Mitochondria are required for pro-ageing features of the senescent phenotype
Open accessAbstract
Cell senescence is an important tumour suppressor mechanism and driver of ageing. Both functions are dependent on the development of the senescent phenotype, which involves an overproduction of pro‐inflammatory and pro‐oxidant signals. However, the exact mechanisms regulating these phenotypes remain poorly understood. Here, we show the critical role of mitochondria in cellular senescence. In multiple models of senescence, absence of mitochondria reduced a spectrum of senescence effectors and phenotypes while preserving ATP production via enhanced glycolysis. Global transcriptomic analysis by RNA sequencing revealed that a vast number of senescent‐associated changes are dependent on mitochondria, particularly the pro‐inflammatory phenotype. Mechanistically, we show that the ATM, Akt and mTORC1 phosphorylation cascade integrates signals from the DNA damage response (DDR) towards PGC‐1β‐dependent mitochondrial biogenesis, contributing to a ROS‐mediated activation of the DDR and cell cycle arrest. Finally, we demonstrate that the reduction in mitochondrial content in vivo , by either mTORC1 inhibition or PGC‐1β deletion, prevents senescence in the ageing mouse liver. Our results suggest that mitochondria are a candidate target for interventions to reduce the deleterious impact of senescence in ageing tissues.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
There is evidence for reciprocal influence between nuclear DNA damage and mitochondrial dysfunction.
“There is evidence in support of a reciprocal influence between nuclear DNA damage and mitochondrial dysfunction48”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [48]
The Results sections on PGC-1β-dependent biogenesis and ROS-driven DNA damage foci (page not provided) show influence in both directions: DNA damage response increases mitochondrial mass, while mitochondrial biogenesis and ROS help maintain DNA damage foci. The paper does not establish that nuclear DNA damage causes mitochondrial dysfunction specifically; the mitochondrial change it demonstrates is increased biogenesis. (LLM, conf=0.84)
Experimental — accuracy not yet measuredTargeting aspects of mitochondrial biology such as the electron transport chain, complex I assembly, mitochondrial fission rates, biogenesis, mitochondrial sirtuins, and/or disruption of the TCA cycle can trigger senescence.
“Targeting aspects of mitochondrial biology, such as the electron transport chain (ETC), complex I assembly, mitochondrial fission rates, and biogenesis, mitochondrial sirtuins and/or disruption of the TCA cycle can trigger senescence (Correia-Melo et al., 2016; Jiang et al., 2013; Kaplon et al., 2013; Miwa et al., 2014; Moiseeva et al., 2009; Park et al., 2010; Wiley et al., 2016).”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Correia-Melo et al., 2016
The Discussion says interventions affecting the electron transport chain enhance oncogene-induced senescence, and the Introduction links PGC-1β-dependent mitochondrial biogenesis to cellular senescence. These passages support the ETC and biogenesis examples, but they do not establish that targeting complex I assembly, fission rates, mitochondrial sirtuins, or the TCA cycle triggers senescence. Page numbers are not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMitochondrial dysfunction during senescence can result in ROS-driven lipid damage, lipid deposits, and lipofuscin accumulation.
“Mitochondrial dysfunction during senescence can result in ROS-driven lipid damage, lipid deposits (Correia-Melo et al., 2016; Ogrodnik et al., 2017), and lipofuscin accumulation (Gorgoulis et al., 2018).”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Correia-Melo et al., 2016
The Results section reports that depleting mitochondria reduced ROS generation in senescent cells, supporting the mitochondrial ROS part of the claim. It does not report ROS-driven lipid damage or lipid deposits. Lipofuscin accumulation is attributed to a different citation in the citing sentence. (LLM, conf=0.86)
Experimental — accuracy not yet measuredInterventions known to increase health span such as dietary restriction, exercise, rapamycin and 17β-oestradiol can reduce the frequency of cells with TAFs.
“First, interventions known to increase health span such as dietary restriction41, exercise42, rapamycin43,44 and 17β-oestradiol45 can reduce the frequency of cells with TAFs.”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [43]
Mitophagy in senescent cells appears to suppress the SASP.
“Mitophagy (mitochondrial clearance) in senescent cells appears to suppress the SASP (Correia-Melo et al., 2016).”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Correia-Melo et al., 2016
Dysfunctional mitochondria, persistent DNA damage response, C/EBPβ and NF-κB, mTOR, and other factors are involved in regulating SASP.
