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Current Metabolomics and Systems Biology (Discontinued)


ISSN (Print): 2666-3384
ISSN (Online): 2666-3392

Review Article

Cell Culture Studies: A Promising Approach to the Metabolomic Study of Human Aging

Author(s): Ana Rocha, Sandra Magalhães and Alexandra Nunes*

Volume 8, Issue 1, 2021

Published on: 22 March, 2021

Page: [1 - 26] Pages: 26

DOI: 10.2174/2666338408666210322113713

Price: $65


With the increasing aging of the world’s population, a detailed study of the characteristics of aging, and the pathologies related to this process, are crucial to the development of targeted anti-aging therapies. Therefore, there are several study models for the study of aging, from computational models to animals or even to cell cultures. The latter have shown high potential for aging studies as they are easier to handle, cheaper, do not require the same level of ethical consideration required for animal and human studies, and present little biological heterogeneity when grown under the same conditions and in the same context population. For aging studies, these characteristics are a great advantage since cells have a considerable variety of morphologic characteristics and markers that can be studied. Thus, the aim of this review is to offer an overview of the models used in studies of aging, with a focus on cell culture models, presenting the advantages and disadvantages of cell culture in the study of aging, of what information can we extract of these studies and how cell studies can be compared with the other models.

Keywords: Cell culture, aging, in vitro models of aging, cellular models of aging, anti-aging therapies, aging studies.

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Mc Auley MT, Guimera AM, Hodgson D, et al. Modelling the molecular mechanisms of aging. Biosci Rep 2017; 37(1): BSR20160177.
[] [PMID: 28096317]
Ludovico P, Osiewacz HD, Costa V, Burhans WC. Cellular models of aging. Oxid Med Cell Longev 2012; 2012: 616128.
[] [PMID: 23320129]
Mitchell SJ, Scheibye-Knudsen M, Longo DL, de Cabo R. Animal models of aging research: implications for human aging and age-related diseases. Annu Rev Anim Biosci 2015; 3: 283-303.
[] [PMID: 25689319]
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 2013; 153(6): 1194-217.
[] [PMID: 23746838]
Folgueras AR, Freitas-Rodríguez S, Velasco G, López-Otín C. Mouse models to disentangle the hallmarks of human aging. Circ Res 2018; 123(7): 905-24.
[] [PMID: 30355076]
Hoeijmakers JHJ. DNA damage, aging, and cancer. N Engl J Med 2009; 361(15): 1475-85.
[] [PMID: 19812404]
Worman HJ. Nuclear lamins and laminopathies. J Pathol 2012; 226(2): 316-25.
[] [PMID: 21953297]
Moskalev AA, Shaposhnikov MV, Plyusnina EN, et al. The role of DNA damage and repair in aging through the prism of Koch-like criteria. Ageing Res Rev 2013; 12(2): 661-84.
[] [PMID: 22353384]
Lord CJ, Ashworth A. The DNA damage response and cancer therapy. Nature 2012; 481(7381): 287-94.
[] [PMID: 22258607]
Kazak L, Reyes A, Holt IJ. Minimizing the damage: repair pathways keep mitochondrial DNA intact. Nat Rev Mol Cell Biol 2012; 13(10): 659-71.
[] [PMID: 22992591]
Blackburn EH, Greider CW, Szostak JW. Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging. Nat Med 2006; 12(10): 1133-8.
[] [PMID: 17024208]
Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet 2008; 42(1): 301-34.
[] [PMID: 18680434]
Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res 1961; 25: 585-621.
[] [PMID: 13905658]
Olovnikov AM. Telomeres, telomerase, and aging: origin of the theory. Exp Gerontol 1996; 31(4): 443-8.
[] [PMID: 9415101]
Fumagalli M, Rossiello F, Clerici M, et al. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat Cell Biol 2012; 14(4): 355-65.
[] [PMID: 22426077]
Han S, Brunet A. Histone methylation makes its mark on longevity. Trends Cell Biol 2012; 22(1): 42-9.
[] [PMID: 22177962]
Booth LN, Brunet A. The aging epigenome. Mol Cell 2016; 62(5): 728-44.
[] [PMID: 27259204]
van Ham TJ, Holmberg MA, van der Goot AT, et al. Identification of MOAG-4/SERF as a regulator of age-related proteotoxicity. Cell 2010; 142(4): 601-12.
[] [PMID: 20723760]
Magalhaes S, Goodfellow BJ, Nunes A. Aging and proteins: What does proteostasis have to do with age? Curr Mol Med 2018; 18(3): 178-89.
