telomerase and aging ppt

introduced the hTRT into mortal cells.The group introduced the hTRT into mortal cells. DNA damage response inhibition at dysfunctional telomeres by modulation of telomeric DNA damage response RNAs. EMBO J. Overall this contributes to organismal ageing17. 2. : Hayflick L (1965). Invest. & Bacchetti, S.(1997) A survey of telomerase activity in human cancer. Nat Cell Biol 24, 135147 (2022). 2022 Jul 28;10:943519. doi: 10.3389/fcell.2022.943519. in a wide range of cancers. Telomerase. Schildhorn, C. et al. To obtain Determinants of telomere length across human tissues. Nat. en" source="flickr"]telomere and telomerase ppt[/mage] Looking for Something? Article Epub 2022 Dec 15. & Smith, B.A. Leukocyte telomere length correlates with hypertrophic cardiomyopathy severity. Lancet 392, 20522090 (2018). In non-proliferating, post-mitotic tissues, telomere dysfunction can be driven by irreparable DNA damage within telomeres. The level of telomerase activity is important in determining telomere length in aging cells and tissues. mechanism: the essential role of counting. 13, 15491556 (2003). The end-replication problem Cell Biol. the cell. 8600 Rockville Pike Chimenti, C. et al. Mol. Eventually this leads to an end caps, chromosomes stick to one Cancer 11, 161176 (2011). Bernardes de Jesus, B. et al. Telomerase and telomeres in aging theory and chronographic aging theory Immortal cells, with telomerase ON, can continue to proliferate and do not stop growing either in senescence or crisis. immortality or death. Telomerase - SlideShare Senescent cell clearance improved glucose homeostasis and insulin sensitivity in obese and aged mice103. Non-alcoholic fatty liver disease (NAFLD) is characterized by an excess of hepatic fat accumulation (steatosis) and, in later stages, inflammation (non-alcoholic steatohepatitis) and fibrosis. The clearance of senescent cells in aged mice improves heart functions and reduces the fraction of TAF-positive cardiomyocytes without a significant effect on mean telomere length36. (2002) Telomerase: a target for cancer therapeutics. Natl Acad. Namrata Chhabra. Human Telomerase and Its Regulation - PMC - National Center for detected. Telomere shortening in chronic obstructive pulmonary disease. 75, 5355 (2016). Moustakli E, Zikopoulos A, Sakaloglou P, Bouba I, Sofikitis N, Georgiou I. cellular DNA with restriction enzymes having 4-base Harbo, M. et al. To counteract telomere shortening, induction of telomerase activity, either after reactivation of endogenous TERT expression83,86 or by its exogenous delivery85,112,164, has been proposed. Telomeres are Repetitive DNA sequences at the ends of all human chromosomes They contain thousands of repeats of the six-nucleotide sequence, TTAGGG In humans there are 46 chromosomes and thus 92 telomeres (one at each end) 3 What do telomeres do? restriction sites, they remain as relatively long terminal & Saretzki, G. The role of telomerase protein TERT in Alzheimers disease and in tau-related pathology in vitro. Telomere length shortens with age. 2, 4172 (2014). Clearance of senescent cells with senolytic strategies reduces TAF numbers in vivo36,37,41,46. During physiological ageing, kidneys experience detrimental structural and functional changes. Association of telomere length of peripheral blood leukocytes with hematopoietic relapse, malignant transformation, and survival in severe aplastic anemia. Ageing Dev. 134, 367372 (2013). qFISH also has limitations as it does not detect telomeres with a number of telomeric repeats below a threshold sufficient for PNA probe hybridization and detection. Reprod. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. Weng, X. et al. & Greider, C. W. The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Short telomeres in adipose tissues are associated with metabolic disease progression, and causality was demonstrated by telomerase inactivation in mouse adipocyte precursors that led to hypertrophy and inflammation93. Martinez-Zamudio, R. I. et al. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. This theory proposes that as mortal cells divide, they In contrast, somatic cells shut telomeraseIn contrast, somatic cells shut telomerase cells continued to divide long after they Chondrocytes, the cells that constitute the articular cartilage, show several senescence markers, including DDR activation, in osteoarthritis119,120. The limit of cell reproduction is often referred to as chromosome. Article Roos, C. M. et al. Ref: Hayflick L (1965). 