“Furthermore, dysfunctional mitochondria,195 persistent DNA damage response,196 CCAAT/enhancer-binding protein β (C/EBPβ) and NF-κB,197 mTOR, and other factors are involved in regulating SASP.194”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [195]
Altered mitochondrial function appears essential in mediating the senescence phenotype.
“Altered mitochondrial function appears essential in mediating the senescence phenotype.”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [60]
Many cells undergo senescence independently of telomere shortening due to replicative, mitochondrial, oxidative, metabolic, or genotoxic stress.
“Many cells undergo senescence independently of telomere shorting due to replicative, mitochondrial, oxidative, metabolic, or genotoxic stress (Parrinello et al., 2003; Christoffersen et al., 2010; Correia-Melo et al., 2016; Nair et al., 2015).”
From DNA damage-how and why we age? (2021) · cites this paper as Correia-Melo et al., 2016
A DNA damage response can induce mitochondrial ROS, partially dependent on activation of p53 and p21 pathways and on signals from ATM towards mTORC1.
“We have shown that a DNA damage response can induce mitochondrial ROS and this is partially dependent on the activation of p53 and p21 pathways, but also signals from ATM towards mTORC1 (Passos et al., 2010, Correia-Melo et al., 2016).”
From Telomeres and cell senescence—size matters not (2017) · cites this paper as Correia-Melo et al., 2016
Mitochondrial ablation or inhibition of mtROS formation in senescent cells inhibits the SASP and prevents CCF formation, suggesting mito-nuclear communication contributes to CCF formation.
“Interestingly, mitochondrial ablation from senescent cells, or inhibition of mtROS formation, inhibits the SASP and prevents the formation of CCF, suggesting that mito-nuclear communication plays a role in CCF formation (Correia-Melo et al., 2016; Vizioli et al., 2020).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Correia-Melo et al., 2016
Inhibition of the mTOR pathway (using rapamycin), which extends lifespan in a variety of model organisms, is an effective SASP suppressor.
“For instance, inhibition of the mTOR pathway (using the drug rapamycin), which has been shown to extend lifespan in a variety of model organisms (de Magalhaes et al., 2012;Harrison et al., 2009), is an effective SASP suppressor (Correia-Melo et al., 2016;Herranz et al., 2015;Laberge et al., 2015).”
From Stress, cell senescence and organismal ageing (2018) · cites this paper as Correia-Melo et al., 2016
Removal of mitochondria in senescent cells disrupts the feedforward cycle involving ROS production and persistent DDR activation, while preserving cell cycle arrest.
“Removal of mitochondria in senescent cells disrupts the feedforward cycle that involves ROS production and persistent DDR activation, while preserving their cell cycle arrest [215].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [215]
During senescence, mTORC1 activation due to sustained DDR promotes mitochondrial biogenesis, contributing to ROS-dependent DDR persistence and SASP regulation.
“Similarly, during senescence, mTORC1 activation due to sustained DDR does not favor growth but promotes mitochondrial biogenesis, thus contributing to the ROS-dependent DDR persistence and to SASP regulation [215].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [215]
The switch from transient to irreversible growth arrest involves positive feedback loops in which mitochondrial dysfunction via ROS, pro-inflammatory SASP factors, extensive chromatin remodeling, and/or nuclear lamina and chromatin degradation reinforce DDR signaling.
“The switch from transient to irreversible growth arrest involves positive feedback loops in which mitochondrial dysfunction via ROS [215,250], pro-inflammatory SASP factors [147,154,252], extensive chromatin remodeling [253], and/or nuclear lamina and chromatin degradation [105,171,247] reinforce DDR signaling (Figure 3).”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [215]
Escalating ROS production by dysfunctional mitochondria aggravates nuclear DNA damage and stabilizes chronic DDR activation, contributing to maintenance of the pro-inflammatory and pro-oxidant senescent phenotype upon DNA damage.
“The escalating ROS production by dysfunctional mitochondria aggravates nuclear DNA damage and stabilizes the chronic DDR activation, contributing to the maintenance of the pro-inflammatory and pro-oxidant senescent phenotype upon DNA damage [215,250].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [215]
Selective and specific removal of mitochondria in senescent cells normalizes ROS levels.
“Indeed, the selective and specific removal of mitochondria in senescent cells normalizes ROS levels [215].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [215]
Mitochondrial dysfunction is the main cause of elevated ROS production in senescence.
“Mitochondrial dysfunction is the main cause of elevated ROS production in senescence.”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [215]
Muscle mitochondria are important regulators of muscle size.
