediatr Res 30(1):112–117
Ghosh D, Levault KR, Brewer GJ (2014) Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons. Aging Cell 13(4):631–640
Lenaz G, D’Aurelio M, Merlo Pich M, Genova ML, Ventura B, Bovina C et al (2000) Mitochondrial bioenergetics in aging. Biochim Biophys Acta 1459(2–3):397–404
Baciou L, Masoud R, Souabni H, Serfaty X, Karimi G, Bizouarn T et al (2018) Phagocyte NADPH oxidase, oxidative stress and lipids: anti- or pro ageing? Mech Ageing Dev 172:30–34
Sohal RS, Orr WC (2012) The redox stress hypothesis of aging. Free Radic Biol Med 52(3):539–555
Go YM, Jones DP (1979) Redox theory of aging: implications for health and disease. Clin Sci (Lond) 131(14):1669–1688
Barja G (2002) Rate of generation of oxidative stress-related damage and animal longevity. Free Radic Biol Med 33(9):1167–1172
Schindeldecker M, Stark M, Behl C, Moosmann B (2011) Differential cysteine depletion in respiratory chain complexes enables the distinction of longevity from aerobicity. Mech Ageing Dev 132(4):171–179
Paradies G, Paradies V, Ruggiero FM, Petrosillo G (2014) Cardiolipin and mitochondrial function in health and disease. Antioxid Redox Signal 20(12):1925–1953
Pollak N, Dölle C, Ziegler M (2007) The power to reduce: pyridine nucleotides--small molecules with a multitude of functions. Biochem J 402(2):205–218
Copes N, Edwards C, Chaput D, Saifee M, Barjuca I, Nelson D et al (2015) Metabolome and proteome changes with aging in Caenorhabditis elegans. Exp Gerontol 72:67–84
Mouchiroud L, Houtkooper RH, Moullan N, Katsyuba E, Ryu D, Cantó C et al (2013) The NAD(+)/Sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell 154(2):430–441
Gomes AP, Price NL, Ling AJ, Moslehi JJ, Montgomery MK, Rajman L et al (2013) Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 155(7):1624–1638
Ren X, Zou L, Zhang X, Branco V, Wang J, Carvalho C et al (2017) Redox signaling mediated by thioredoxin and glutathione systems in the central nervous system. Antioxid Redox Signal 27(13):989–1010
Veech RL, Bradshaw PC, Clarke K, Curtis W, Pawlosky R, King MT (2017) Ketone bodies mimic the life span extending properties of caloric restriction. IUBMB Life 69(5):305–314
Veech RL, Eggleston LV, Krebs HA (1969) The redox state of free nicotinamide-adenine dinucleotide phosphate in the cytoplasm of rat liver. Biochem J 115(4):609–619
Tischler ME, Friedrichs D, Coll K, Williamson JR (1977) Pyridine nucleotide distributions and enzyme mass action ratios in hepatocytes from fed and starved rats. Arch Biochem Biophys 184(1):222–236
Hanson GT, Aggeler R, Oglesbee D, Cannon M, Capaldi RA, Tsien RY et al (2004) Investigating mitochondrial redox potential with redox-sensitive green fluorescent protein indicators. J Biol Chem 279(13):13044–13053
Bradshaw PC (2019) Cytoplasmic and mitochondrial NADPH-coupled redox systems in the regulation of aging. Nutrients 11(3). pii: E504. https://doi.org/10.3390/nu11030504
Inoue K, Zhuang L, Ganapathy V (2002) Human Na+ -coupled citrate transporter: primary structure, genomic organization, and transport function. Biochem Biophys Res Commun 299(3):465–471
Rogina B, Reenan RA, Nilsen SP, Helfand SL (2000) Extended life-span conferred by cotransporter gene mutations in Drosophila. Science 290(5499):2137–2140
Anderson RM, Weindruch R (2012) The caloric restriction paradigm: implications for healthy human aging. Am J Hum Biol 24(2):101–106
Birkenfeld AL, Lee HY, Guebre-Egziabher F, Alves TC, Jurczak MJ, Jornayvaz FR et al (2011) Deletion of the mammalian INDY homolog mimics aspects of dietary restriction and protects against adiposity and insulin resistance in mice. Cell Metab 14(2):184–195
Gregolin C, Ryder E, Kleinschmidt AK, Warner RC, Lane MD (1966) Molecular characteristics of liver acetyl CoA carboxylase. Proc Natl Acad Sci U S A 56(1):148–155
Fu JY, Kemp RG (1973) Activation of muscle fructose 1,6-diphosphatase by creatine phosphate and citrate. J Biol Chem 248(3):1124–1125
Nielsen TT (1983) Plasma citrate in relation to glucose and free fatty acid metabolism in man. Dan Med Bull 30(6):357–378