[] [PMID: 30198430]
Freitas-Rodríguez S, Folgueras AR, López-Otín C. The role of matrix metalloproteinases in aging: Tissue remodeling and beyond. Biochim Biophys Acta Mol Cell Res 2017; 1864(11, Part A): 2015-25.
[] [PMID: 28499917]
Koga H, Kaushik S, Cuervo AM. Protein homeostasis and aging: The importance of exquisite quality control. Ageing Res Rev 2011; 10(2): 205-15.
[] [PMID: 20152936]
Barzilai N, Huffman DM, Muzumdar RH, Bartke A. The critical role of metabolic pathways in aging. Diabetes 2012; 61(6): 1315-22.
[] [PMID: 22618766]
Sun N, Youle RJ, Finkel T. The mitochondrial basis of aging. Mol Cell 2016; 61(5): 654-66.
[] [PMID: 26942670]
Zhang H, Ryu D, Wu Y, et al. NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 2016; 352(6292): 1436-43.
[] [PMID: 27127236]
Hiona A, Sanz A, Kujoth GC, Pamplona R, Seo AY, Hofer T. Mitochondrial DNA mutations induce mitochondrial dysfunction, apoptosis and sarcopenia in skeletal muscle of mitochondrial DNA mutator mice. PLoS One 2010; 5(7): e11468-.
Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev 2007; 87(1): 99-163.
[] [PMID: 17237344]
Green DR, Galluzzi L, Kroemer G. Mitochondria and the autophagy-inflammation-cell death axis in organismal aging. Science 2011; 333(6046): 1109-12.
[] [PMID: 21868666]
Raffaello A, Rizzuto R. Mitochondrial longevity pathways. Biochimica et Biophysica Acta [BBA] -. Mol Cell Res 2011; 1813(1): 260-8.
Wiley CD, Velarde MC, Lecot P, et al. Mitochondrial dysfunction induces senescence with a distinct secretory phenotype. Cell Metab 2016; 23(2): 303-14.
[] [PMID: 26686024]
Kuilman T, Michaloglou C, Mooi WJ, Peeper DS. The essence of senescence. Genes Dev 2010; 24(22): 2463-79.
[] [PMID: 21078816]
Muñoz-Espín D, Serrano M. Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol 2014; 15(7): 482-96.
[] [PMID: 24954210]
Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol 2013; 75: 685-705.
[] [PMID: 23140366]
Rossi DJ, Bryder D, Seita J, Nussenzweig A, Hoeijmakers J, Weissman IL. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature 2007; 447(7145): 725-9.
[] [PMID: 17554309]
Janzen V, Forkert R, Fleming HE, et al. Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 2006; 443(7110): 421-6.
[] [PMID: 16957735]
Molofsky AV, Slutsky SG, Joseph NM, et al. Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 2006; 443(7110): 448-52.
[] [PMID: 16957738]
Gruber R, Koch H, Doll BA, Tegtmeier F, Einhorn TA, Hollinger JO. Fracture healing in the elderly patient. Exp Gerontol 2006; 41(11): 1080-93.
[] [PMID: 17092679]
Conboy IM, Rando TA. Heterochronic parabiosis for the study of the effects of aging on stem cells and their niches. Cell Cycle 2012; 11(12): 2260-7.
[] [PMID: 22617385]
Flores I, Blasco MA. The role of telomeres and telomerase in stem cell aging. FEBS Lett 2010; 584(17): 3826-30.
[] [PMID: 20674573]
Russell SJ, Kahn CR. Endocrine regulation of ageing. Nat Rev Mol Cell Biol 2007; 8(9): 681-91.
[] [PMID: 17684529]
Zhang G, Li J, Purkayastha S, et al. Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. Nature 2013; 497(7448): 211-6.
[] [PMID: 23636330]
Shefferson RP, Jones OR, Salguero-Gómez R, Eds. The evolution of senescence in the tree of life. Cambridge: Cambridge University Press 2017.
Campisi J. From cells to organisms: can we learn about aging from cells in culture? Exp Gerontol 2001; 36(4-6): 607-18.
[] [PMID: 11295503]
Carrel A. On the permanent life of tissues outside of the organism. J Exp Med 1912; 15(5): 516-28.
[] [PMID: 19867545]
Lidzbarsky G, Gutman D, Shekhidem HA, Sharvit L, Atzmon G. Genomic instabilities, cellular senescence, and aging: in vitro, in vivo and aging-like human syndromes. Front Med (Lausanne) 2018; 5: 104.
[] [PMID: 29719834]
Chernet B, Levin M. Endogenous voltage potentials and the microenvironment: bioelectric signals that reveal, induce and normalize cancer. J Clin Exp Oncol 2013; (Suppl. 1)S1-S002.