“Together, these observations support for the idea that muscle mitochondria are important regulators of muscle size.”
From Mitochondria initiate and regulate sarcopenia (2017) · cites this paper as [31]
Knockout of Mfn1/2 in skeletal muscle prevented mitochondrial fusion, increased mtDNA defects, and resulted in muscle atrophy.
“a knockout of Mfn 1/2 in skeletal muscle, which prevented mitochondrial fusion, increased the accumulation of mtDNA defects and resulted in muscle atrophy (31).”
From Mitochondria initiate and regulate sarcopenia (2017) · cites this paper as [31]
DNA damage response induced by stress or cell replication activates mitochondrial biogenesis, which mediates cell cycle arrest.
“Recently, Correia‐Melo et al. (2016) reported that DNA damage response (DDR) [induced by stress (i.e., ROS) or cell replication] activates mitochondrial biogenesis which will mediate a cell cycle arrest.”
From Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism (2017) · cites this paper as Correia‐Melo et al. (2016)
Reduction in mitochondrial content by mTORC1 inhibition prevents cellular senescence.
“Interestingly, they showed that the reduction in mitochondrial content by mTORC1 inhibition prevents cellular senescence.”
From Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism (2017) · cites this paper as Correia‐Melo et al. (2016)
Mitochondrial dysfunction has been described as both a driver and consequence of cellular senescence.
“Mitochondrial dysfunction has been described as both a driver and consequence of cellular senescence”
From Length-independent telomere damage drives post-mitotic cardiomyocyte senescence (2019) · cites this paper as Correia‐Melo et al, 2016
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668 · see citing works
mTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509 · see citing works
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477 · see citing works
Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
Narendra, D., Tanaka, A., Suen, D.-F., & Youle, R. J. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200809125 · Cited by 4,026 · see citing works
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766 · see citing works
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · cited 1× · see citing works
“Cellular senescence, the irreversible loss of proliferative potential in somatic cells, has been shown to not only play a major role in tumour suppression, but also to contribute to age-related tissue degeneration (Baker et al , 2011).”
Differential analysis of gene regulation at transcript resolution with RNA-seq
Trapnell, C., Hendrickson, D. G., Sauvageau, M., Goff, L., Rinn, J. L., & Pachter, L. (2013) · Nature Biotechnology · doi:10.1038/nbt.2450 · Cited by 3,492 · see citing works
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002) · Nature Cell Biology · doi:10.1038/ncb839 · Cited by 3,083 · see citing works
A DNA damage checkpoint response in telomere-initiated senescence
Fagagna, F. D. D., Reaper, P. M., Clay-Farrace, L., Fiegler, H., Carr, P., von Zglinicki, T., Saretzki, G., Carter, N. P., & Jackson, S. P. (2003) · Nature · doi:10.1038/nature02118 · Cited by 2,855 · cited 1× · see citing works
“Activation of a DDR is a prominent initiator of senescence during stress-induced (Passos et al , 2010), replicative (d’Adda di Fagagna et al , 2003) and oncogene-induced senescence (OIS) (Suram et al , 2012).”
Self-citationPINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
Geisler, S., Holmström, K. M., Skujat, D., Fiesel, F. C., Rothfuss, O. C., Kahle, P. J., & Springer, W. (2010) · Nature Cell Biology · doi:10.1038/ncb2012 · Cited by 2,835 · see citing works
Oxidative stress shortens telomeres
von Zglinicki, T. (2002) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(02)02110-2 · Cited by 2,524 · see citing works
A complex secretory program orchestrated by the inflammasome controls paracrine senescence
