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Current Stem Cell Research & Therapy

Author(s): Peter Hollands* and Todd Ovokaitys

DOI: 10.2174/1574888X18666230208102635

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New Concepts in the Manipulation of the Aging Process

Page: [178 - 184] Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

This review explores the current concepts in aging and then goes on to describe a novel, ground-breaking technology which will change the way we think about and manage aging. The foundation of the review is based on the work carried out on the QiLaser activation of human Very Small Embryonic Like (hVSEL) pluripotent stem cells in autologous Platelet Rich Plasma (PRP), known as the Qigeneration Procedure. The application of this technology in anti-aging technology is discussed with an emphasis on epigenetic changes during aging focusing on DNA methylation.

[1]
McCay CM, Crowell MF, Maynard LA. The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. Nutrition 1989; 5(3): 155-71.
[PMID: 2520283]
[2]
Thorley M, Malatras A, Duddy W, et al. Changes in communication between muscle stem cells and their environment with aging. J Neuromuscul Dis 2015; 2(3): 205-17.
[http://dx.doi.org/10.3233/JND-150097] [PMID: 27858742]
[3]
Sameri S, Samadi P, Dehghan R, Salem E, Fayazi N, Amini R. Stem cell aging in lifespan and disease: A state-of-the-art review. Curr Stem Cell Res Ther 2020; 15(4): 362-78.
[http://dx.doi.org/10.2174/1574888X15666200213105155] [PMID: 32053079]
[4]
Kasapoğlu I, Seli E. Mitochondrial dysfunction and ovarian aging. Endocrinology 2020; 161(2): bqaa001.
[http://dx.doi.org/10.1210/endocr/bqaa001] [PMID: 31927571]
[5]
Sen P, Shah PP, Nativio R, Berger SL. Epigenetic mechanisms of longevity and aging. Cell 2016; 166(4): 822-39.
[http://dx.doi.org/10.1016/j.cell.2016.07.050] [PMID: 27518561]
[6]
Zhu Y, Liu X, Ding X, Wang F, Geng X. Telomere and its role in the aging pathways: telomere shortening, cell senescence and mitochondria dysfunction. Biogerontology 2019; 20(1): 1-16.
[http://dx.doi.org/10.1007/s10522-018-9769-1] [PMID: 30229407]
[7]
Klaips CL, Jayaraj GG, Hartl FU. Pathways of cellular proteostasis in aging and disease. J Cell Biol 2018; 217(1): 51-63.
[http://dx.doi.org/10.1083/jcb.201709072] [PMID: 29127110]
[8]
Niedernhofer LJ, Gurkar AU, Wang Y, Vijg J, Hoeijmakers JHJ, Robbins PD. Nuclear genomic instability and aging. Annu Rev Biochem 2018; 87(1): 295-322.
[http://dx.doi.org/10.1146/annurev-biochem-062917-012239] [PMID: 29925262]
[9]
Ullrich NJ, Gordon LB. Hutchinson–Gilford progeria syndrome. Handb Clin Neurol 2015; 132: 249-64.
[http://dx.doi.org/10.1016/B978-0-444-62702-5.00018-4] [PMID: 26564085]
[10]
Luxton JJ, Bailey SM. Twins, telomeres, and aging-in space! Plast Reconstr Surg 2021 January; 147(1S-2): 7S-14S.
[http://dx.doi.org/10.1097/PRS.0000000000007616] [PMID: 33347069]
[11]
Nwanaji-Enwerem JC, Nwanaji-Enwerem U, Van Der Laan L, Galazka JM, Redeker NS, Cardenas A. A longitudinal epigenetic aging and leukocyte analysis of simulated space travel: The Mars-500 Mission. Cell Rep 2020; 33(10): 108406.
[http://dx.doi.org/10.1016/j.celrep.2020.108406] [PMID: 33242403]
[12]
Sibonga JD. Spaceflight-induced bone loss: Is there an osteoporosis risk? Curr Osteoporos Rep 2013; 11(2): 92-8.
