Environmental stress, ageing and glial cell senescence: a novel mechanistic link to Parkinson's disease?
Open accessAbstract
Exposure to environmental toxins is associated with a variety of age-related diseases including cancer and neurodegeneration. For example, in Parkinson's disease (PD), chronic environmental exposure to certain toxins has been linked to the age-related development of neuropathology. Neuronal damage is believed to involve the induction of neuroinflammatory events as a consequence of glial cell activation. Cellular senescence is a potent anti-cancer mechanism that occurs in a number of proliferative cell types and causes the arrest of proliferation of cells at risk of malignant transformation following exposure to potentially oncogenic stimuli. With age, senescent cells accumulate and express a senescence-associated secretory phenotype (SASP; that is the robust secretion of many inflammatory cytokines, growth factors and proteases). Whereas cell senescence in peripheral tissues has been causally linked to a number of age-related pathologies, little is known about the induction of cellular senescence and the SASP in the brain. On the basis of recently reported findings, we propose that environmental stressors associated with PD may act in part by eliciting senescence and the SASP within non neuronal glial cells in the ageing brain, thus contributing to the characteristic decline in neuronal integrity that occurs in this disorder.
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Diseases associated with the accumulation of senescent cells, such as neurodegenerative disorders, osteoarthritis and idiopathic pulmonary fibrosis, exhibit iron dyshomeostasis, where iron burden often correlates with disease severity.
“Diseases associated with the accumulation of senescent cells, such as neurodegenerative disorders (e.g. Alzheimer's and Parkinson's) [20], [21], [22], osteoarthritis [23], [24] and idiopathic pulmonary fibrosis [25], also exhibit iron dyshomeostasis where often iron burden correlates with disease severity [14], [15], [26], [27], [28], [29], [30], [31], [32], [33], [34].”
From Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis (2018) · cites this paper as [22]
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Mansour, H., Chamberlain, C. G., Weible II, M. W., Hughes, S., Chu, Y., & Chan‐Ling, T. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2008.00402.x · Cited by 84 · see citing works
Molecular Insights into Parkinson's Disease
Rochet, J., Hay, B. A., & Guo, M. (2012) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-385883-2.00011-4 · Cited by 83 · see citing works
Recent advances in (patho)physiology of astroglia
Verkhratsky, A., & Parpura, V. (2010) · Acta Pharmacologica Sinica · doi:10.1038/aps.2010.108 · Cited by 82 · see citing works
Senescence of the retinal pigment epithelium.
Hjelmeland, L. M., Cristofolo, V. J., Funk, W., Rakoczy, E., & Katz, M. L. (1999) · PubMed · Cited by 82 · see citing works
Repeated Lipopolysaccharide Stimulation Induces Cellular Senescence in BV2 Cells
Yu, H.-M., Zhao, Y.-M., Luo, X.-G., Feng, Y., Ren, Y., Shang, H., He, Z.-Y., Luo, X.-M., Chen, S.-D., & Wang, X.-Y. (2012) · Neuroimmunomodulation · doi:10.1159/000330254 · Cited by 76 · cited 3× · see citing works
“Exposure to an oxidant (H202) or proteasome inhibitor, or replicative exhaustion all led to the development of characteristics of senescence, including growth arrest, an enlarged flattened morphology, SA-Bgal expression, increased expression of the cell-cycle inhibitors p21 and p16INK4a, and the development of senesce…”
InfluentialPeng, J., Stevenson, F. F., Oo, M. L., & Andersen, J. K. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.10.045 · Cited by 74 · see citing works
Sawada, M., Sawada, H., & Nagatsu, T. (2008) · Neurodegenerative Diseases · doi:10.1159/000113717 · Cited by 71 · cited 1× · see citing works
“There is strong evidence to suggest that, with advanced age, functional abnormalities occur in the microglia that impair their ability to respond efficiently to stimuli [73, 74].”
Hyperoxia‐induced premature senescence requires p53 and pRb, but not mitochondrial matrix ROS
Klimova, T. A., Bell, E. L., Shroff, E. H., Weinberg, F. D., Snyder, C. M., Dimri, G. P., Schumacker, P. T., Budinger, G. R. S., & Chandel, N. S. (2008) · The FASEB Journal · doi:10.1096/fj.08-114256 · Cited by 63 · cited 1× · see citing works
“Furthermore, oxidative stress can induce cellular senescence, principally by activating the p53 pathway [24, 31, 32].”
Molecular insights into Parkinson's disease
Thomas, B., & Beal, M. F. (2011) · F1000 Medicine Reports · doi:10.3410/m3-7 · Cited by 60 · cited 1× · see citing works
“Lewy bodies contain a variety of proteins, including ubiquitin and alpha-synuclein [2].”
ING1a expression increases during replicative senescence and induces a senescent phenotype
Soliman, M. A., Berardi, P., Pastyryeva, S., Bonnefin, P., Feng, X., Colina, A. R., Young, D., & Riabowol, K. T. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2008.00427.x · Cited by 56 · see citing works
Induction of senescence‐associated growth inhibitors in the tumor‐suppressive function of retinoids
Roninson, I. B., & Dokmanovic, M. (2002) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10320 · Cited by 44 · cited 1× · see citing works
“Many DNA-damaging chemotherapies as well as radiotherapy can, for example, induce senescence [23, 24].”