Acosta, J. C., Banito, A., Wuestefeld, T., Georgilis, A., Janich, P., Morton, J. P., Athineos, D., Kang, T.-W., Lasitschka, F., Andrulis, M., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2784 · Cited by 2,278 · see citing works
Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232 · see citing works
Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network
Kuilman, T., Michaloglou, C., Vredeveld, L. C. W., Douma, S., van Doorn, R., Desmet, C. J., Aarden, L. A., Mooi, W. J., & Peeper, D. S. (2008) · Cell · doi:10.1016/j.cell.2008.03.039 · Cited by 2,086 · cited 1× · see citing works
“These factors not only contribute to the maintenance of the senescence arrest via self-amplifying positive feedback loops (Acosta et al , 2008; Kuilman et al , 2008; Passos et al , 2010), but can also induce senescence in healthy cells in a paracrine fashion (Nelson et al , 2012; Acosta et al ,…”
A Mitochondrial Protein Compendium Elucidates Complex I Disease Biology
Pagliarini, D. J., Calvo, S. E., Chang, B., Sheth, S. A., Vafai, S. B., Ong, S.-E., Walford, G. A., Sugiana, C., Boneh, A., Chen, W. K., et al. (2008) · Cell · doi:10.1016/j.cell.2008.06.016 · Cited by 1,994 · see citing works
Chemokine signaling via the CXCR2 receptor reinforces senescence
Acosta, J. C., O'Loghlen, A., Banito, A., Guijarro, M. V., Augert, A., Raguz, S., Fumagalli, M., Da Costa, M., Brown, C., Popov, N., et al. (2008) · Cell · doi:10.1016/j.cell.2008.03.038 · Cited by 1,801 · cited 1× · see citing works
“These factors not only contribute to the maintenance of the senescence arrest via self-amplifying positive feedback loops (Acosta et al , 2008; Kuilman et al , 2008; Passos et al , 2010), but can also induce senescence in healthy cells in a paracrine fashion (Nelson et al , 2012; Acosta et al ,…”
Cellular senescence and the senescent secretory phenotype: therapeutic opportunities
Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J., & Kirkland, J. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64098 · Cited by 1,774 · see citing works
TRF2 Protects Human Telomeres from End-to-End Fusions
van Steensel, B., Smogorzewska, A., & de Lange, T. (1998) · Cell · doi:10.1016/s0092-8674(00)80932-0 · Cited by 1,709 · see citing works
mTOR controls mitochondrial oxidative function through a YY1–PGC-1α transcriptional complex
Cunningham, J. T., Rodgers, J. T., Arlow, D. H., Vazquez, F., Mootha, V. K., & Puigserver, P. (2007) · Nature · doi:10.1038/nature06322 · Cited by 1,488 · see citing works
Peroxisome proliferator–activated receptor γ coactivator-1 promotes cardiac mitochondrial biogenesis
Lehman, J. J., Barger, P. M., Kovacs, A., Saffitz, J. E., Medeiros, D. M., & Kelly, D. P. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10268 · Cited by 1,285 · see citing works
Laberge, R.-M., Sun, Y., Orjalo, A. V., Patil, C. K., Freund, A., Zhou, L., Curran, S. C., Davalos, A. R., Wilson-Edell, K. A., Liu, S., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3195 · Cited by 1,160 · see citing works
Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts
Parrinello, S., Samper, E., Krtolica, A., Goldstein, J., Melov, S., & Campisi, J. (2003) · Nature Cell Biology · doi:10.1038/ncb1024 · Cited by 1,116 · see citing works
Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS
Nisoli, E., Tonello, C., Cardile, A., Cozzi, V., Bracale, R., Tedesco, L., Falcone, S., Valerio, A., Cantoni, O., Clementi, E., et al. (2005) · Science · doi:10.1126/science.1117728 · Cited by 1,107 · see citing works
Feedback between p21 and reactive oxygen production is necessary for cell senescence
Passos, J. F., Nelson, G., Wang, C., Richter, T., Simillion, C., Proctor, C. J., Miwa, S., Olijslagers, S., Hallinan, J., Wipat, A., et al. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.5 · Cited by 1,019 · cited 6× · see citing works
“On the other hand, our data show that interventions targeting the mTOR pathway affect the maintenance of a DDR via the generation of ROS, which has been shown to be necessary for the induction of senescence and the SASP (Rodier et al , 2009; Passos et al , 2010).”
