Siwen Cui
ABSTRACT
Aging is the process of progressive cellular senescence and tissue degeneration that eventually leads to organismal death. This degeneration manifests itself in the forms of various age-related diseases, such as neurodegenerative disorders, diabetes, and chronic inflammation. Although initially believed to be the inevitable final fate of human life, mounting evidence demonstrate the possibility to extend lifespan and decelerate the process of aging. From these observations, the question of whether aging can be reversed through cellular rejuvenation inspires further research. In humans, germline cells activate a natural program of rejuvenation in fertilization events, suggesting the possibility of cellular age reversal. While the nuance of the underlying mechanism is unclear, reprogramming the epigenome during aging seems to play central role.This project aims to identify candidate age reprogramming genes as alternatives to OSKM through directly comparing senescent and young cells (with gene expression data from human bone marrow-derived stromal cells, mouse retinal ganglion cells, and mouse fibroblasts).
- Ferrell JE, Jr. Bistability, bifurcations, and Waddington's epigenetic landscape. Curr Biol. 2012;22(11):R458-66.Google Scholar
- Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663-76.Google Scholar
- Ocampo A, Reddy P, Martinez-Redondo P, Platero-Luengo A, Hatanaka F, Hishida T, In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming. Cell. 2016;167(7):1719-33 e12.Google Scholar
- Lu Y, Brommer B, Tian X, Krishnan A, Meer M, Wang C, Reprogramming to recover youthful epigenetic information and restore vision. Nature. 2020;588(7836):124-9.Google Scholar
- Mahmoudi S, Mancini E, Xu L, Moore A, Jahanbani F, Hebestreit K, Heterogeneity in old fibroblasts is linked to variability in reprogramming and wound healing. Nature. 2019;574(7779):553-8.Google Scholar
- Sarkar TJ, Quarta M, Mukherjee S, Colville A, Paine P, Doan L, Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in human cells. Nat Commun. 2020;11(1):1545.Google Scholar
- Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-217.Google Scholar
- Soria-Valles C, Lopez-Otin C. iPSCs: On the Road to Reprogramming Aging. Trends Mol Med. 2016;22(8):713-24.Google Scholar
- Adler AS, Sinha S, Kawahara TL, Zhang JY, Segal E, Chang HY. Motif module map reveals enforcement of aging by continual NF-kappaB activity. Genes Dev. 2007;21(24):3244-57.Google Scholar
- Luscher TF, Barton M. Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs. Circulation. 2000;102(19):2434-40.Google ScholarCross Ref
- Rosano L, Spinella F, Bagnato A. Endothelin 1 in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2013;13(9):637-51.Google Scholar
- Ihara M, Noguchi K, Saeki T, Fukuroda T, Tsuchida S, Kimura S, Biological profiles of highly potent novel endothelin antagonists selective for the ETA receptor. Life Sci. 1992;50(4):247-55.Google Scholar
- Yeager ME, Belchenko DD, Nguyen CM, Colvin KL, Ivy DD, Stenmark KR. Endothelin-1, the unfolded protein response, and persistent inflammation: role of pulmonary artery smooth muscle cells. Am J Respir Cell Mol Biol. 2012;46(1):14-22.Google Scholar
- Scalera F, Dittrich R, Beckmann MW, Beinder E. Effect of endothelin-1 on intracellular glutathione and lipid peroxide availability and on the secretion of vasoactive substances by human umbilical vein endothelial cells. Eur J Clin Invest. 2002;32(8):556-62.Google Scholar
- Dong F, Zhang X, Wold LE, Ren Q, Zhang Z, Ren J. Endothelin-1 enhances oxidative stress, cell proliferation and reduces apoptosis in human umbilical vein endothelial cells: role of ETB receptor, NADPH oxidase and caveolin-1. Br J Pharmacol. 2005;145(3):323-33.Google Scholar
- Singh PB, Newman AG. Age reprogramming and epigenetic rejuvenation. Epigenetics Chromatin. 2018;11(1):73.Google Scholar