The Role of Microglial Cellular Senescence in the Aging and Alzheimer Diseased Brain
Flanary, B. (2005) · Rejuvenation Research · doi:10.1089/rej.2005.8.82 · Cited by 40 · cited 1× · see citing works
“A comparative study examining both young and old autopsied human brains demonstrated that, with age, microglia transform morphologically from ramified to hypertrophic and dystrophic forms characterized by loss of fine branches (deramification), formation of cytoplasmic spheroids, beading and fragmentation [75, 76].”
Zhang, G., Cheng, X., Zhou, W., & Zhang, Y. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.04.075 · Cited by 23 · see citing works
Ruby, T., & Monack, D. M. (2011) · F1000 Biology Reports · doi:10.3410/b3-1 · Cited by 20 · see citing works
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Cellular senescence: from physiology to pathology
Muñoz-Espín, D., & Serrano, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3823 · Cited by 2,818 · see citing works
The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates
Franceschi, C., Garagnani, P., Morsiani, C., Conte, M., Santoro, A., Grignolio, A., Monti, D., Capri, M., & Salvioli, S. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00061 · Cited by 945 · see citing works
Chinta, S. J., Woods, G., Demaria, M., Rane, A., Zou, Y., McQuade, A., Rajagopalan, S., Limbad, C., Madden, D. T., Campisi, J., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.092 · Cited by 530 · see citing works
“We report the contribution of a factor thought to contribute to aging in many tissues: cellular senescence (Campisi, 2013; Chinta et al., 2013, 2015; Salminen et al., 2011).”
Parkinson's Disease and the Environment
Ball, N., Teo, W., Chandra, S., & Chapman, J. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00218 · Cited by 481 · see citing works
“Industrialized countries have higher urbanization leading to environmental degradation and exposure to environmental toxins (31).”
BackgroundMasaldan, S., Clatworthy, S. A. S., Gamell, C., Meggyesy, P. M., Rigopoulos, A.-T., Haupt, S., Haupt, Y., Denoyer, D., Adlard, P. A., Bush, A. I., et al. (2018) · Redox Biology · doi:10.1016/j.redox.2017.08.015 · Cited by 452 · see citing works
Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity
Palmer, A. K., Tchkonia, T., LeBrasseur, N. K., Chini, E. N., Xu, M., & Kirkland, J. L. (2015) · Diabetes · doi:10.2337/db14-1820 · Cited by 423 · see citing works
“Neurons can adopt a senescence-like phenotype, including DNA damage foci and SA-bgal activity in dementia and other neurodegenerative diseases (70,71).”
BackgroundTranscriptome signature of cellular senescence
Casella, G., Munk, R., Kim, K. M., Piao, Y., De, S., Abdelmohsen, K., & Gorospe, M. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz555 · Cited by 359 · see citing works
Calabrese, V., Santoro, A., Monti, D., Crupi, R., Di Paola, R., Latteri, S., Cuzzocrea, S., Zappia, M., Giordano, J., Calabrese, E. J., et al. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.10.379 · Cited by 356 · see citing works
Cellular Senescence in Neurodegenerative Diseases
Martínez‐Cué, C., & Rueda, N. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00016 · Cited by 285 · see citing works
Astrocyte senescence: Evidence and significance
Cohen, J., & Torres, C. (2019) · Aging Cell · doi:10.1111/acel.12937 · Cited by 281 · see citing works
Parkinson’s disease as a result of aging
Rodriguez, M., Rodriguez‐Sabate, C., Morales, I., Sanchez, A., & Sabate, M. (2015) · Aging Cell · doi:10.1111/acel.12312 · Cited by 214 · see citing works
“) patterns which are characteristic of senescence, reducing their ability to protect neurons (Mansour et al., 2008; Chinta et al., 2013).”
BackgroundSingh, S. S., Nand, S., Birla, H., Zahra, W., Singh, S. P., & Singh, S. P. (2019) · Neurotoxicity Research · doi:10.1007/s12640-019-00147-2 · Cited by 215 · see citing works
Saha, S., Buttari, B., Profumo, E., Tucci, P., & Saso, L. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.787258 · Cited by 206 · see citing works
“With age, the failure of the astrocytic Nrf2-antioxidant axis response upon inflammation and oxidative stress significantly influences VM astrocyte-microglia-neuron interactions (Chinta et al., 2013; L’Episcopo et al., 2013; Silva-Palacios et al., 2018; Serapide et al., 2020).”
BackgroundRole of sphingolipids in senescence: implication in aging and age-related diseases
Trayssac, M., Hannun, Y. A., & Obeid, L. M. (2018) · Journal of Clinical Investigation · doi:10.1172/jci97949 · Cited by 210 · see citing works
The role of cellular senescence in ageing of the placenta
Cox, L. S., & Redman, C. (2017) · Placenta · doi:10.1016/j.placenta.2017.01.116 · Cited by 181 · see citing works
Marchetti, B., Tirolo, C., L’Episcopo, F., Caniglia, S., Testa, N., Smith, J. A., Pluchino, S., & Serapide, M. F. (2020) · Aging Cell · doi:10.1111/acel.13101 · Cited by 185 · see citing works
“A critical role of both central and peripheral inflammation has become evident, with a panel pro/anti-inflammatory cytokines regulating neurogenesis (Butovsky et al., 2006; Chinta et al., 2013; Ekdhal, Kokaia, & Lindvall, 2009; Jakubs et al., 2008; L'Episcopo et al., 2011a; Monje et al., 2003; Pluchino et al., 2008; S…”
BackgroundThe concept of alpha-synuclein as a prion-like protein: ten years after
Steiner, J. A., Quansah, E., & Brundin, P. (2018) · Cell and Tissue Research · doi:10.1007/s00441-018-2814-1 · Cited by 183 · see citing works
“The brain environment during aging is characterized by inflammation that involves non-neuronal, proliferating and circulating cells such as microglia, astrocytes and oligodendrocytes (reviewed in Chinta et al. 2013).”