[PMID: 25525610]
Hooper ML, Subak-Sharpe JH. Metabolic cooperation between cells. International Review of Cytology. Academic Press 1981; pp. 45-104.
Potten CS, Loeffler M. Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development 1990; 110(4): 1001-20.
[PMID: 2100251]
de Pomerai DI, Kotecha B, Flor-Henry M, Fullick C, Young A, Gali MAH. Expression of differentiation markers by chick embryo neuroretinal cells in vivo and in culture. J Embryol Exp Morphol 1983; 77(1): 201-20.
[PMID: 6140294]
Chen H, Li Y, Tollefsbol TO. Cell senescence culturing methods. Methods Mol Biol 2013; 1048: 1-10.
[] [PMID: 23929093]
Cristofalo VJ, Pignolo RJ. Replicative senescence of human fibroblast-like cells in culture. Physiol Rev 1993; 73(3): 617-38.
[] [PMID: 8332640]
Cristofalo VJ, Lorenzini A, Allen RG, Torres C, Tresini M. Replicative senescence: a critical review. Mech Ageing Dev 2004; 125(10-11): 827-48.
[] [PMID: 15541776]
Cristofalo VJ. Cellular biomarkers of aging. Exp Gerontol 1988; 23(4-5): 297-307.
[] [PMID: 3197781]
Zhang R, Poustovoitov MV, Ye X, et al. Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev Cell 2005; 8(1): 19-30.
[] [PMID: 15621527]
Young ARJ, Narita M. SASP reflects senescence. EMBO Rep 2009; 10(3): 228-30.
[] [PMID: 19218920]
Ferber A, Chang C, Sell C, et al. Failure of senescent human fibroblasts to express the insulin-like growth factor-1 gene. J Biol Chem 1993; 268(24): 17883-8.
[] [PMID: 7688732]
Carlin C, Phillips PD, Brooks-Frederich K, Knowles BB, Cristofalo VJ. Cleavage of the epidermal growth factor receptor by a membrane-bound leupeptin-sensitive protease active in nonionic detergent lysates of senescent but not young human diploid fibroblasts. J Cell Physiol 1994; 160(3): 427-34.
[] [PMID: 8077280]
Seshadri T, Campisi J. Repression of c-fos transcription and an altered genetic program in senescent human fibroblasts. Science 1990; 247(4939): 205-9.
[] [PMID: 2104680]
Fedarko NS. The biology of aging and frailty. Clin Geriatr Med 2011; 27(1): 27-37.
[] [PMID: 21093720]
Mc Auley MT, Mooney KM. Computational systems biology for aging research. Interdiscip Top Gerontol 2015; 40: 35-48.
[] [PMID: 25341511]
Troen BR. The biology of aging. Mt Sinai J Med 2003; 70(1): 3-22.
[PMID: 12516005]
Auley M, Corfe B, Cuskelly G, Mooney K. Nutrition research and the impact of computational systems biology. J Comput Sci Syst Biol 2013; 6: 271.
Qi Q, Wattis JAD, Byrne HM. Stochastic simulations of normal aging and Werner’s syndrome. Bull Math Biol 2014; 76(6): 1241-69.
[] [PMID: 24771273]
Hirt BV, Wattis JAD, Preston SP. Modelling the regulation of telomere length: the effects of telomerase and G-quadruplex stabilising drugs. J Math Biol 2014; 68(6): 1521-52.
[] [PMID: 23620229]
Proctor CJ, Kirkwood TBL. Modelling cellular senescence as a result of telomere state. Aging Cell 2003; 2(3): 151-7.
[] [PMID: 12882407]
Portugal RD, Land MGP, Svaiter BF. A computational model for telomere-dependent cell-replicative aging. Biosystems 2008; 91(1): 262-7.
[] [PMID: 18063293]
Kowald A, Kirkwood TBL. Towards a network theory of ageing: a model combining the free radical theory and the protein error theory. J Theor Biol 1994; 168(1): 75-94.
[] [PMID: 8022192]
Kowald A, Jendrach M, Pohl S, Bereiter-Hahn J, Hammerstein P. On the relevance of mitochondrial fusions for the accumulation of mitochondrial deletion mutants: a modelling study. Aging Cell 2005; 4(5): 273-83.
[] [PMID: 16164426]
Tam ZY, Gruber J, Halliwell B, Gunawan R. Mathematical modeling of the role of mitochondrial fusion and fission in mitochondrial DNA maintenance. PLoS One 2013; 8(10): e76230.
[] [PMID: 24146842]
Figge MT, Reichert AS, Meyer-Hermann M, Osiewacz HD. Deceleration of fusion-fission cycles improves mitochondrial quality control during aging. PLOS Comput Biol 2012; 8(6): e1002576.