- Kerepesi C, Zhang B, Lee SG, Trapp A, Gladyshev VN. Epigenetic clocks reveal a rejuvenation event during embryogenesis followed by aging. Sci Adv. 2021;7(26).Google Scholar
- Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14(10):R115.Google Scholar
- Sanese P, Forte G, Disciglio V, Grossi V, Simone C. FOXO3 on the Road to Longevity: Lessons From SNPs and Chromatin Hubs. Comput Struct Biotechnol J. 2019;17:737-45.Google Scholar
- Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014;69 Suppl 1:S4-9.Google Scholar
- Maguire JJ, Davenport AP. Endothelin receptors and their antagonists. Semin Nephrol. 2015;35(2):125-36.Google Scholar
- Ihara M, Ishikawa K, Fukuroda T, Saeki T, Funabashi K, Fukami T, In vitro biological profile of a highly potent novel endothelin (ET) antagonist BQ-123 selective for the ETA receptor. J Cardiovasc Pharmacol. 1992;20 Suppl 12:S11-4.Google Scholar
- Ford RL, Mains IM, Hilton EJ, Reeves ST, Stroud RE, Crawford FA, Jr., Endothelin-A receptor inhibition after cardiopulmonary bypass: cytokines and receptor activation. Ann Thorac Surg. 2008;86(5):1576-83.Google Scholar
- Chen Y, Hanaoka M, Droma Y, Chen P, Voelkel NF, Kubo K. Endothelin-1 receptor antagonists prevent the development of pulmonary emphysema in rats. Eur Respir J. 2010;35(4):904-12.Google Scholar
- Xu H, Lin L, Yuan WJ. Antiarrhythmic effect of endothelin-A receptor antagonist on acute ischemic arrhythmia in isolated rat heart. Acta Pharmacol Sin. 2003;24(1):37-44.Google Scholar
- Ishikawa K, Ihara M, Noguchi K, Mase T, Mino N, Saeki T, Biochemical and pharmacological profile of a potent and selective endothelin B-receptor antagonist, BQ-788. Proc Natl Acad Sci U S A. 1994;91(11):4892-6.Google Scholar
- Tonari M, Kurimoto T, Horie T, Sugiyama T, Ikeda T, Oku H. Blocking endothelin-B receptors rescues retinal ganglion cells from optic nerve injury through suppression of neuroinflammation. Invest Ophthalmol Vis Sci. 2012;53(7):3490-500.Google Scholar
- Piechota-Polanczyk A, Kleniewska P, Goraca A. The influence of ETA and ETB receptor blockers on LPS-induced oxidative stress and NF-kappaB signaling pathway in heart. Gen Physiol Biophys. 2012;31(3):271-8.Google Scholar
- Chen CH, Cheng TH, Lin H, Shih NL, Chen YL, Chen YS, Reactive oxygen species generation is involved in epidermal growth factor receptor transactivation through the transient oxidization of Src homology 2-containing tyrosine phosphatase in endothelin-1 signaling pathway in rat cardiac fibroblasts. Mol Pharmacol. 2006;69(4):1347-55.Google Scholar
- Aliper AM, Csoka AB, Buzdin A, Jetka T, Roumiantsev S, Moskalev A, Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells. Aging (Albany NY). 2015;7(1):26-37.Google Scholar
- Ratajczak J, Shin DM, Wan W, Liu R, Masternak MM, Piotrowska K, Higher number of stem cells in the bone marrow of circulating low Igf-1 level Laron dwarf mice–novel view on Igf-1, stem cells and aging. Leukemia. 2011;25(4):729-33.Google Scholar
- Aldini G, Altomare A, Baron G, Vistoli G, Carini M, Borsani L, N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why. Free Radic Res. 2018;52(7):751-62.Google Scholar
- Kumar P, Liu C, Hsu JW, Chacko S, Minard C, Jahoor F, Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial. Clin Transl Med. 2021;11(3):e372.Google Scholar
- Kumar P, Osahon OW, Sekhar RV. GlyNAC (Glycine and N-Acetylcysteine) Supplementation in Mice Increases Length of Life by Correcting Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Abnormalities in Mitophagy and Nutrient Sensing, and Genomic Damage. Nutrients. 2022;14(5).Google Scholar
Index Terms
- Research on Cell Aging Based on Reprogramming Senescent Cells by Inhibiting Pro-Inflammatory TNF/Edn1 Pathway as a Potential Treatment of Age-Related Diseases
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