Clinical strategies and animal models for developing senolytic agents
Kirkland, J. L., & Tchkonia, T. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2014.10.012 · Cited by 168 · see citing works
“, 2013)), 6) neurodegenerative diseases (Alzheimer's disease and “tau-opathies”, Parkinson's, “chemo brain” after, for example, cis-platinum, HIV dementia (Chinta et al., 2013; Golde et al., 2009; Kirkland, 2013a; Krull et al., 2013)), 7) bone disorders (osteoporosis, osteoarthritis, fracture non-union (Bajada et al.”
Global Sensory Impairment in Older Adults in the United States
Correia, C., Lopez, K. J., Wroblewski, K., Huisingh-Scheetz, M. J., Kern, D. W., Chen, R. C., Schumm, L. P., Dale, W., McClintock, M. K., & Pinto, J. M. (2016) · Journal of the American Geriatrics Society · doi:10.1111/jgs.13955 · Cited by 172 · see citing works
Oxidative stress, cellular senescence and ageing
Pole, A., Dimri, M., & Dimri, G. P. (2016) · AIMS molecular science · doi:10.3934/molsci.2016.3.300 · Cited by 158 · see citing works
Immunosenescence and inflammaging: Mechanisms and role in diseases
Ajoolabady, A., Praticò, D., Tang, D., Zhou, S., Franceschi, C., & Ren, J. T. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102540 · Cited by 160 · see citing works
Siracusa, R., Scuto, M. C., Fusco, R., Salinaro, A. T., Ontario, M. L., Crea, R., Paola, R. D., Cuzzocrea, S., & Calabrese, V. (2020) · Antioxidants · doi:10.3390/antiox9090824 · Cited by 147 · see citing works
“The brains of 5 mice for each group were fixed, cut and colored with hematoxylin and eosin (H&E, Bio-Optica, Milan, Italy) and subsequently the sections were analyzed using an optical microscope connected to an imaging system (AxioVision, Zeiss, Milan, Italy), as previously described [30,35].”
BackgroundMethodThe complex relationships between microglia, alpha-synuclein, and LRRK2 in Parkinson's disease
Schapansky, J., Nardozzi, J. D., & LaVoie, M. J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2014.09.049 · Cited by 132 · see citing works
“, 2009; Barnett and Brewer, 2011; Cuervo and Macian, 2014), which is the single greatest risk factor in idiopathic PD (Hindle, 2010; Collier et al., 2011; Chinta et al., 2013).”
BackgroundDiversity of astroglial responses across human neurodegenerative disorders and brain aging
Ferrer, I. (2017) · Brain Pathology · doi:10.1111/bpa.12538 · Cited by 123 · see citing works
Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson’s Disease
Sepe, S., Milanese, C., Gabriels, S., Derks, K., Payán‐Gómez, C., van IJcken, W. F. J., Rijksen, Y., Nigg, A. L., Moreno, S., Cerri, S., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.071 · Cited by 121 · see citing works
The emerging role of senescent cells in tissue homeostasis and pathophysiology
Tominaga, K. (2015) · Pathobiology of Aging & Age-related Diseases · doi:10.3402/pba.v5.27743 · Cited by 112 · see citing works
Changes in the Transcriptome of Human Astrocytes Accompanying Oxidative Stress-Induced Senescence
Crowe, E. P., Tuzer, F., Gregory, B. D., Donahue, G., Gosai, S. J., Cohen, J., Leung, Y. Y., Yetkin, E., Nativio, R., Wang, L.-S., et al. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00208 · Cited by 110 · see citing works
“The induction of senescence in astrocytes has been implicated in neurodegenerative disease (Bhat et al., 2012; Chinta et al., 2013) .”
BackgroundLinares, C., Culqui, D. R., Carmona, R., Ortíz, C., & Díaz, J. (2016) · Environmental Research · doi:10.1016/j.envres.2016.10.020 · Cited by 109 · see citing works
Evidence of neuroprotective effects of saffron and crocin in a Drosophila model of parkinsonism
Rao, S. V., ., M., Yenisetti, S. C., & Rajini, P. S. (2015) · NeuroToxicology · doi:10.1016/j.neuro.2015.12.010 · Cited by 104 · see citing works
“The majority of cases of PD appear to be sporadic, likely to be caused by a combination of genetic and environmental risk factors, the most apparent being increasing age (Chinta et al., 2013).”
BackgroundFate of microglia during HIV‐1 infection: From activation to senescence?