[] [PMID: 22761564]
Markevich NI, Hoek JB. Computational modeling analysis of mitochondrial superoxide production under varying substrate conditions and upon inhibition of different segments of the electron transport chain. Biochim Biophys Acta 2015; 1847(6-7): 656-79.
[] [PMID: 25868872]
Passos JF, Nelson G, Wang C, et al. Feedback between p21 and reactive oxygen production is necessary for cell senescence. Mol Syst Biol 2010; 6: 347.
[] [PMID: 20160708]
Dolan DWP, Zupanic A, Nelson G, et al. Integrated stochastic model of DNA Damage Repair by Non-homologous End Joining and p53/p21-mediated early senescence signalling. PLOS Comput Biol 2015; 11(5): e1004246.
[] [PMID: 26020242]
Jonak K, Kurpas M, Szoltysek K, Janus P, Abramowicz A, Puszynski K. A novel mathematical model of ATM/p53/NF- κB pathways points to the importance of the DDR switch-off mechanisms. BMC Syst Biol 2016; 10(1): 75.
[] [PMID: 27526774]
Brännmark C, Nyman E, Fagerholm S, et al. Insulin signaling in type 2 diabetes: experimental and modeling analyses reveal mechanisms of insulin resistance in human adipocytes. J Biol Chem 2013; 288(14): 9867-80.
[] [PMID: 23400783]
Smith GR, Shanley DP. Computational modelling of the regulation of Insulin signalling by oxidative stress. BMC Syst Biol 2013; 7(1): 41.
[] [PMID: 23705851]
Haerter JO, Lövkvist C, Dodd IB, Sneppen K. Collaboration between CpG sites is needed for stable somatic inheritance of DNA methylation states. Nucleic Acids Res 2014; 42(4): 2235-44.
[] [PMID: 24288373]
Santago AC. Conn’s Handbook of Models for Human Aging. 2018.
Collins JJ, Huang C, Hughes S, Kornfeld K. The measurement and analysis of age-related changes in Caenorhabditis elegans. WormBook 2008; 1-21.
[PMID: 18381800]
McGee MD, Weber D, Day N, et al. Loss of intestinal nuclei and intestinal integrity in aging C. elegans. Aging Cell 2011; 10(4): 699-710.
[] [PMID: 21501374]
Hughes SE, Huang C, Kornfeld K. Identification of mutations that delay somatic or reproductive aging of Caenorhabditis elegans. Genetics 2011; 189(1): 341-56.
[] [PMID: 21750263]
Luo S, Kleemann GA, Ashraf JM, Shaw WM, Murphy CT. TGF-β and insulin signaling regulate reproductive aging via oocyte and germline quality maintenance. Cell 2010; 143(2): 299-312.
[] [PMID: 20946987]
Golden TR, Hubbard A, Dando C, Herren MA, Melov S. Age-related behaviors have distinct transcriptional profiles in Caenorhabditis elegans. Aging Cell 2008; 7(6): 850-65.
[] [PMID: 18778409]
Biteau B, Karpac J, Hwangbo D, Jasper H. Regulation of Drosophila lifespan by JNK signaling. Exp Gerontol 2011; 46(5): 349-54.
[] [PMID: 21111799]
Karpac J, Younger A, Jasper H. Dynamic coordination of innate immune signaling and insulin signaling regulates systemic responses to localized DNA damage. Dev Cell 2011; 20(6): 841-54.
[] [PMID: 21664581]
Takeda T, Hosokawa M, Takeshita S, et al. A new murine model of accelerated senescence. Mech Ageing Dev 1981; 17(2): 183-94.
[] [PMID: 7311623]
Edrey YH, Hanes M, Pinto M, Mele J, Buffenstein R. Successful aging and sustained good health in the naked mole rat: a long-lived mammalian model for biogerontology and biomedical research. ILAR J 2011; 52(1): 41-53.
[] [PMID: 21411857]
Keane M, Semeiks J, Webb AE, et al. Insights into the evolution of longevity from the bowhead whale genome. Cell Rep 2015; 10(1): 112-22.
[] [PMID: 25565328]
Bidder GP. Senescence. BMJ 1932; 2(3742): 583-5.
[] [PMID: 20777068]
Comfort A. Effect of delayed and resumed growth on the longevity of a fish [Lebistes reticulatus, Peters] in captivity. Gerontologia 1963; 49: 150-5.
[] [PMID: 14105125]
Lepilina A, Coon AN, Kikuchi K, et al. A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration. Cell 2006; 127(3): 607-19.