[http://dx.doi.org/10.1007/s11914-013-0136-5] [PMID: 23564190]
[13]
Rittweger J, Gunga HC, Felsenberg D, Kirsch KA. Muscle and bone-aging and space. J Gravit Physiol 1999; 6(1): 133-6.
[PMID: 11542992]
[14]
Hughson RL, Helm A, Durante M. Heart in space: effect of the extraterrestrial environment on the cardiovascular system. Nat Rev Cardiol 2018; 15(3): 167-80.
[http://dx.doi.org/10.1038/nrcardio.2017.157] [PMID: 29053152]
[15]
Nakamura-Ishizu A, Ito K, Suda T. Hematopoietic stem cell metabolism during development and aging. Dev Cell 2020; 54(2): 239-55.
[http://dx.doi.org/10.1016/j.devcel.2020.06.029] [PMID: 32693057]
[16]
Morganti C, Ito K. Mitochondrial contributions to hematopoietic stem cell aging. Int J Mol Sci 2021; 22(20): 11117.
[http://dx.doi.org/10.3390/ijms222011117] [PMID: 34681777]
[17]
Klepin HD. Myelodysplastic syndromes and acute myeloid leukemia in the elderly. Clin Geriatr Med 2016; 32(1): 155-73.
[http://dx.doi.org/10.1016/j.cger.2015.08.010] [PMID: 26614866]
[18]
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 2013; 153(6): 1194-217.
[http://dx.doi.org/10.1016/j.cell.2013.05.039] [PMID: 23746838]
[19]
Fang EF, Lautrup S, Hou Y, et al. NAD+ in aging: Molecular mechanisms and translational implications. Trends Mol Med 2017; 23(10): 899-916.
[http://dx.doi.org/10.1016/j.molmed.2017.08.001] [PMID: 28899755]
[20]
Chong A, Malavasi F, Israel S, et al. ADP ribosyl-cyclases (CD38/CD157), social skills and friendship. Psychoneuroendocrinology 2017; 78: 185-92.
[http://dx.doi.org/10.1016/j.psyneuen.2017.01.011] [PMID: 28212520]
[21]
Jiang Y, Liu T, Lee CH, Chang Q, Yang J, Zhang Z. The NAD+-mediated self-inhibition mechanism of pro-neurodegenerative SARM1. Nature 2020; 588(7839): 658-63.
[http://dx.doi.org/10.1038/s41586-020-2862-z] [PMID: 33053563]
[22]
Sambashivan S, Freeman MR. SARM1 signaling mechanisms in the injured nervous system. Curr Opin Neurobiol 2021; 69: 247-55.
[http://dx.doi.org/10.1016/j.conb.2021.05.004] [PMID: 34175654]
[23]
Li N, Wang Y, Deng W, Lin SH. Poly (ADP-Ribose) Polymerases (PARPs) and PARP inhibitor-targeted therapeutics. Anticancer Agents Med Chem 2019; 19(2): 206-12.
[http://dx.doi.org/10.2174/1871520618666181109164645] [PMID: 30417796]
[24]
Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol 2014; 24(8): 464-71.
[http://dx.doi.org/10.1016/j.tcb.2014.04.002] [PMID: 24786309]
[25]
Katsyuba E, Romani M, Hofer D, Auwerx J. NAD+ homeostasis in health and disease. Nat Metab 2020; 2(1): 9-31.
[http://dx.doi.org/10.1038/s42255-019-0161-5] [PMID: 32694684]
[26]
Lautrup S, Sinclair DA, Mattson MP, Fang EF. NAD+ in brain aging and neurodegenerative disorders. Cell Metab 2019; 30(4): 630-55.
[http://dx.doi.org/10.1016/j.cmet.2019.09.001] [PMID: 31577933]
[27]
Yang B, Dan X, Hou Y, et al. NAD+ supplementation prevents STING‐induced senescence in ataxia telangiectasia by improving mitophagy. Aging Cell 2021; 20(4): e13329.