Ros S, Schulze A (2013) Balancing glycolytic flux: the role of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatases in cancer metabolism. Cancer Metab 1(1):8. https://doi.org/10.1186/2049-3002-1-8
Huard K, Brown J, Jones JC, Cabral S, Futatsugi K, Gorgoglione M et al (2015) Discovery and characterization of novel inhibitors of the sodium-coupled citrate transporter (NaCT or SLC13A5). Sci Rep 5:17391. https://doi.org/10.1038/srep17391
Wang PY, Neretti N, Whitaker R, Hosier S, Chang C, Lu D et al (2009) Long-lived Indy and calorie restriction interact to extend life span. Proc Natl Acad Sci U S A 106(23):9262–9267
Pijpe J, Pul N, van Duijn S, Brakefield PM, Zwaan BJ (2011) Changed gene expression for candidate ageing genes in long-lived Bicyclus anynana butterflies. Exp Gerontol 46(6):426–434
Martinez-Beamonte R, Navarro MA, Guillen N, Acin S, Arnal C, Guzman MA et al (2011) Postprandial transcriptome associated with virgin olive oil intake in rat liver. Front Biosci (Elite Ed) 3:11–21
Etcheverry A, Aubry M, de Tayrac M, Vauleon E, Boniface R, Guenot F et al (2010) DNA methylation in glioblastoma: impact on gene expression and clinical outcome. BMC Genomics 11:701. https://doi.org/10.1186/1471-2164-11-701
Tian Y, Arai E, Gotoh M, Komiyama M, Fujimoto H, Kanai Y (2014) Prognostication of patients with clear cell renal cell carcinomas based on quantification of DNA methylation levels of CpG island methylator phenotype marker genes. BMC Cancer 14:772. https://doi.org/10.1186/1471-2407-14-772
DÃaz M, GarcÃa C, Sebastiani G, de Zegher F, López-Bermejo A, Ibáñez L (2016) Placental and cord blood methylation of genes involved in energy homeostasis: association with fetal growth and neonatal body composition. Diabetes 66(3):779–784. https://doi.org/10.2337/db16-0776
Neretti N, Wang PY, Brodsky AS, Nyguyen HH, White KP, Rogina B et al (2009) Long-lived Indy induces reduced mitochondrial reactive oxygen species production and oxidative damage. Proc Natl Acad Sci U S A 106(7):2277–2282
Neuschäfer-Rube F, Lieske S, Kuna M, Henkel J, Perry RJ, Erion DM, Pesta D et al (2014) The mammalian INDY homolog is induced by CREB in a rat model of type 2 diabetes. Diabetes 63(3):1048–1057
von Loeffelholz C, Döcke S, Lock JF, Lieske S, Horn P, Kriebel J et al (2017) Increased lipogenesis in spite of upregulated hepatic 5’AMP-activated protein kinase in human non-alcoholic fatty liver. Hepatol Res 47(9):890–901
Willmes DM, Helfand SL, Birkenfeld AL (2016) The longevity transporter mIndy (Slc13a5) as a target for treating hepatic steatosis and insulin resistance. Aging (Albany NY) 8(2):208–209
Willmes DM, Kurzbach A, Henke C, Schumann T, Zahn G, Heifetz A et al (2018) The longevity gene INDY (I’m Not Dead Yet) in metabolic control: potential as pharmacological target. Pharmacol Ther 185:1–11
Brachs S, Winkel AF, Tang H, Birkenfeld AL, Brunner B, Jahn-Hofmann K et al (2016) Inhibition of citrate cotransporter Slc13a5/mINDY by RNAi improves hepatic insulin sensitivity and prevents diet-induced non-alcoholic fatty liver disease in mice. Mol Metab 5(11):1072–1082
Guest PC (ed) (2019) Reviews on biomarker studies of metabolic and metabolism-related disorders. In: Advances in experimental medicine and biology, 1st edn. Springer, Cham. ISBN-10: 3030126676
Flegal KM, Kit BK, Orpana H, Graubard BI (2013) Association of all-cause mortality with overweight and obesity using standard body mass index categories a systematic review and meta-analysis. JAMA 309(1):71–82
Aune D, Sen A, Prasad M, Norat T, Janszky I, Tonstad S et al (2016) BMI and all cause mortality: systematic review and non-linear dose-response meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants. BMJ 353:i2156. https://doi.org/10.1136/bmj.i2156
Di Angelantonio E, Bhupathiraju SN, Wormser D, Gao P, Kaptoge S, de Gonzalez AB et al (2016) Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet 388(10046):776–786
Hubert HB, Feinleib M, McNamara PM, Castelli WP (1983) Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 67(5):968–977
Sacco MR, de Castro NP, Euclydes VLV, Souza JM, Rondó PH (2013) Birth weight, rapid weight gain in infancy and markers of overweight and obesity in childhood. Eur J Clin Nutr 67(11):1147–1153