Chen, N. C., Partridge, A. T., Sell, C., Torres, C. A., & Martín‐García, J. (2016) · Glia · doi:10.1002/glia.23081 · Cited by 93 · see citing works
“More specifically, senescent phenotypes have been observed in various cell types residing in different tissues including bronchial cells, adipocytes and pancreatic b cells, as well as in astrocytes, and development of senescence in those cells has been shown to contribute to and/or to be associated with the onset of p…”
BackgroundHouck, A. L., Seddighi, S., & Driver, J. A. (2018) · Current Aging Science · doi:10.2174/1874609811666180223154436 · Cited by 93 · see citing works
Targeting cellular senescence in cancer and aging: roles of p53 and its isoforms
Beck, J. A., Turnquist, C., Horikawa, I., & Harris, C. C. (2020) · Carcinogenesis · doi:10.1093/carcin/bgaa071 · Cited by 94 · see citing works
“In patients with Parkinson’s disease, increased numbers of senescent astrocytes may contribute to neurodegeneration (111,112).”
BackgroundKip, E., & Parr‐Brownlie, L. C. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101618 · Cited by 88 · see citing works
“An additional potential cause of age-related brain inflammation is glial senescence (Chinta et al., 2013).”
Alpha-Synuclein Preformed Fibrils Induce Cellular Senescence in Parkinson’s Disease Models
Verma, D., Seo, B. A., Ghosh, A., Ma, S.-X., Hernandez-Quijada, K., Andersen, J. K., Ko, H. S., & Kim, Y. (2021) · Cells · doi:10.3390/cells10071694 · Cited by 85 · see citing works
“Therefore, it is plausible that neurodegeneration is, at least in part, mediated by additional mechanisms including the induction of cellular senescence [5,9,12].”
BackgroundTrias, E., Beilby, P. R., Kovacs, M., Ibarburu, S., Varela, V., Barreto-Núñez, R., Bradford, S. C., Beckman, J. S., & Barbeito, L. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00042 · Cited by 85 · see citing works
Das, M. M., & Svendsen, C. N. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.09.020 · Cited by 76 · see citing works
Śmieszek, A., Stręk, Z., Kornicka, K., Grzesiak, J., Weiss, C., & Marycz, K. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040872 · Cited by 77 · see citing works
“Moreover, the increased risk of cognitive impairment in diabetes is also associated with senescence in the brain, however—not only neurons, but also infiltrating or glial cells [21].”
BackgroundCellular senescence: a view throughout organismal life
von Kobbe, C. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2879-8 · Cited by 69 · see citing works
mRNA methylation in cell senescence
Casella, G., Tsitsipatis, D., Abdelmohsen, K., & Gorospe, M. (2019) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1547 · Cited by 69 · see citing works
“…pulmonary disease, age-related chronic inflammation, macular degeneration, and cancer (Aravinthan et al., 2013, 2015; Boccardi, Pelini, Ercolani, Ruggiero, & Mecocci, 2015; Campisi & Robert, 2014; Chinta et al., 2013; Dimri et al., 1995; Ito et al., 2014; Kumar, Seeger, & Voswinckel, 2014).”
Functional Role of Cellular Senescence in Biliary Injury
Meng, L., Quezada, M., Levine, P., Han, Y., McDaniel, K. M., Zhou, T., Lin, E. P.-Y., Glaser, S. S., Meng, F., Francis, H., et al. (2015) · American Journal Of Pathology · doi:10.1016/j.ajpath.2014.10.027 · Cited by 68 · see citing works
Heterogeneous astrocytes: Active players in CNS
Hu, X., Yuan, Y., Wang, D., & Su, Z. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.03.017 · Cited by 66 · see citing works
“Similar mutual modulation of astrocytes and microglia is also observed during aging, which induces age-related neuroinflammation and neuronal degeneration in the brain (Chinta et al. 2013; Salminen et al. 2011).”
Stress granules counteract senescence by sequestration of PAI‐1
Omer, A., Patel, D. M., Lian, X. J., Sadek, J., Marco, S. D., Pause, A., Gorospe, M., & Gallouzi, I. (2018) · EMBO Reports · doi:10.15252/embr.201744722 · Cited by 66 · see citing works
“However, unlike apoptotic or necrotic cells, which lead to complete cell collapse and rapid elimination, senescent cells resist cell death, maintain an active metabolism, and are able to persist and accumulate over an extended period of time [2,4,71,72].”
Carbonyl Stress in Aging Process: Role of Vitamins and Phytochemicals as Redox Regulators
Ergin, V. (2013) · Aging and Disease · doi:10.14336/ad.2013.0400276 · Cited by 59 · see citing works
Yu, C., Narasipura, S. D., Richards, M. H., Hu, X., Yamamoto, B., & Al‐Harthi, L. (2017) · Aging Cell · doi:10.1111/acel.12593 · Cited by 57 · see citing works
“Astrocyte senescence is implicated in human brain aging (Kang et al., 2015) and in neurodegenerative diseases such as Alzheimer’s (Bhat et al., 2012) and Parkinson’s disease (Chinta et al., 2013).”
BackgroundHossain, M. S., Abe, Y., Ali, F., Youssef, M., Honsho, M., Fujiki, Y., & Katafuchi, T. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.3941-15.2017 · Cited by 55 · see citing works
“It has been reported that inflammatory stimuli, stress, and aging activate NF- B in glial and neuronal cells, leading to neuroinflammation (O’Neill and Kaltschmidt, 1997; Mattson and Camandola, 2001; Chinta et al., 2013), which is known to be associated with neurodegenerative diseases including AD (Frank-Cannon et al.”