[http://dx.doi.org/10.1111/acel.13329] [PMID: 33734555]
[28]
Okur MN, Mao B, Kimura R, et al. Short-term NAD+ supplementation prevents hearing loss in mouse models of Cockayne syndrome. NPJ Aging Mech Dis 2020; 6(1): 1-17.
[http://dx.doi.org/10.1038/s41514-019-0040-z] [PMID: 31934345]
[29]
Fang EF, Scheibye-Knudsen M, Brace LE, et al. Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction. Cell 2014; 157(4): 882-96.
[http://dx.doi.org/10.1016/j.cell.2014.03.026] [PMID: 24813611]
[30]
Teslaa T, Teitell MA. Pluripotent stem cell energy metabolism: an update. EMBO J 2015; 34(2): 138-53.
[http://dx.doi.org/10.15252/embj.201490446] [PMID: 25476451]
[31]
Lindauer M, Hochhaus A. Dasatinib. Recent Results Cancer Res 2018; 212: 29-68.
[http://dx.doi.org/10.1007/978-3-319-91439-8_2] [PMID: 30069624]
[32]
Hosseini A, Razavi BM, Banach M, Hosseinzadeh H. Quercetin and metabolic syndrome: A review. Phytother Res 2021; 35(10): 5352-64.
[http://dx.doi.org/10.1002/ptr.7144] [PMID: 34101925]
[33]
Yousefzadeh MJ, Zhu Y, McGowan SJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine 2018; 36: 18-28.
[http://dx.doi.org/10.1016/j.ebiom.2018.09.015] [PMID: 30279143]
[34]
Ogrodnik M, Zhu Y, Langhi LGP, et al. Obesity-induced cellular senescence drives anxiety and impairs neurogenesis. Cell Metab 2019; 29(5): 1061-1077.e8.
[http://dx.doi.org/10.1016/j.cmet.2018.12.008] [PMID: 30612898]
[35]
Sturmlechner I, Durik M, Sieben CJ, Baker DJ, van Deursen JM. Cellular senescence in renal ageing and disease. Nat Rev Nephrol 2017; 13(2): 77-89.
[http://dx.doi.org/10.1038/nrneph.2016.183] [PMID: 28029153]
[36]
Palmer AK, Gustafson B, Kirkland J. L, Smith U. Cellular senescence: At the nexus between aging and diabetes. Diabetologia 2019; 62(10): 1835-41.
[http://dx.doi.org/10.1007/s00125-019-4934-x] [PMID: 31451866]
[37]
Martel J, Ojcius DM, Wu CY, et al. Emerging use of senolytics and senomorphics against aging and chronic diseases. Med Res Rev 2020; 40(6): 2114-31.
[http://dx.doi.org/10.1002/med.21702] [PMID: 32578904]
[38]
Derosa G, Maffioli P, D’Angelo A, Di Pierro F. A role for quercetin in coronavirus disease 2019 (COVID‐19). Phytother Res 2021; 35(3): 1230-6.
[http://dx.doi.org/10.1002/ptr.6887] [PMID: 33034398]
[39]
Igelmann S, Lessard F, Uchenunu O, et al. A hydride transfer complex reprograms NAD metabolism and bypasses senescence. Mol Cell 2021; 81(18): 3848-3865.e19.
[http://dx.doi.org/10.1016/j.molcel.2021.08.028] [PMID: 34547241]
[40]
Liu N, Wu YG, Lan GC, et al. Pyruvate prevents aging of mouse oocytes. Reproduction 2009; 138(2): 223-34.
[http://dx.doi.org/10.1530/REP-09-0122] [PMID: 19465488]
[41]
Marín-Briggiler CI, Luque GM, Gervasi MG, et al. Human sperm remain motile after a temporary energy restriction but do not undergo capacitation-related events. Front Cell Dev Biol 2021; 9: 777086.
[http://dx.doi.org/10.3389/fcell.2021.777086] [PMID: 34869380]
[42]
Xella S, Marsella T, Tagliasacchi D, et al. Embryo quality and implantation rate in two different culture media: ISM1 versus Universal IVF Medium. Fertil Steril 2010; 93(6): 1859-63.