[] [PMID: 17081981]
Freeman LM. Cachexia and sarcopenia: emerging syndromes of importance in dogs and cats. J Vet Intern Med 2012; 26(1): 3-17.
[] [PMID: 22111652]
Stacey G. Primary cell cultures and immortal cell lines. eLS 2006.
Schneider EL. Aging and cultured human skin fibroblasts. J Invest Dermatol 1979; 73(1): 15-8.
[] [PMID: 448173]
Schneider EL, Mitsui Y. The relationship between in vitro cellular aging and in vivo human age. Proc Natl Acad Sci USA 1976; 73(10): 3584-8.
[] [PMID: 1068470]
Bradley MO, Sharkey NA. Mutagenicity and toxicity of visible fluorescent light to cultured mammalian cells. Nature 1977; 266(5604): 724-6.
[] [PMID: 876351]
Wang RJ. Effect of room fluorescent light on the deterioration of tissue culture medium. in vitro 1976; 12(1): 19-22.
[] [PMID: 1244326]
Frippiat C, Chen QM, Remacle J, Toussaint O. Cell cycle regulation in H(2)O(2)-induced premature senescence of human diploid fibroblasts and regulatory control exerted by the papilloma virus E6 and E7 proteins. Exp Gerontol 2000; 35(6-7): 733-45.
[] [PMID: 11053664]
Dumont P, Burton M, Chen QM, et al. Induction of replicative senescence biomarkers by sublethal oxidative stresses in normal human fibroblast. Free Radic Biol Med 2000; 28(3): 361-73.
[] [PMID: 10699747]
Ma W, Wlaschek M, Hommel C, Schneider L-A, Scharffetter-Kochanek K. Psoralen plus UVA (PUVA) induced premature senescence as a model for stress-induced premature senescence. Exp Gerontol 2002; 37(10-11): 1197-201.
[] [PMID: 12470831]
Seidita G, Polizzi D, Costanzo G, Costa S, Di Leonardo A. Differential gene expression in p53-mediated G(1) arrest of human fibroblasts after γ-irradiation or N-phosphoacetyl-L-aspartate treatment. Carcinogenesis 2000; 21(12): 2203-10.
[] [PMID: 11133809]
Hadley EC, Kress ED, Cristofalo VJ. Trypsinization frequency and loss of proliferative capacity in WI-38 cells. J Gerontol 1979; 34(2): 170-6.
[] [PMID: 438470]
Cristofalo VJ, Beck J, Allen RG. Commentary: cell senescence: An evaluation of replicative senescence in culture as a model for cell aging in situ. J Gerontol 2003; 58(9): B776-9.
Martin GM, Sprague CA, Epstein CJ. Replicative life-span of cultivated human cells. Effects of donor’s age, tissue, and genotype. Lab Invest 1970; 23(1): 86-92.
[PMID: 5431223]
León Z, García-Cañaveras JC, Donato MT, Lahoz A. Mammalian cell metabolomics: experimental design and sample preparation. Electrophoresis 2013; 34(19): 2762-75.
[] [PMID: 23436493]
Panopoulos AD, Yanes O, Ruiz S, et al. The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. Cell Res 2012; 22(1): 168-77.
[] [PMID: 22064701]
Chrysanthopoulos PK, Goudar CT, Klapa MI. Metabolomics for high-resolution monitoring of the cellular physiological state in cell culture engineering. Metab Eng 2010; 12(3): 212-22.
[] [PMID: 19914390]
Jennen D, Ruiz-Aracama A, Magkoufopoulou C, et al. Integrating transcriptomics and metabonomics to unravel modes-of-action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in HepG2 cells. BMC Syst Biol 2011; 5: 139.
[] [PMID: 21880148]
Campisi J, Warner HR. Aging in mitotic and post-mitotic cells. Adv Cell Aging Gerontol. Elsevier 2001; pp. 1-16.
Baker DJ, Childs BG, Durik M, et al. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature 2016; 530(7589): 184-9.
[] [PMID: 26840489]
Childs BG, Baker DJ, Wijshake T, Conover CA, Campisi J, van Deursen JM. Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science 2016; 354(6311): 472-7.
[] [PMID: 27789842]
Chang J, Wang Y, Shao L, et al. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat Med 2016; 22(1): 78-83.
[] [PMID: 26657143]
Jung T, Bader N, Grune T. Lipofuscin: formation, distribution, and metabolic consequences. Ann N Y Acad Sci 2007; 1119(1): 97-111.
[] [PMID: 18056959]
Reichel W, Hollander J, Clark JH, Strehler BL. Lipofuscin pigment accumulation as a function of age and distribution in rodent brain. J Gerontol 1968; 23(1): 71-8.