BackgroundMechanisms and consequences of aneuploidy and chromosome instability in the aging brain
Andriani, G. A., Vijg, J., & Montagna, C. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.03.007 · Cited by 55 · see citing works
“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Although aneuploidy seems to be linked to NDs, it is not clear yet how ploidy changes would occur in post-mitotic cells, such as neurons.”
BackgroundInfluentialKucherenko, M. M., & Shcherbata, H. R. (2018) · Journal of Cell Science · doi:10.1242/jcs.202002 · Cited by 55 · see citing works
“…regulatory factors that control the same signaling cascade; for example, upon starvation, miRNAs from the miR-310s complex target several components of the conserved cholesterol-dependent hedgehog signaling pathway, thereby governing a quick and robust dietary stress response (Cicek et al., 2016).”
BackgroundInfluentialLeggio, L., L'Episcopo, F., Magrì, A., Ulloa‐Navas, M. J., Paternò, G., Vivarelli, S., Bastos, C. A. P., Tirolo, C., Testa, N., Caniglia, S., et al. (2022) · Advanced Healthcare Materials · doi:10.1002/adhm.202201203 · Cited by 54 · see citing works
Brown, D., Tamás, A., Reglődi, D., & Tizabi, Y. (2014) · Neurotoxicity Research · doi:10.1007/s12640-014-9468-x · Cited by 51 · see citing works
“Several studies propose that targeting the inflammatory pathway could have therapeutic advantage in the treatment of PD (Wersinger and Sidhu, 2002; Barcia et al. 2003; Carta and Pisanu, 2013; Chinta et al. 2013).”
Nrf2/Wnt resilience orchestrates rejuvenation of glia-neuron dialogue in Parkinson's disease
Marchetti, B. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101664 · Cited by 49 · see citing works
“With age, the described failure of the astrocytic Nrf2-antioxidant axis response upon inflammation and oxidative stress dramatically impact in VM astrocyte-microglia-neuron interactions [64,65,74,101,292].”
The Potential Role of m6A RNA Methylation in the Aging Process and Aging-Associated Diseases
Sun, J., Cheng, B., Su, Y., Li, M., Ma, S., Zhang, Y., Zhang, A., Cai, S., Bao, Q., Wang, S., et al. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.869950 · Cited by 48 · see citing works
Inflammaging, cellular senescence, and cognitive aging after traumatic brain injury
Lu, Y., Jarrahi, A., Moore, N. D., Bartoli, M., Brann, D. W., Baban, B., & Dhandapani, K. M. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106090 · Cited by 49 · see citing works
“With respect to cell type(s), post-mitotic neurons do not undergo senescence whereas glial senescence more readily occurs (Fielder et al., 2017; Moreno-Blas et al., 2019; Chinta et al., 2013; Cohen and Torres, 2019; Han et al., 2020).”
Role of astrocytes in major neurological disorders: The evidence and implications
Scuderi, C., Stecca, C., Iacomino, A., & Steardo, L. (2013) · IUBMB Life · doi:10.1002/iub.1223 · Cited by 47 · see citing works
“For the idiopathic or nonfamilial forms of PD, the prevailing view is that the causes are multifactorial and that genetic predispositions, environmental toxins, and aging are likely to be important factors in disease initiation and progression (32).”
BackgroundThe role of cellular senescence in aging through the prism of Koch-like criteria
Yanai, H., & Fraifeld, V. E. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2017.10.004 · Cited by 45 · see citing works
Cellular Senescence, Neurological Function, and Redox State
Maciel-Barón, L. Á., Moreno-Blas, D., Morales-Rosales, S. L., González‐Puertos, V. Y., López‐Díazguerrero, N. E., Torres, C. A., Castro‐Obregón, S., & Königsberg, M. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7112 · Cited by 45 · see citing works
“…senescence occurs both in vitro and in vivo (46) and it has been associated with many biological processes such as aging (21), tumor suppression and promotion (23, 137), chronic inflammation (20), embryonic development (118, 156), and recently with neurodegenerative diseases (NDDs) (11, 13, 35).”
Immune-mediated processes in neurodegeneration: where do we stand?
Fakhoury, M. (2016) · Journal of Neurology · doi:10.1007/s00415-016-8052-0 · Cited by 43 · see citing works
“Although a primary cause for PD is yet to be determined, several risk factors have been identified, including aging, genetic predisposition and environmental insults [124, 125].”
BackgroundThe degeneration and replacement of dopamine cells in Parkinson’s disease: the role of aging
Rodrı́guez, M., Moráles, I., Rodriguez‐Sabate, C., Sánchez, A., Castro, R., Armas, J. M. B., & Sabaté, M. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00080 · Cited by 42 · see citing works
Coppari, S., Colomba, M., Fraternale, D., Brinkmann, V., Romeo, M., Rocchi, M., Giacomo, B. D., Mari, M., Guidi, L., Ramakrishna, S., et al. (2021) · Antioxidants · doi:10.3390/antiox10030374 · Cited by 42 · see citing works
The Emerging Role of Accelerated Cellular Senescence in Periodontitis
Aquino-Martinez, R. (2023) · Journal of dentistry research · doi:10.1177/00220345231154567 · Cited by 39 · see citing works
“Environmental toxins can also induce cellular senescence and eventually promote age-related diseases (Chinta et al. 2013).”