Heitmann BL, Lissner L (1995) Dietary underreporting by obese individuals--is it specific or non-specific? BMJ 311(7011):986–989
Hariri N, Thibault L (2010) High-fat diet-induced obesity in animal models. Nutr Res Rev 23(2):270–299
Ong TP, Guest PC (2018) Nutritional programming effects on development of metabolic disorders in later life. Methods Mol Biol 1735:3–17
Mickelsen O, Takahashi S, Craig C (1955) Experimental obesity. J Nutr 57:541–554
Buettner R, Schölmerich J, Bollheimer LC (2007) High-fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity (Silver Spring) 15(4):798–808
Woods SC, D’Alessio DA, Tso P, Rushing PA, Clegg DJ, Benoit SC et al (2004) Consumption of a high-fat diet alters the homeostatic regulation of energy balance. Physiol Behav 83(4):573–578
Fontelles CC, Guido LN, Rosim MP et al (2016) Paternal programming of breast cancer risk in daughters in a rat model: opposing effects of animal- and plant-based high-fat diets. Breast Cancer Res 18:71. https://doi.org/10.1186/s13058-016-0729-x
Hariri N, Gougeon R, Thibault L (2010) A highly saturated fat-rich diet is more obesogenic than diets with lower saturated fat content. Nutr Res 30(9):632–643
Febbraio M, Podrez EA, Smith JD, Hajjar DP, Hazen SL, Hoff HF et al (2000) Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J Clin Invest 105(8):1049–1056
Pinheiro-Castro N, Silva LBAR, Novaes GM, Ong TP (2019) Hypercaloric diet-induced obesity and obesity-related metabolic disorders in experimental models. Adv Exp Med Biol 1134:149–161
Berridge KC, Ho C-Y, Richard JM, DiFeliceantonio AG (2010) The tempted brain eats: pleasure and desire circuits in obesity and eating disorders. Brain Res 1350:43–64
Castro L, Gao X, Moore AB, Yu L, Di X, Kissling GE et al (2016) A high concentration of genistein induces cell death in human uterine leiomyoma cells by autophagy. Expert Opin Environ Biol 5(Suppl 1). https://doi.org/10.4172/2325-9655.S1-003
Sampey BP, Vanhoose AM, Winfield HM, Freemerman AJ, Muehlbauer MJ, Fueger PT et al (2011) Cafeteria diet is a robust model of human metabolic syndrome with liver and adipose inflammation: comparison to high-fat diet. Obesity 19(6):1109–1117
Zeeni N, Dagher-Hamalian C, Dimassi H, Faour WH (2015) Cafeteria diet-fed mice is a pertinent model of obesity-induced organ damage: a potential role of inflammation. Inflamm Res 64(7):501–512
Maioli TU, Gonçalves JL, Miranda MCG, Martins VD, Horta LS, Moreira TG et al (2016) High sugar and butter (HSB) diet induces obesity and metabolic syndrome with decrease in regulatory T cells in adipose tissue of mice. Inflamm Res 65(2):169–178
Crescenzo R, Bianco F, Mazzoli A, Giacco A, Cancelliere R, di Fabio GA et al (2015) Fat quality influences the obesogenic effect of high fat diets. Nutrients 7(11):9475–9491
Aller EEJG, Abete I, Astrup A, Martinez JA, van Baak MA (2011) Starches, sugars and obesity. Nutrients 3(3):341–369
Lennerz B, Lennerz JK (2018) Food addiction, high-glycemic-index carbohydrates, and obesity. Clin Chem 64(1):64–71
Panchal SK, Poudyal H, Iyer A, Nazer R, Alam MA, Diwan V et al (2011) High-carbohydrate, high-fat diet–induced metabolic syndrome and cardiovascular remodeling in rats. J Cardiovasc Pharmacol 57(5):611–624
Hung WW, Ross JS, Boockvar KS, Siu AL (2011) Recent trends in chronic disease, impairment and disability among older adults in the United States. BMC Geriatr 11:47. https://doi.org/10.1186/1471-2318-11-47
Madreiter-Sokolowski CT, Sokolowski AA, Waldeck-Weiermair M, Malli R, Graier WF (2018) Targeting mitochondria to counteract age-related cellular dysfunction. Genes (Basel) 9(3):pii: E165. https://doi.org/10.3390/genes9030165
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Guest, P.C. (2019). Metabolic Biomarkers in Aging and Anti-Aging Research. 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_13
Download citation
DOI: https://doi.org/10.1007/978-3-030-25650-0_13
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-25649-4
Online ISBN: 978-3-030-25650-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)