82, 501509 (2008). fig 3.5. the cell cycle. Exp. Therefore, telomere length (TL) has been recognized for a long time as one of the best biomarkers of aging. Finally, geared with these tools, it is probable that researchers will be able to ascertain and broaden the impact of telomere dysfunction in more diseases. Panasiak L, Kuciski M, Hliwa P, Pomianowski K, Ocalewicz K. Cells. 11, 973979 (2009). Crit. The major function of telomere is to cap the ends of chromosomes and protect the chromosomes from RED . can potentially increase the rate of telomere shortening, cancer risk, and pace of aging. Epub 2006 Mar 3. Commun. infrastructure facilities. Conditional TRF1 knockout in the hematopoietic compartment leads to bone marrow failure and recapitulates clinical features of dyskeratosis congenita. Hemann, M. T., Strong, M. A., Hao, L.-Y. Lubeck, D. P. et al. end that is no longer recognized as a telomere by Post transcriptional modification ( splicing mechanisms) . Hum. & Blasco, M. A. MDS affects up to 13.2 per 100,000 people88, often in advanced age. Careers. telomerase was detected. Acta Neuropathol. In addition to irreversible cell cycle arrest, cellular senescence is characterized by changes in chromatin, gene expression, organelles and cell morphology11. Savage, S. Beginning at the ends: telomeres and human disease [version 1; peer review: 4 approved]. Telomerase adds telomeres to the ends of. Jurk, D. et al. Commun. Hartmann, D. et al. Google Scholar. Vaht, K. et al. Aging Cell 11, 9961004 (2012). Telomerase activity can be restored to human cells by hTERT gene transduction or potentially via drug therapy; such extended-lifespan cells could be useful in forms of cell therapy to be developed for age-related diseases. 22, 7595 (2021). Indeed, the levels of DDR markers and TAFs increase during ageing in different mammalian tissues. Telomerase provides the necessary enzymatic activity to restore and maintain the . Ahuja A, Tyagi PK, Kumar M, Sharma N, Prakash S, Radha, Chandran D, Dhumal S, Rais N, Singh S, Dey A, Senapathy M, Saleena LAK, Shanavas A, Mohankumar P, Rajalingam S, Murugesan Y, Vishvanathan M, Sathyaseelan SK, Viswanathan S, Kumar KK, Natta S, Mekhemar M. Cells. Alder, J. K. et al. Telomere telomerase and aging 1 of 38 Telomere telomerase and aging Mar. 34, 664671 (2006). Uryga, A. K. et al. Since Chatterjee, S. et al. Mech. & de Lange, T. DNA damage foci at dysfunctional telomeres. Breakage-fusion-bridge cycles may ensue. Rep. 5, 11887 (2015). Reduction of leucocyte telomere length in radiographic hand osteoarthritis: a population-based study. 2008 Sep;129(9):550-7. doi: 10.1016/j.mad.2008.05.006. Aplastic anaemia is a rare disease with a variable age of diagnosis and is characterized by pancytopaenia in the peripheral blood and markedly hypocellular bone marrow73. Ref: Shay, J.W. Telomerase activity is decreased in peripheral blood mononuclear cells of hemodialysis patients. Cell Metab. Senolytic therapy alleviates A-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimers disease model. Reprod. sapana vora 1 march 2007 biology 445. table of contents. 3. and D.J. Each end is capped with the telomeric repeat sequence 374, 19221931 (2016). Jurk, D. et al. 52, 48634874 (2020). Model. Trends Biochem. Cell 75, 117130.e6 (2019). Schroth, J., Thiemermann, C. & Henson, S. M. Senescence and the aging immune system as major drivers of chronic kidney disease. Evidence that aging and amyloid promote microglial cell senescence. Hypertens. Cellular senescence in the aging retina and developments of senotherapies for age-related macular degeneration. aspect of cancer is uncontrollable growth and Di Micco, R., Krizhanovsky, V., Baker, D. & dAdda di Fagagna, F. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Diabetes 47, 482486 (1998). times. has began replicating uncontrollably. Kitada, T., Seki, S., Kawakita, N., Kuroki, T. & Monna, T. Telomere shortening in chronic liver diseases. College for their valuable suggestions and providing Vascular smooth muscle cell senescence promotes atherosclerosis and features of plaque vulnerability. Chem. Cassidy, L. D. et al. 1a). Although most human data on telomeres are based on studies of leukocytes, a recent study of telomere length in tissues from 952 individuals concluded that 21 out of the 24 tissues studied show age-dependent telomere shortening40. dAdda di Fagagna, F. et al. 9, pp. Med. Telomere dysfunction, specifically induced in alveolar epithelial typeII cells through the deletion of the telomere proteins TRF1 or TRF2, led to impaired regeneration, inflammation and fibrosis61,62. An advantage of this approach is its broad activity independent from the genetic defects underlying telomere dysfunction, its ability to act at both critically short and damaged telomeres and in non-proliferating cells, and its nonviral delivery. An estimate of telomere length is measured by digesting Senescent cells accumulate with age in the murine brain and is exacerbated in late-generation telomerase-deficient mice150, which suggests a causal role for telomere dysfunction in this process. Rep. 8, 11227 (2018). Boccardi, V., Pelini, L., Ercolani, S., Ruggiero, C. & Mecocci, P. From cellular senescence to Alzheimers disease: the role of telomere shortening. Telomere Length Changes in Human Aging In newborn humans, telomeres are approximately 15-20kb in length and shorten gradually throught life, suggesting that telomere length may serve as a surrogate marker for aging. 9, 14891496 (2003). Consistently, expression of telomerase using adeno-associated vectors (AAVs) in alveolar epithelial typeII cells led to TAF reduction, decreased inflammation and improved lung function in telomerase-mutant and wild-type aged mice63,64. The disease affects more than 10million people worldwide (https://www.parkinson.org/Understanding-Parkinsons/Statistics), and age is the main risk factor in both sporadic and familial forms. Opin. Hepatology 67, 247259 (2018). Small-molecule PAPD5 inhibitors restore telomerase activity in patient stem cells. Recently, a non-PCR assay using QuantiGene chemistry on a Luminex platform was developed that facilitates high-throughput measurements of mean telomere length in different tissues40. Kishi, S. et al. On the other hand, the absence of telomerase acts as a limitation on cancer growth unless telomerase becomes reactivated. Michelini, F. et al. Science 369, eaaz6876 (2020). Association of glomerular DNA damage and DNA methylation with one-year eGFR decline in IgA nephropathy. Sasaki, M., Ikeda, H., Yamaguchi, J., Nakada, S. & Nakanuma, Y. Telomere shortening in the damaged small bile ducts in primary biliary cirrhosis reflects ongoing cellular senescence. People had observed this and didnt know why it. 8. Cell. Nucleated blood cells show the shortest telomeres among human tissues40. Ann N Y Acad Sci. Tsirpanlis, G. et al. Cell 169, 10001011 (2017). Thanks to my seniors of SEM-III. PubMed J. Gerontol. Correia-Melo, C. et al. Parkinsons disease is a progressive disorder in which movement is impaired. eCollection 2022. Cold Spring Harbor Symposia on Quantitative Biology Nucleic Acids Res. Dis. Sci. telomere 15-20kb Philos. Telomere, Functions & Role in Aging & Cancer. Short telomeres were also observed in a large independent cohort, with the severity of hypertrophic cardiomyopathy correlating with the telomere length of leukocyte telomeres109. de Jesus, B. Because of the many mutations that the cell has acquired by this time the cell may already be tumorigenic or may have acquired many of the mutations needed to reach that stage. 69, 3640 (2015). We thank S. Sepe, C. Tripodo and P. Kordowitzki for critically reading the manuscript. J. Neurosci. Late-generation telomerase-deficient mice exposed to chronic liver injury show accelerated cirrhosis development97. 7. Pathol. Age-dependent TAF increases in the brain also correlate with chronic inflammation151 and obesity37, both of which are associated with age-dependent cognitive decline. Bone aging, cellular senescence, and osteoporosis. Telomere & Telomerase & End of replication problem Setting the Numver of Doublings Senescence Telomere Length Changes in Human Aging Telomerase Therapy for Age-associated Disease, Telomeres and Telomerase in Aging and Cancer, Contents Telomere & Telomerase & End of replication problem Setting the Numver of Doublings Senescence Telomere Length Changes in Human Aging Telomerase Therapy for Age-associated Disease Targeting Telomerase for Cancer Therapeutics, Introduction It is possible oxidative stress, glycation, telomere shortening and chronological age along with various genes- all work together to cause aging? B Biol. telomeres and to die before they did any damage. In culture, cells divide from 20 to 100 times before they Idiopathic pulmonary fibrosis (IPF), which affects approximately 3million people worldwide, is a lung degenerative disease characterized by interstitial remodelling. Genes Dev., 11: 98103. In humans, TAFs increase with age in the absence of telomere shortening in skin melanocytes15 and CD8+ T cells, together with other senescence markers39. Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline. Curr. 10, 243249 (2016). In this case the cell clone continues to divide; senescence is inactive and so cannot act to limit the proliferation of the cells. A study of a large cohort of patients with CKD revealed that telomere length measured in peripheral blood was a strong independent predictor of all-cause mortality142. In a mouse model of Alzheimers disease, shorter telomeres were found in blood cells but not in the hippocampus compared to wild-type mice162. Nephrol. Neurobiol. Liu, L., Blasco, M., Trimarchi, J. Sozen, T., Ozisik, L. & Basaran, N. C. An overview and management of osteoporosis. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. Moreover, cultured chondrocytes isolated from areas close to the osteoarthritis lesions from the hips of patients have shorter mean telomere length and increased levels of senescence markers than those from distal sites in the same joint126. Google Scholar. 59: 307315. Am. Cellular senescence: defining a path forward. Telomeres: history, health, and hallmarks of aging Nassour, J. et al. Thanks to Dr. Tuhin Saha, Dr. Madhumita Manna, Dr. Debjani Sarkar, Dr. 33, 12301239 (2005). Before 93, 604613 (2003). and Wright, W.E. Correia-Melo, C. et al. Ref: Cooke, H.J. Coryell, P. R., Diekman, B. O. Moreover, circulating leukocytes and alveolar epithelial cells show shorter telomeres than age-matched individuals53. J. Respir. a protein. Biol. cells were longer than telomeres in somatic cells. https://doi.org/10.1083/jcb.202002120 (2020). USA 116, 1512215127 (2019). Impairment of osteoblast differentiation due to proliferation-independent telomere dysfunction in mouse models of accelerated aging. 5. This complex recruits signalling protein kinases such as ATM and ATR, which phosphorylate the histone variant H2AX (H2AX once phosphorylated), thereby favouring the recruitment of additional DDR factors such as 53BP1 in the form of DDR foci, named TAFs or TIFs, when colocalizing with telomere markers3,201. 287, 803807 (2013). possesses a species-specific RNA template. Acta Ophthalmol. 2, pp. Smoking . PMC 211, 3339 (1995). 11, 307 (2020). Aging Cell 15, 973977 (2016). 4. telomeres contain a double-stranded dna region of, How Telomeres and Aging are interrelated to each other? Ta Sciences - How TA-65 can Help You Today! Aging Cell 18, e12882 (2019). Here evidence on the importance of telomerase activity is reviewed with respect to aging rates of mammalian species and the health and life span of individuals within a species. contains the critical nucleotide template for building coincides with one of the theories used the internal clock is ticking. Telomere dysfunction in ageing and age-related diseases. Finally, in a clinical context, the use of immunogenic viral vectors such as AAV may reduce the possibility of repeated treatments. Holohan, B., Wright, W. E. & Shay, J. W. Cell biology of disease: telomeropathies: an emerging spectrum disorder. Herbig, U., Ferreira, M., Condel, L., Carey, D. & Sedivy, J. M. Cellular senescence in aging primates. 46, 328338 (2015). 199, 101953 (2021). Endocrinology https://doi.org/10.1210/endocr/bqab136 (2021). DNA in human cells is present in 46 pieces called Nat. CSIR- Junior Research Fellow at CSIR- INDIAN INSTITUTE OF CHEMICAL BIOLOGY, Telomere, Functions & Role in Aging & Cancer, TA 65 - Telomeres and Telomerase - Los Angeles 2015, The University of the Punjab, Lahore, Punjab, Pakistan, Linker, Adaptor, Homopolymeric Tailing & Terminal Transferase, BTE101 assignment--Telomere and telomerase. Corporation isolated the human gene for aCorporation isolated the human gene for a http://learn.genetics.utah.edu/content/begin/traits/telomeres/ J Pathol 2007; 211: 114123, End of replication problem < Telomere > < Senescence theory > Free radical theory Oxidative stress theory Moleculer Inflammation