Backgroundβ-Catenin and TCFs/LEF signaling discordantly regulate IL-6 expression in astrocytes
Robinson, K. F., Narasipura, S. D., Wallace, J., Ritz, E. M., & Al‐Harthi, L. (2020) · Cell Communication and Signaling · doi:10.1186/s12964-020-00565-2 · Cited by 41 · see citing works
Mazzini, L., Vescovi, A. L., Cantello, R. M., Gelati, M., & Vercelli, A. (2015) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2016.1116516 · Cited by 38 · see citing works
“Moreover, recent studies suggest that even during normal aging, astrocytes become less supportive to MNs,[18,19] suggesting also a role of aging in the significant MN death related to astrocytes in a rodent model of familial ALS.”
BackgroundGonzález‐Giraldo, Y., Forero, D. A., Echeverrı́a, V., González, J., Ávila-Rodriguez, M., García‐Segura, L. M., & Barreto, G. E. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.04.004 · Cited by 38 · see citing works
Bcl-xL as a Modulator of Senescence and Aging
Mas‐Bargues, C., Borrás, C., & Viña, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041527 · Cited by 38 · see citing works
“Similarly, cell senescence has been related to neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases [70,71].”
BackgroundSIPS as a model to study age-related changes in proteolysis and aggregate formation
Ott, C., Jung, T., Grune, T., & Höhn, A. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.07.007 · Cited by 37 · see citing works
Nutrition and cellular senescence in obesity-related disorders
Rubio‐Tomás, T., Rueda‐Robles, A., Plaza‐Díaz, J., & Álvarez‐Mercado, A. I. (2021) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2021.108861 · Cited by 37 · see citing works
Alternative polyadenylation and the stress response
Sadek, J., Omer, A., Hall, D. T., Ashour, K., & Gallouzi, I. (2019) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1540 · Cited by 34 · see citing works
“Parkinson's disease (PD) is an age-related neurodegenerative disorder associated with loss of dopamine (DA) neurons within the midbrain and the appearance of α-synuclein containing protein aggregates within neurons termed Lewy bodies (Chinta et al., 2013; Rhinn et al., 2012).”
BackgroundDwivedi, V., & Lakhotia, S. C. (2016) · Journal of Biosciences · doi:10.1007/s12038-016-9641-x · Cited by 34 · see citing works
Cellular Senescence in Traumatic Brain Injury: Evidence and Perspectives
Schwab, N., Leung, E., & Hazrati, L. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.742632 · Cited by 33 · see citing works
“Glial cell senescence is better established (Chinta et al., 2013; Cohen and Torres, 2019; Han et al., 2020) and is typically assessed based on the assays mentioned here.”
BackgroundMaciel-Barón, L. Á., Morales-Rosales, S. L., Silva‐Palacios, A., Rodríguez‐Barrera, R., García, J. A., Luna‐López, A., Pérez, V., Torres, C. A., & Königsberg, M. (2018) · Biogerontology · doi:10.1007/s10522-018-9767-3 · Cited by 32 · see citing works
The far-reaching HAND of cART: cART effects on astrocytes
Gonzalez, H., Podany, A. T., Al‐Harthi, L., & Wallace, J. (2020) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-020-09907-w · Cited by 31 · see citing works
Connecting the dots: Neuronal senescence, stress granules, and neurodegeneration
Ma, Y., & Farny, N. G. (2023) · Gene · doi:10.1016/j.gene.2023.147437 · Cited by 30 · see citing works
Chamoli, M., Chinta, S. J., & Andersen, J. K. (2018) · Journal of Neural Transmission · doi:10.1007/s00702-018-1887-z · Cited by 30 · see citing works
Induction of a Senescence-Like Phenotype in Cultured Human Fetal Microglia During HIV-1 Infection
Chen, N. C., Partridge, A. T., Tüzer, F., Cohen, J., Nacarelli, T., Navas, S., Sell, C., Torres, C. A., & Martín‐García, J. (2018) · The Journals of Gerontology Series A · doi:10.1093/gerona/gly022 · Cited by 30 · see citing works
Greenberg, E. F., Voorbach, M. J., Smith, A. G., Reuter, D. R., Zhuang, Y., Wang, J.-Q., Wooten, D., Asque, E., Hu, M., Hoft, C., et al. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e36483 · Cited by 29 · see citing works
“Indeed, senescence has been directly linked to the pathophysiology of PD [37,77], MS [78,79], and ALS [80,81], and senomodulators have shown DMT effects in preclinical PD models [82].”