[http://dx.doi.org/10.1016/j.fertnstert.2008.12.030] [PMID: 19152877]
[43]
Zhou FQ. NAD+, senolytics, or pyruvate for healthy aging? Nutr Metab Insights 2021; 14: 11786388211053407.
[http://dx.doi.org/10.1177/11786388211053407] [PMID: 34720589]
[44]
Zuccoli GS, Guest PC, Martins-de-Souza D. Effects on Glial Cell Glycolysis in Schizophrenia: An Advanced Aging Phenotype? Adv Exp Med Biol 2019; 1178: 25-38.
[http://dx.doi.org/10.1007/978-3-030-25650-0_2] [PMID: 31493220]
[45]
Kim JY, Lee SH, Bae IH, et al. Pyruvate protects against cellular senescence through the control of mitochondrial and lysosomal function in dermal fibroblasts. J Invest Dermatol 2018; 138(12): 2522-30.
[http://dx.doi.org/10.1016/j.jid.2018.05.033] [PMID: 29959907]
[46]
Park JT, Lee YS, Cho KA, Park SC. Adjustment of the lysosomal-mitochondrial axis for control of cellular senescence. Ageing Res Rev 2018; 47: 176-82.
[http://dx.doi.org/10.1016/j.arr.2018.08.003] [PMID: 30142381]
[47]
Sabatini DM, Erdjument-Bromage H, Lui M, Tempst P, Snyder SH. RAFT1: A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell 1994; 78(1): 35-43.
[http://dx.doi.org/10.1016/0092-8674(94)90570-3] [PMID: 7518356]
[48]
Brown EJ, Albers MW, Bum Shin T, et al. A mammalian protein targeted by G1-arresting rapamycin–receptor complex. Nature 1994; 369(6483): 756-8.
[http://dx.doi.org/10.1038/369756a0] [PMID: 8008069]
[49]
Sabers CJ, Martin MM, Brunn GJ, et al. Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells. J Biol Chem 1995; 270(2): 815-22.
[http://dx.doi.org/10.1074/jbc.270.2.815] [PMID: 7822316]
[50]
Liu GY, Sabatini DM. mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol 2020; 21(4): 183-203.
[http://dx.doi.org/10.1038/s41580-019-0199-y] [PMID: 31937935]
[51]
Wolfson RL, Sabatini DM. The Dawn of the Age of Amino Acid Sensors for the mTORC1 Pathway. Cell Metab 2017; 26(2): 301-9.
[http://dx.doi.org/10.1016/j.cmet.2017.07.001] [PMID: 28768171]
[52]
Gwinn DM, Shackelford DB, Egan DF, et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 2008; 30(2): 214-26.
[http://dx.doi.org/10.1016/j.molcel.2008.03.003] [PMID: 18439900]
[53]
Wu JJ, Liu J, Chen EB, et al. Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression. Cell Rep 2013; 4(5): 913-20.
[54]
Chen C, Liu Y, Liu Y, Zheng P. mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci Signal 2009; 2(98): ra75.
[http://dx.doi.org/10.1126/scisignal.2000559] [PMID: 19934433]
[55]
Yilmaz ÖH, Katajisto P, Lamming DW, et al. mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake. Nature 2012; 486(7404): 490-5.
[http://dx.doi.org/10.1038/nature11163] [PMID: 22722868]
[56]
Mannick JB, Morris M, Hockey HP, et al. TORC1 inhibition enhances immune function and reduces infections in the elderly. Sci Transl Med 2018; 10(449): eaaq1564.
[57]
Hambright WS, Philippon MJ, Huard J. Rapamycin for aging stem cells. Aging (Albany NY) 2020; 12(15): 15184-5.
[http://dx.doi.org/10.18632/aging.103816] [PMID: 32756013]
[58]
Osman C, Jennings R, El-Ghariani K, Pinto A. Plasma exchange in neurological disease. Pract Neurol 2020; 20(2): 92-9.