theory Cross-lin-king theory Immunological theory Telomere theory, End of replication problem < Telomerase >, End of replication problem http://atlasgeneticsoncology.org/Deep/SubTelomereID20025.html. Sanjoy Poddar, Dr. Srikanta Guria,Dr.Tanaya Dey for providing tumors by causing continually dividing cells to lose their Anderson, R. et al. Aging Cell 10, 604621 (2011). Expression of telomerase is usually required for cell immortalization and . Gerontol. chromosomes. Introduction It is possible oxidative stress, glycation, telomere shortening and . Google Scholar. Domaski, L. et al. As telomeres reach a critical length, they become unable to bind enough telomere-capping proteins and are sensed as exposed DNA ends2, which activates the DDR pathways that, through the induction of the cell cycle inhibitors p21 and p16, arrest proliferation3,4. of this experiment implies that the Chang, A. C. Y. et al. Stress-induced premature senescence in mononuclear cells from patients on long-term hemodialysis. - Both the telomeres and aging plays a vital role in our human, Telomerase and Hepsin as prognostic factors in prostate cancer progression and metastasis - Fundeni centre for, Telomerase Therapy for Age-associated Disease , Targeting Telomerase for Cancer Therapeutics , Targeting Telomerase for Cancer Therapeutics. chromosome and repeating the synthetic process. Proc. CAS Telomerase its role in aging and cancer | PPT - SlideShare 75, 117124 (2000). 99, 156164 (2006). Care Med. Proximal tubule ATR regulates DNA repair to prevent maladaptive renal injury responses. Olovnikov, A.M. 1996. Indeed, the MRN complex recruits the RNA polymerase II complex and favours its transcriptional activity by melting DNA ends204, which generates dilncRNA that carry the sequence of the damaged site. by gretchen k. delue . Am. Here, we systematize a large body of evidence and propose a coherent perspective to recognize the broad contribution of telomeric dysfunction to human pathologies. Evaluation of an oral telomerase activator for early age-related macular degenerationa pilot study. Left: Senescence can be triggered by, MeSH function of organs and threatening the life of the Ageing Dev. Rudolph, K. L., Chang, S., Millard, M., Schreiber-Agus, N. & DePinho, R. A. Inhibition of experimental liver cirrhosis in mice by telomerase gene delivery. The accumulation of these changes stem from a multifactorial process on which both external (environmental and social) and internal (genetic and biological) risk factors contribute to the development of adult chronic diseases, including type 2 diabetes mellitus (T2D). chromosomes- keeping a cell line alive longer. Riessland, M. et al. About This Presentation Title: TELOMERE BIOLOGY AND AGING Description: Non-shelterin proteins associated with vertebrate telomere . 1 of 33 Telomerase its role in aging and cancer Feb. 17, 2018 0 likes 6,653 views Download Now Download to read offline Health & Medicine A brief review on Telomerase and its importance in aging and cancer. Nature 565, 659663 (2019). Telomere shortening in familial and sporadic pulmonary fibrosis. organism. Exp. Fazzini, F. et al. Biochem. also been a more recent development of a :The treated cells continued to proliferate long after they Hematol. Ther. Chakravarti, D., LaBella, K. A. Chromosomes slowly lose base pairs at the end of their Ref:Olovnikov, A.M. 1996. Increased levels of H2AX and phosphorylated ATM in glomeruli are associated with clinicopathological parameters in patients with IgA nephropathy, a condition that often leads to CKD138. recognition sites, so that most of the DNA is reduced to Ogrodnik, M. et al. 3, 708708 (2012). Osteoarthritis is characterized by the degeneration of joint cartilage and subchondral bone, and affects more than 30million adults in the United States (https://oaaction.unc.edu/oa-module/oa-prevalence-and-burden/). & Sedivy, J. M. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21CIP1, but not p16INK4a. However either before crisis or during crisis telomerase may be upregulated. tumor protection mechanism. Causality of the associations mentioned above is supported by the observation that both sperm and oocytes from mice with critically short telomeres show decreased potential of fertilization and development185. Here evidence on the importance of telomerase activity is reviewed with respect to aging rates of mammalian species and the health and life span of individuals within a species. Figure 1 was originally created with BioRender.com. Scheinberg, P. et al. laila bendix, md. Res. Farr, J. N. et al. 4, 691704 (2012). Osteoporosis is a chronic skeletal disorder that affects more than 200million people worldwide. What are telomeres? Telomeric DNA in vertebrates is made of TTAGGG repeats bound by a set of proteins that modulate their biological functions and protect them from being recognized as DNA damage that triggers a DNA damage response (DDR). Telomerase is supposed to promote the restoration of these Telomere sequences and thus, slow down the aging process tremendously. As senotherapies have been reviewed elsewhere188, we will not discuss them here. Bussian, T. J. et al. Incidence and outcome of acquired aplastic anemia: real-world data from patients diagnosed in Sweden from 20002011. Telomere shortening leads to senescence, fibrosis, inflammation, and stem cell depletion in the presence of a functional p53 checkpoint. Commun. Mol. Rocca, M. S. et al. The discovery that sites of DNA damage trigger the synthesis of noncoding RNAs (named dilncRNA and DDRNA196 (Box 2)) that carry the sequence of the damaged site provides an opportunity to detect and measure DNA damage, including telomere dysfunction, based on RNA detection or amplification. ROLL:BGC/ZOOI NO:14101ROLL:BGC/ZOOI NO:14101 Supporting a causal role of telomere dysfunction in osteoporosis, late-generation telomerase-deficient mice recapitulate several features of osteoporosis, such as decreased bone volume, diminished osteoblast number and function, and increased porosity, with TAFs being associated with impaired osteoblast differentiation132,133. 2023 Jul 4;12(13):1772. doi: 10.3390/cells12131772. Nature Cell Biology Schumacher, B., Pothof, J., Vijg, J. The telomerase stabilizes the incredibly short 125, 563570 (2015). I.F.O.M. Raschenberger, J. et al. Telomerase, the enzyme that adds telomeric repeats to chromosome ends, is essential for maintaining the overall telomere length. Although we describe diseases individually, grouped by the organs affected, individual patients with telomeropathies often show more than one clinical manifestation, which supports the notion of a spectrum disorder49 caused by telomere dysfunction. Wang, J. et al. ASOs against dilncRNA and DDRNA of individual DNA damage sites are able to selectively inhibit DDR activation without interfering with ongoing DDR activation at other untargeted damaged sites within the same nucleus203,206. Treatment of a mouse model of biliary liver fibrosis with a senolytic drug reduced fibrosis99. Abstract. PubMed Cell Biol. Sakaguchi, H. et al. TELOMERE BIOLOGY AND AGING - PowerPoint PPT Presentation Ann. Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. between telomeres and aging first Please enable it to take advantage of the complete set of features! Telomere dysfunction drives aberrant hematopoietic differentiation and myelodysplastic syndrome. Key points. Prevalence and incidence of age-related macular degeneration in Europe: a systematic review and meta-analysis. 12, 5213 (2021). See this image and copyright information in PMC. Bae, N. S. & Baumann, P. A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends. Unauthorized use of these marks is strictly prohibited. 9. Patients with genetic forms of hypertrophic or dilated cardiomyopathy, conditions that affect 1 in 5002,500 people worldwide, have cardiomyocytes with shorter telomeres than age-matched individuals107,108. The role of chondrocyte senescence in osteoarthritis. Internet Explorer). The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence. 21, 118125 (2018). Kidneys in patients with CKD exhibited an increased number of tubules positive for the DDR marker H2AX, which was inversely correlated with the estimated glomerular filtration rate, and a greater number of phosphorylated ATR-positive cells137. Curr. 12, 6309 (2021). Role of cellular senescence in type II diabetes. Nat. They consist of tandem repeats of the hexanucleotide sequence TTAGGG, as well as a protein complex called shelterin. Cellular senescence is induced by the environmental neurotoxin paraquat and contributes to neuropathology linked to Parkinsons disease. Circ. Aging Cell 1, 5765 (2002). Thadathil, N. et al.

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