[] [PMID: 5635799]
Sitte N, Merker K, Grune T, von Zglinicki T. Lipofuscin accumulation in proliferating fibroblasts in vitro: an indicator of oxidative stress. Exp Gerontol 2001; 36(3): 475-86.
[] [PMID: 11250119]
Georgakopoulou EA, Tsimaratou K, Evangelou K, et al. Specific lipofuscin staining as a novel biomarker to detect replicative and stress-induced senescence. A method applicable in cryo-preserved and archival tissues. Aging (Albany NY) 2013; 5(1): 37-50.
[] [PMID: 23449538]
Ishikawa S, Ishikawa F. Proteostasis failure and cellular senescence in long-term cultured postmitotic rat neurons. Aging Cell 2020; 19(1): e13071.
[] [PMID: 31762159]
McHugh D, Gil J. Senescence and aging: Causes, consequences, and therapeutic avenues. J Cell Biol 2018; 217(1): 65-77.
[] [PMID: 29114066]
Bayreuther K, Rodemann HP, Hommel R, Dittmann K, Albiez M, Francz PI. Human skin fibroblasts in vitro differentiate along a terminal cell lineage. Proc Natl Acad Sci USA 1988; 85(14): 5112-6.
[] [PMID: 3393534]
Alcorta DA, Xiong Y, Phelps D, Hannon G, Beach D, Barrett JC. Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proc Natl Acad Sci USA 1996; 93(24): 13742-7.
[] [PMID: 8943005]
Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 1999; 13(12): 1501-12.
[] [PMID: 10385618]
Dimri GP, Lee X, Basile G, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 1995; 92(20): 9363-7.
[] [PMID: 7568133]
d’Adda di Fagagna F, Reaper P, Clay-Farrace L, Fiegler H, Carr P, Zglinicki T, et al. DNA damage checkpoint response in telomere-initiated senescence. Nature 426: 194-198. Nature 2003; 426: 194-8.
[] [PMID: 14608368]
Freund A, Laberge R-M, Demaria M, Campisi J. Lamin B1 loss is a senescence-associated biomarker. Mol Biol Cell 2012; 23(11): 2066-75.
[] [PMID: 22496421]
Ressler S, Bartkova J, Niederegger H, et al. p16INK4A is a robust in vivo biomarker of cellular aging in human skin. Aging Cell 2006; 5(5): 379-89.
[] [PMID: 16911562]
Debacq-Chainiaux F, Ben Ameur R, Bauwens E, Dumortier E, Toutfaire M, Toussaint O. Stress-induced [Premature] Senescence. Cellular Ageing and Replicative Senescence. Cham: Springer International Publishing 2016; pp. 243-62.
Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 1997; 88(5): 593-602.
[] [PMID: 9054499]
Ogryzko VV, Hirai TH, Russanova VR, Barbie DA, Howard BH. Human fibroblast commitment to a senescence-like state in response to histone deacetylase inhibitors is cell cycle dependent. Mol Cell Biol 1996; 16(9): 5210-8.
[] [PMID: 8756678]
Robles SJ, Adami GR. Agents that cause DNA double strand breaks lead to p16INK4a enrichment and the premature senescence of normal fibroblasts. Oncogene 1998; 16(9): 1113-23.
[] [PMID: 9528853]
Parrinello S, Samper E, Krtolica A, Goldstein J, Melov S, Campisi J. Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat Cell Biol 2003; 5(8): 741-7.
[] [PMID: 12855956]
Denchi EL, de Lange T. Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature 2007; 448(7157): 1068-71.
[] [PMID: 17687332]
Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature 1990; 345(6274): 458-60.
[] [PMID: 2342578]
Beauséjour CM, Krtolica A, Galimi F, et al. Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J 2003; 22(16): 4212-22.
[] [PMID: 12912919]
Coppé J-P, Patil CK, Rodier F, et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 2008; 6(12): 2853-68.
[] [PMID: 19053174]
Murillo-Ortiz B, Albarrán-Tamayo F, López-Briones S, Martínez-Garza S, Benítez-Bribiesca L, Arenas-Aranda D. Increased telomere length and proliferative potential in peripheral blood mononuclear cells of adults of different ages stimulated with concanavalin A. BMC Geriatr 2013; 13(1): 99.
[] [PMID: 24063536]
Redaelli S, Bentivegna A, Foudah D, et al. From cytogenomic to epigenomic profiles: monitoring the biologic behavior of in vitro cultured human bone marrow mesenchymal stem cells. Stem Cell Res Ther 2012; 3(6): 47.