[http://dx.doi.org/10.1136/practneurol-2019-002336] [PMID: 31300488]
[59]
Boada M, Ramos-Fernández E, Guivernau B, et al. Treatment of Alzheimer disease using combination therapy with plasma exchange and haemapheresis with albumin and intravenous immunoglobulin: Rationale and treatment approach of the AMBAR (Alzheimer Management By Albumin Replacement) study. Neurologia 2016; 31(7): 473-81.
[http://dx.doi.org/10.1016/j.nrl.2014.02.003] [PMID: 25023458]
[60]
Li X, Zhang J, Sun C, et al. Application of biological age assessment of Chinese population in potential anti-ageing technology. Immun Ageing 2018; 15(1): 33.
[http://dx.doi.org/10.1186/s12979-018-0140-9] [PMID: 30574171]
[61]
Rea IM, Gibson DS, McGilligan V, McNerlan SE, Alexander HD, Ross OA. Age and age-related diseases: Role of inflammation triggers and cytokines. Front Immunol 2018; 9: 586.
[http://dx.doi.org/10.3389/fimmu.2018.00586] [PMID: 29686666]
[62]
Mattson MP, Longo VD, Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Res Rev 2017; 39: 46-58.
[http://dx.doi.org/10.1016/j.arr.2016.10.005] [PMID: 27810402]
[63]
Stekovic S, Hofer SJ, Tripolt N, et al. Alternate day fasting improves physiological and molecular markers of aging in healthy, non-obese humans. Cell Metab 2019; 30(3): 462-476.e6.
[http://dx.doi.org/10.1016/j.cmet.2019.07.016] [PMID: 31471173]
[64]
Horvath S. DNA methylation age of human tissues and cell types. Genome Biol 2013; 14(10): R115.
[http://dx.doi.org/10.1186/gb-2013-14-10-r115] [PMID: 24138928]
[65]
Hannum G, Guinney J, Zhao L, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell 2013; 49(2): 359-67.
[http://dx.doi.org/10.1016/j.molcel.2012.10.016] [PMID: 23177740]
[66]
Weidner C, Lin Q, Koch C, et al. Aging of blood can be tracked by DNA methylation changes at just three CpG sites. Genome Biol 2014; 15(2): R24.
[http://dx.doi.org/10.1186/gb-2014-15-2-r24] [PMID: 24490752]
[67]
Levine ME, Lu AT, Quach A, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY) 2018; 10(4): 573-91.
[http://dx.doi.org/10.18632/aging.101414] [PMID: 29676998]
[68]
Horvath S, Raj K. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet 2018; 19(6): 371-84.
[http://dx.doi.org/10.1038/s41576-018-0004-3] [PMID: 29643443]
[69]
Fuchs E, Chen T. A matter of life and death: Self‐renewal in stem cells. EMBO Rep 2013; 14(1): 39-48.
[http://dx.doi.org/10.1038/embor.2012.197] [PMID: 23229591]
[70]
Fliedner TM. The role of blood stem cells in hematopoietic cell renewal. Stem Cells 1998; 16 (Suppl. 1): 13-29.
[http://dx.doi.org/10.1002/stem.5530160805] [PMID: 11012145]
[71]
Steensma DP, Kyle RA. James Till and Ernest McCulloch: Hematopoietic stem cell discoverers. Mayo Clin Proc 2021; 96(3): 830-1.
[http://dx.doi.org/10.1016/j.mayocp.2021.01.016] [PMID: 33673940]
[72]
Ding DC, Shyu WC, Lin SZ. Mesenchymal stem cells. Cell Transplant 2011; 20(1): 5-14.
[http://dx.doi.org/10.3727/096368910X] [PMID: 21396235]
[73]
Samsonraj RM, Raghunath M, Nurcombe V, Hui JH, van Wijnen AJ, Cool SM. Multifaceted characterization of human mesenchymal stem cells for use in regenerative medicine. Stem Cells Transl Med 2017; 6(12): 2173-85.