BackgroundRole of Inflammasomes in HIV-1 and Drug Abuse Mediated Neuroinflammaging
Sil, S., Niu, F., Chivero, E. T., Singh, S., Periyasamy, P., & Buch, S. J. (2020) · Cells · doi:10.3390/cells9081857 · Cited by 28 · see citing works
The Role of Kinase Modulators in Cellular Senescence for Use in Cancer Treatment
Lee, C. W., Baek, J., & Han, S. (2017) · Molecules · doi:10.3390/molecules22091411 · Cited by 28 · see citing works
“Cellular senescence is also thought to play a role in pathological processes, including liver fibrosis [44], renal fibrosis [45], cardiac fibrosis [46], vascular diseases (atherosclerosis) [47,48], metabolic diseases (obesity [49], type 2 diabetes [50]), neurological disorders (Alzheimer’s disease [51], Parkinson’s di…”
BackgroundQiu, W., Li, X., Shi, D., Li, X., Gao, Y. J., Li, J., Mao, F., Guo, Y., & Li, J. (2020) · Dyes and Pigments · doi:10.1016/j.dyepig.2020.108657 · Cited by 27 · see citing works
Revolutionizing Diabetic Foot Ulcer Care: The Senotherapeutic Approach
Zhang, G., Samarawickrama, P. N., Gui, L., Ma, Y., Cao, M., Zhu, H., Li, W., Yang, H., Li, K., Yang, Y., et al. (2024) · Aging and Disease · doi:10.14336/ad.2024.0065 · Cited by 27 · see citing works
Mursaleen, L., Noble, B., Somavarapu, S., & Zariwala, M. G. (2021) · Antioxidants · doi:10.3390/antiox10060887 · Cited by 26 · see citing works
Autophagy and heat-shock response impair stress granule assembly during cellular senescence
Omer, A., Patel, D. M., Moran, J. L., Lian, X. J., Marco, S. D., & Gallouzi, I. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111382 · Cited by 25 · see citing works
Induction, regulation and roles of neural adhesion molecule L1CAM in cellular senescence
Mrázková, B., Dzijak, R., Hornofova, T., Kyjacová, L., Baráth, P., Džubák, P., Holub, D., Hajdúch, M., Nahácka, Z., Anděra, L., et al. (2018) · Aging · doi:10.18632/aging.101404 · Cited by 23 · see citing works
“Indeed, there is accumulating evidence that SC contribute to pathogenesis of several aging-associated degenerative diseases including atherosclerosis [21], cartilage degeneration leading to osteoarthritis [22, 23], cardiac fibrosis [24], liver fibrosis [25], type 2 diabetes [26], and Alzheimer’s and Parkinson’s diseas…”
BackgroundMyricetin reduces cytotoxicity by suppressing hepcidin expression in MES23.5 cells
Deng, H., Liu, S., Pan, D., Jia, Y., & Ma, Z. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.300461 · Cited by 23 · see citing works
“Studies have shown that many factors are involved in rotenone-induced dopamine neurotoxicity, including inhibition of mitochondrial complex I (Betarbet et al., 2000; Chinta et al., 2013), ROS production, and oxidative damage of proteins, lipids, and DNA.”
Cordaro, M., Modafferi, S., D’Amico, R., Fusco, R., Genovese, T., Peritore, A. F., Gugliandolo, E., Crupi, R., Interdonato, L., Paola, D. D., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10102505 · Cited by 24 · see citing works
“The brains of five mice in every group were fixed, sliced, and stained with hematoxylin and eosin (H&E, Bio-Optica, Milan, Italy), and the sections were evaluated using an optical microscope linked to an imaging system (Leica Microsystems SpA), as earlier described [34,45].”
MethodNeault, M., Couteau, F., Bonneau, É., Guire, V. D., & Mallette, F. A. (2017) · International review of cytology · doi:10.1016/bs.ircmb.2017.04.001 · Cited by 22 · see citing works
Designing in vitro Blood-Brain Barrier Models Reproducing Alterations in Brain Aging
Osipova, E. D., Komleva, Y. K., Morgun, A. V., Lopatina, O. L., Panina, Y. A., Olovyannikova, R. Y., Vais, E. F., Salmin, V. V., & Salmina, A. B. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00234 · Cited by 23 · see citing works
“Aging-associated progressive telomere shortening and development of SASP occur in astroglial and endothelial cells (Bitto et al., 2010; Chinta et al., 2013; Morgan et al., 2018), thus contributing to local production of pro-inflammatory cytokines.”
BackgroundBilirubin: A Promising Therapy for Parkinson’s Disease
Jayanti, S. D., Moretti, R., Tiribelli, C., & Gazzin, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126223 · Cited by 22 · see citing works
“Moreover, the inflammatory responses of microglia are amplified by astrocyte senescence in the aging brain [55,56].”
BackgroundImmunity impacts cognitive deficits across neurological disorders
Shaw, B. C., Anders, V., Tinkey, R. A., Habean, M. L., Brock, O. D., Frostino, B. J., & Williams, J. L. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15999 · Cited by 26 · see citing works
“…cytokines by resident glial cells has been iden - tified as a plausible catalyst for age-related, exacerbated inflam - mation associated with PD onset and its accompanying cognitive deficits (Chinta et al., 2013 ; Krizhanovsky et al., 2008 ; Mukhara et al., 2020 ; Thomas et al., 2021 ).”
Jia, F., Song, N., Zhao, C., Xie, J., & Jiang, H. F. (2014) · PLoS ONE · doi:10.1371/journal.pone.0091641 · Cited by 21 · see citing works
“Rotenone, which is commonly used as a liposoluble insecticide, is widely believed to be a high-affinity, specific inhibitor of mitochondrial complex I [18,19].”