[] [PMID: 23168092]
Alt EU, Senst C, Murthy SN, et al. Aging alters tissue resident mesenchymal stem cell properties. Stem Cell Res (Amst) 2012; 8(2): 215-25.
[] [PMID: 22265741]
Rübe CE, Fricke A, Widmann TA, et al. Accumulation of DNA damage in hematopoietic stem and progenitor cells during human aging. PLoS One 2011; 6(3): e17487.
[] [PMID: 21408175]
James EL, Michalek RD, Pitiyage GN, et al. Senescent human fibroblasts show increased glycolysis and redox homeostasis with extracellular metabolomes that overlap with those of irreparable DNA damage, aging, and disease. J Proteome Res 2015; 14(4): 1854-71.
[] [PMID: 25690941]
James EL, Lane JAE, Michalek RD, Karoly ED, Parkinson EK. Replicatively senescent human fibroblasts reveal a distinct intracellular metabolic profile with alterations in NAD+ and nicotinamide metabolism. Sci Rep 2016; 6: 38489.
[] [PMID: 27924925]
Eberhardt K, Matthäus C, Marthandan S, Diekmann S, Popp J. Raman and infrared spectroscopy reveal that proliferating and quiescent human fibroblast cells age by biochemically similar but not identical processes. PLoS One 2018; 13(12): e0207380-.
Gey C, Seeger K. Metabolic changes during cellular senescence investigated by proton NMR-spectroscopy. Mech Ageing Dev 2013; 134(3-4): 130-8.
[] [PMID: 23416267]
Toussaint O, Houbion A, Remacle J. Aging as a multi-step process characterized by a lowering of entropy production leading the cell to a sequence of defined stages. II. Testing some predictions on aging human fibroblasts in culture. Mech Ageing Dev 1992; 65(1): 65-83.
[] [PMID: 1405791]
von Zglinicki T, Pilger R, Sitte N. Accumulation of single-strand breaks is the major cause of telomere shortening in human fibroblasts. Free Radic Biol Med 2000; 28(1): 64-74.
[] [PMID: 10656292]
Chen J, Brodsky SV, Goligorsky DM, et al. Glycated collagen I induces premature senescence-like phenotypic changes in endothelial cells. Circ Res 2002; 90(12): 1290-8.
[] [PMID: 12089067]
Rudolf E, Rezáčová K, Červinka M. Activation of p38 and changes in mitochondria accompany autophagy to premature senescence-like phenotype switch upon chronic exposure to selenite in colon fibroblasts. Toxicol Lett 2014; 231(1): 29-37.
[] [PMID: 25204997]
Toussaint O, Medrano EE, von Zglinicki T. Cellular and molecular mechanisms of stress-induced premature senescence (SIPS) of human diploid fibroblasts and melanocytes. Exp Gerontol 2000; 35(8): 927-45.
[] [PMID: 11121681]
Ott C, Jung T, Grune T, Höhn A. SIPS as a model to study age-related changes in proteolysis and aggregate formation. Mech Ageing Dev 2018; 170: 72-81.
[] [PMID: 28755850]
Toussaint O, Remacle J, Dierick J-F, et al. From the Hayflick mosaic to the mosaics of ageing. Role of stress-induced premature senescence in human ageing. Int J Biochem Cell Biol 2002; 34(11): 1415-29.
[] [PMID: 12200036]
Bielak-Zmijewska A, Wnuk M, Przybylska D, et al. A comparison of replicative senescence and doxorubicin-induced premature senescence of vascular smooth muscle cells isolated from human aorta. Biogerontology 2014; 15(1): 47-64.
[] [PMID: 24243065]
Von Zglinicki T. Replicative senescence and the art of counting. Exp Gerontol 2003; 38(11-12): 1259-64.
[] [PMID: 14698805]
Toussaint O, Dumont P, Remacle J, et al. Stress-induced premature senescence or stress-induced senescence-like phenotype: one in vivo reality, two possible definitions? Sci World J 2002; 2: 230-47.
[] [PMID: 12806055]
Xu D, Neville R, Finkel T. Homocysteine accelerates endothelial cell senescence. FEBS Lett 2000; 470(1): 20-4.
[] [PMID: 10722838]
Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965; 37(3): 614-36.
[] [PMID: 14315085]
Kohn RR. Aging and cell division. Science 1975; 188(4185): 203-4.
[] [PMID: 17800380]
Hayflick L. The cell biology of aging.
Le Guilly Y. Long-term culture of human adult liver cells: morphological changes related to in vitro senescence and effect of donor's age on growth potential. Gerontology 1973; 19(5-6): 303-13.
Macedo JC, Vaz S, Bakker B, et al. FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence. Nat Commun 2018; 9(1): 2834.