[http://dx.doi.org/10.1002/sctm.17-0129] [PMID: 29076267]
[74]
Campbell A, Brieva T, Raviv L, et al. Concise Review: Process development considerations for cell therapy. Stem Cells Transl Med 2015; 4(10): 1155-63.
[http://dx.doi.org/10.5966/sctm.2014-0294] [PMID: 26315572]
[75]
Zarei F, Abbaszadeh A. Application of cell therapy for anti-aging facial skin. Curr Stem Cell Res Ther 2019; 14(3): 244-8.
[http://dx.doi.org/10.2174/1574888X13666181113113415] [PMID: 30421684]
[76]
Lee BC, Yu KR. Impact of mesenchymal stem cell senescence on inflammaging. BMB Rep 2020; 53(2): 65-73.
[http://dx.doi.org/10.5483/BMBRep.2020.53.2.291] [PMID: 31964472]
[77]
Neri S, Borzì R. Molecular mechanisms contributing to mesenchymal stromal cell aging. Biomolecules 2020; 10(2): 340.
[http://dx.doi.org/10.3390/biom10020340] [PMID: 32098040]
[78]
Ma Y, Qi M, An Y, et al. Autophagy controls mesenchymal stem cell properties and senescence during bone aging. Aging Cell 2018; 17(1): e12709.
[http://dx.doi.org/10.1111/acel.12709] [PMID: 29210174]
[79]
Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 2014; 30(1): 255-89.
[http://dx.doi.org/10.1146/annurev-cellbio-101512-122326] [PMID: 25288114]
[80]
Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science 2020; 367(6478): eaau6977.
[http://dx.doi.org/10.1126/science.aau6977] [PMID: 32029601]
[81]
Ha DH, Kim H, Lee J, et al. Mesenchymal stem/stromal cell-derived exosomes for immunomodulatory therapeutics and skin regeneration. Cells 2020; 9(5): 1157.
[http://dx.doi.org/10.3390/cells9051157] [PMID: 32392899]
[82]
Yoshida M, Satoh A, Lin JB, et al. Extracellular vesicle-contained enampt delays aging and extends lifespan in mice. Cell Metab 2019; 30(2): 329-342.e5.
[http://dx.doi.org/10.1016/j.cmet.2019.05.015] [PMID: 31204283]
[83]
Ludwig N, Whiteside TL, Reichert TE. Challenges in exosome isolation and analysis in health and disease. Int J Mol Sci 2019; 20(19): 4684.
[http://dx.doi.org/10.3390/ijms20194684] [PMID: 31546622]
[84]
Hollands P, Aboyeji DR, Ovokaitys T. The action of modulated laser light on human very small embryonic-like (hVSEL) stem cells in Platelet Rich Plasma (PRP). Cell R 2020; 4(8): e2990.
[85]
Ratajczak MZ, Ratajczak J, Suszynska M, Miller DM, Kucia M, Shin DM. A novel view of the adult stem cell compartment from the perspective of a quiescent population of very small embryonic-like stem cells. Circ Res 2017; 120(1): 166-78.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.309362] [PMID: 28057792]
[86]
Guerin CL, Blandinières A, Planquette B, et al. Very small embryonic-like stem cells are mobilized in human peripheral blood during hypoxemic COPD exacerbations and pulmonary hypertension. Stem Cell Rev 2017; 13(4): 561-6.
[http://dx.doi.org/10.1007/s12015-017-9732-6] [PMID: 28285391]
[87]
Marlicz W, Zuba-Surma E, Kucia M, Blogowski W, Starzynska T, Ratajczak MZ. Various types of stem cells, including a population of very small embryonic-like stem cells, are mobilized into peripheral blood in patients with Crohnʼs disease. Inflamm Bowel Dis 2012; 18(9): 1711-22.
[http://dx.doi.org/10.1002/ibd.22875] [PMID: 22238186]
[88]
Zuba-Surma EK, Wojakowski W, Ratajczak MZ, Dawn B. Very small embryonic-like stem cells: Biology and therapeutic potential for heart repair. Antioxid Redox Signal 2011; 15(7): 1821-34.