BackgroundSuperAgers and centenarians, dynamics of healthy ageing with cognitive resilience
Islam, M. A., Sehar, U., Sultana, O. F., Mukherjee, U., Brownell, M., Kshirsagar, S., & Reddy, P. H. (2024) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2024.111936 · Cited by 21 · see citing works
Epigenetic clocks suggest accelerated aging in patients with isolated REM Sleep Behavior Disorder
Baldelli, L., Pirazzini, C., Sambati, L., Ravaioli, F., Gentilini, D., Buonaura, G. C., Guaraldi, P., Franceschi, C., Cortelli, P., Garagnani, P., et al. (2023) · npj Parkinson s Disease · doi:10.1038/s41531-023-00492-2 · Cited by 20 · see citing works
Krejciova, Z., Carlson, G. A., Giles, K., & Prusiner, S. B. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0703-9 · Cited by 19 · see citing works
Díaz, J., Martínez‐Martín, P., Rodríguez‐Blázquez, C., Vázquez, B., Forjaz, M. J., Ortíz, C., Carmona, R., & Linares, C. (2017) · Gaceta Sanitaria · doi:10.1016/j.gaceta.2017.01.005 · Cited by 19 · see citing works
A large-scale CRISPR screen and identification of essential genes in cellular senescence bypass
Liu, X., Wei, L., Dong, Q., Liu, L., Zhang, M. Q., Xie, Z., & Wang, X. (2019) · Aging · doi:10.18632/aging.102034 · Cited by 19 · see citing works
“The accumulation of senescent cells in the brain may cause chronic inflammation by SASP, affecting the pathogenesis of Alzheimer’s disease [35] and Parkinson’s disease [36].”
BackgroundAstrocytes in Parkinson's disease: from preclinical assays to in vivo imaging and therapeutic probes
Zeng, Z., Roussakis, A., Lao–Kaim, N. P., & Piccini, P. P. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.07.012 · Cited by 17 · see citing works
Solving the puzzle of Parkinson’s disease using induced pluripotent stem cells
Zhao, P., Luo, Z., Tian, W., Yang, J., Ibañez, D. P., Huang, Z., Tortorella, M. D., Esteban, M. A., & Fan, W. (2014) · Experimental Biology and Medicine · doi:10.1177/1535370214538588 · Cited by 16 · see citing works
“PD is a chronic disease in which environmental factors and age play key roles.(77) The latter is especially relevant in idiopathic cases but also applies to PD patients bearing mutations in LRRK2 or SNCA.”
BackgroundMechanisms of neurotoxicity and implications for neurological disorders
Ceccatelli, S. (2013) · Journal of Internal Medicine · doi:10.1111/joim.12053 · Cited by 16 · see citing works
Cellular Senescence in Glial Cells: Implications for Multiple Sclerosis
Maupin, E. A., & Adams, K. L. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.16301 · Cited by 12 · see citing works
Optimization of Parkinson's disease therapy with plant extracts and nutrition’s evolving roles
Abolarin, P. O., Amin, A., Nafiu, A. B., Ogundele, O. M., & Owoyele, B. V. (2024) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2024.05.011 · Cited by 20 · see citing works
“This inflammatory process in the due course results in the generation of cellular senescence in the brain neurons (Ceccatelli et al., 2013; Chinta et al., 2013).”
BackgroundPirazzini, C., Azevedo, T., Baldelli, L., Bartoletti‐Stella, A., Buonaura, G. C., Molin, A. D., Dimitri, G. M., Doykov, I., Gómez‐Garre, P., Hägg, S., et al. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111426 · Cited by 15 · see citing works
Song, I. Y., Snyder, A. M., Kim, Y., Neely, E. B., Wade, Q. W., & Connor, J. R. (2020) · Toxicology · doi:10.1016/j.tox.2020.152525 · Cited by 15 · see citing works
“Astrocytes in senescence secrete and release pro-inflammatory cytokines that ultimately damage the neighboring cells, especially neurons (Chinta et al. 2013).”
Background
- Authors
- Chinta, S. J., Lieu, C. A., DeMaria, M., Laberge, R. ‐., Campisi, J., & Andersen, J. K.
- Affiliations
- Buck Institute for Research on Aging (US)
- Corresponding author
- Andersen, J. K.
- Venue
- Journal of Internal Medicine
- Publisher
- Wiley
- Published
- 2013-04-22
- Volume
- 273
- Issue
- 5
- Pages
- 429-436
- ISSN
- 0954-6820 (ISSN-L)
- 1365-2796
- PMC
- PMC3633085
- OpenAlex
- W2001965479
- Cited by
- 165
- References
- 85
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 11 · 2023: 13 · 2022: 10 · 2021: 10 · 2020: 19 · 2019: 16 · 2018: 15 · 2017: 15 · 2016: 16 · 2015: 9 · 2014: 9 · 2013: 3
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes on Aging (AG025901)
- California Institute of Regenerative Medicine (TG2-01155)
- American Italian Cancer Foundation
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- Parkinson's disease, cellular senescence, senescence-associated secretory phenotype, environmental toxins, environmental stress, brain aging, neuroinflammation, glial activation, neurodegeneration, age-related diseases
- MeSH terms
- Aging, Environmental Exposure, Environmental Pollutants, Humans, Neuroglia, Parkinson Disease, Phenotype, Time Factors, Signal Transduction, Cellular Senescence, Inflammation Mediators
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