[] [PMID: 30026603]
Hu JL, Todhunter ME, LaBarge MA, Gartner ZJ. Opportunities for organoids as new models of aging. J Cell Biol 2018; 217(1): 39-50.
[] [PMID: 29263081]
Barkauskas CE, Chung M-I, Fioret B, Gao X, Katsura H, Hogan BLM. Lung organoids: current uses and future promise. Development 2017; 144(6): 986-97.
[] [PMID: 28292845]
Chaudhuri AR, de Waal EM, Pierce A, Van Remmen H, Ward WF, Richardson A. Detection of protein carbonyls in aging liver tissue: A fluorescence-based proteomic approach. Mech Ageing Dev 2006; 127(11): 849-61.
[] [PMID: 17002888]
Jung T, Höhn A, Grune T. Lipofuscin: Detection and quantification by microscopic techniques.Advanced Protocols in Oxidative Stress II. Totowa, NJ: Humana Press 2010; pp. 173-93.
Sato T, van Es JH, Snippert HJ, et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 2011; 469(7330): 415-8.
[] [PMID: 21113151]
Nguyen-Ngoc K-V, Shamir ER, Huebner RJ, Beck JN, Cheung KJ, Ewald AJ. 3D Culture assays of murine mammary branching morphogenesis and epithelial invasion.Tissue Morphogenesis: Methods and Protocols. New York, NY: Springer New York 2015; pp. 135-62.
Jones MJ, Goodman SJ, Kobor MS. DNA methylation and healthy human aging. Aging Cell 2015; 14(6): 924-32.
[] [PMID: 25913071]
Blokzijl F, de Ligt J, Jager M, et al. Tissue-specific mutation accumulation in human adult stem cells during life. Nature 2016; 538(7624): 260-4.
[] [PMID: 27698416]
Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: a review. Diabetologia 2001; 44(2): 129-46.
[] [PMID: 11270668]
Caughey B, Lansbury PT. Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. Annu Rev Neurosci 2003; 26(1): 267-98.
[] [PMID: 12704221]
Hayton S, Maker GL, Mullaney I, Trengove RD. Experimental design and reporting standards for metabolomics studies of mammalian cell lines. Cell Mol Life Sci 2017; 74(24): 4421-41.
[] [PMID: 28669031]
van der Werf MJ, Takors R, Smedsgaard J, et al. Standard reporting requirements for biological samples in metabolomics experiments: microbial and in vitro biology experiments. Metabolomics 2007; 3: 189-94.
[] [PMID: 25653575]
Lindon JC, Nicholson JK, Holmes E, et al. Summary recommendations for standardization and reporting of metabolic analyses. Nat Biotechnol 2005; 23(7): 833-8.
[] [PMID: 16003371]
Cuperlović-Culf M, Barnett DA, Culf AS, Chute I. Cell culture metabolomics: applications and future directions. Drug Discov Today 2010; 15(15-16): 610-21.
[] [PMID: 20601091]
Muschet C, Möller G, Prehn C, de Angelis MH, Adamski J, Tokarz J. Removing the bottlenecks of cell culture metabolomics: fast normalization procedure, correlation of metabolites to cell number, and impact of the cell harvesting method. Metabolomics 2016; 12(10): 151.
[] [PMID: 27729828]
Phipps SM, Berletch JB, Andrews LG, Tollefsbol TO. Aging cell culture: methods and observations. Methods Mol Biol 2007; 371: 9-19.
[] [PMID: 17634570]
Ma S, Upneja A, Galecki A, et al. Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity. eLife 2016; 5: 5.
[] [PMID: 27874830]
Sreekumar A, Poisson LM, Rajendiran TM, et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 2009; 457(7231): 910-4.
[] [PMID: 19212411]
Lin J, Yi X, Zhuang Y. Medium optimization based on comparative metabolomic analysis of chicken embryo fibroblast DF-1 cells. RSC Advances 2019; 9(47): 27369-77.
Creek DJ, Nijagal B, Kim D-H, Rojas F, Matthews KR, Barrett MP. Metabolomics guides rational development of a simplified cell culture medium for drug screening against Trypanosoma brucei. Antimicrob Agents Chemother 2013; 57(6): 2768-79.
[] [PMID: 23571546]
Shedd SF, Lutz NW, Hull WE. The influence of medium formulation on phosphomonoester and UDP-hexose levels in cultured human colon tumor cells as observed by 31P NMR spectroscopy. NMR Biomed 1993; 6(4): 254-63.
[] [PMID: 8217527]
Rocha A, Magalhães S, Nunes A. Study aging by fibroblasts metabolome. Curr Mol Med 2020.
[] [PMID: 32867636]

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