[http://dx.doi.org/10.1089/ars.2010.3817] [PMID: 21194389]
[89]
Brindley J. A theoretical mechanism for the action of songmodulated laser light on human very small embryonic-like (hVSEL) stem cells in platelet rich plasma (PRP). CellR4 9 2021; e3201.
[90]
Ovokaitys T. Intravenous SONG-modulated laser-activated allogeneic cord blood mesenchymal stem cells for the treatment of endstage heart failure: a preliminary clinical study. CellR4 9 2021; 2021: e3280.
[91]
Zuba-Surma EK, Wu W, Ratajczak J, Kucia M, Ratajczak MZ. Very small embryonic-like stem cells in adult tissues—Potential implications for aging. Mech Ageing Dev 2009; 130(1-2): 58-66.
[http://dx.doi.org/10.1016/j.mad.2008.02.003] [PMID: 18377952]
[92]
Ratajczak MZ, Liu R, Ratajczak J, Kucia M, Shin DM. The role of pluripotent embryonic-like stem cells residing in adult tissues in regeneration and longevity. Differentiation 2011; 81(3): 153-61.
[http://dx.doi.org/10.1016/j.diff.2011.01.006] [PMID: 21339038]
[93]
Galkowski D, Ratajczak MZ, Kocki J, Darzynkiewicz Z. Of cytometry, stem cells and fountain of youth. Stem Cell Rev 2017; 13(4): 465-81.
[http://dx.doi.org/10.1007/s12015-017-9733-5] [PMID: 28364326]
[94]
Zhang W, Qu J, Liu GH, Belmonte JCI. The ageing epigenome and its rejuvenation. Nat Rev Mol Cell Biol 2020; 21(3): 137-50.
[http://dx.doi.org/10.1038/s41580-019-0204-5] [PMID: 32020082]
[95]
Topart C, Werner E, Arimondo PB. Wandering along the epigenetic timeline. Clin Epigenetics 2020; 12(1): 97.
[http://dx.doi.org/10.1186/s13148-020-00893-7] [PMID: 32616071]
[96]
Marešová P, Mohelská H, Dolejš J, Kuča K. Socio-economic aspects of Alzheimer’s disease. Curr Alzheimer Res 2015; 12(9): 903-11.
[http://dx.doi.org/10.2174/156720501209151019111448] [PMID: 26510983]
[97]
Braga DL, Mousovich-Neto F, Tonon-da-Silva G, Salgueiro WG, Mori MA. Epigenetic changes during ageing and their underlying mechanisms. Biogerontology 2020; 21(4): 423-43.
[http://dx.doi.org/10.1007/s10522-020-09874-y] [PMID: 32356238]
[98]
Asadi Shahmirzadi A, Edgar D, Liao CY, et al. Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice. Cell Metab 2020; 32(3): 447-456.e6.
[http://dx.doi.org/10.1016/j.cmet.2020.08.004] [PMID: 32877690]
[99]
Bhullar KS, Hubbard BP. Lifespan and healthspan extension by resveratrol. Biochim Biophys Acta Mol Basis Dis 2015; 1852(6): 1209-18.
[http://dx.doi.org/10.1016/j.bbadis.2015.01.012] [PMID: 25640851]
[100]
Ros M, Carrascosa JM. Current nutritional and pharmacological anti-aging interventions. Biochim Biophys Acta Mol Basis Dis 2020; 1866(3): 165612.
[http://dx.doi.org/10.1016/j.bbadis.2019.165612] [PMID: 31816437]
[101]
Piskovatska V, Storey KB, Vaiserman AM, Lushchak O. The use of metformin to increase the human healthspan. Adv Exp Med Biol 2020; 1260: 319-32.
[http://dx.doi.org/10.1007/978-3-030-42667-5_13] [PMID: 32304040]
[102]
Bin-Jumah MN, Nadeem MS, Gilani SJ, et al. Genes and longevity of lifespan. Int J Mol Sci 2022; 23(3): 1499.
[http://dx.doi.org/10.3390/ijms23031499] [PMID: 35163422]