InfluentialSelf-citationWu, M., Neilson, A., Swift, A. L., Moran, R., Tamagnine, J., Parslow, D., Armistead, S., Lemire, K., Orrell, J., Teich, J., et al. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00247.2006 · Cited by 922 · see citing works
Senescence-messaging secretome: SMS-ing cellular stress
Kuilman, T., & Peeper, D. S. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2560 · Cited by 909 · see citing works
Hewitt, G., Jurk, D., Marques, F. D. M., Correia-Melo, C., Hardy, T., Gackowska, A., Anderson, R., Taschuk, M., Mann, J., & Passos, J. F. (2012) · Nature Communications · doi:10.1038/ncomms1708 · Cited by 908 · see citing works
Self-citationChronic inflammation induces telomere dysfunction and accelerates ageing in mice
Jurk, D., Wilson, C., Passos, J. F., Oakley, F., Correia-Melo, C., Greaves, L., Saretzki, G., Fox, C., Lawless, C., Anderson, R., et al. (2014) · Nature Communications · doi:10.1038/ncomms5172 · Cited by 814 · see citing works
Self-citationmTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype
Herranz, N., Gallage, S., Mellone, M., Wuestefeld, T., Klotz, S., Hanley, C. J., Raguz, S., Acosta, J. C., Innes, A. J., Banito, A., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3225 · Cited by 788 · see citing works
A senescent cell bystander effect: senescence‐induced senescence
Nelson, G., Wordsworth, J., Wang, C., Jurk, D., Lawless, C., Martin‐Ruiz, C., & von Zglinicki, T. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00795.x · Cited by 755 · see citing works
Self-citationChen, C., Liu, Y., Liu, R., Ikenoue, T., Guan, K.-L., Liu, Y., & Zheng, P. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20081297 · Cited by 682 · see citing works
A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence
Kaplon, J., Zheng, L., Meissl, K., Chaneton, B., Selivanov, V. A., Mackay, G., van der Burg, S. H., Verdegaal, E. M. E., Cascante, M., Shlomi, T., et al. (2013) · Nature · doi:10.1038/nature12154 · Cited by 633 · see citing works
Mitra, K., Wunder, C., Roysam, B., Lin, G., & Lippincott‐Schwartz, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904875106 · Cited by 625 · see citing works
Jurk, D., Wang, C., Miwa, S., Maddick, M., Korolchuk, V., Tsolou, A., Gonos, E. S., Thrasivoulou, C., Jill Saffrey, M., Cameron, K., et al. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00870.x · Cited by 598 · see citing works
Self-citationTakahashi, A., Ohtani, N., Yamakoshi, K., Iida, S.-I., Tahara, H., Nakayama, K., Nakayama, K. I., Ide, T., Saya, H., & Hara, E. (2006) · Nature Cell Biology · doi:10.1038/ncb1491 · Cited by 528 · see citing works
mTOR Inhibition Alleviates Mitochondrial Disease in a Mouse Model of Leigh Syndrome
Johnson, S. C., Yanos, M. E., Kayser, E., Quintana, A., Sangesland, M., Castanza, A. S., Uhde, L., Hui, J., Wall, V., Gagnidze, A., et al. (2013) · Science · doi:10.1126/science.1244360 · Cited by 520 · see citing works
Rogers, G. W., Brand, M. D., Petrosyan, S., Ashok, D., Elorza, Á. A., Ferrick, D. A., & Murphy, A. N. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021746 · Cited by 474 · see citing works
Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence
Moiseeva, O., Bourdeau, V., Roux, A., Deschênes-Simard, X., & Ferbeyre, G. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01868-08 · Cited by 408 · cited 3× · see citing works
“Chemical and genetic interventions impacting on the mitochondrial electron transport chain have been shown to enhance OIS (Moiseeva et al , 2009); however, to date, no study has effectively evaluated the necessity of mitochondria for the induction of the senescent phenotype.”
InfluentialThe efficiency and plasticity of mitochondrial energy transduction.
Brand, M. D. (2005) · Biochemical Society Transactions · doi:10.1042/bst0330897 · Cited by 406 · see citing works
Chimenti, C., Kajstura, J., Torella, D., Urbanek, K., Heleniak, H., Colussi, C., Di Meglio, F., Nadal-Ginard, B., Frustaci, A., Leri, A., et al. (2003) · Circulation Research · doi:10.1161/01.res.0000093985.76901.af · Cited by 386 · see citing works
Widespread Mitochondrial Depletion via Mitophagy Does Not Compromise Necroptosis
Tait, S. W. G., Oberst, A., Quarato, G., Milasta, S., Haller, M., Wang, R., Karvela, M., Ichim, G., Yatim, N., Albert, M. L., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.10.034 · Cited by 303 · see citing works
Self-citationCoppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302 · see citing works
PRAS40 and PRR5-Like Protein Are New mTOR Interactors that Regulate Apoptosis
Thedieck, K., Polak, P., Kim, M. L., Molle, K. D., Cohen, A., Jenö, P., Arrieumerlou, C., & Hall, M. N. (2007) · PLoS ONE · doi:10.1371/journal.pone.0001217 · Cited by 290 · see citing works
Sone, H., & Kagawa, Y. (2005) · Diabetologia · doi:10.1007/s00125-004-1605-2 · Cited by 286 · see citing works
Iglesias-Bartolome, R., Patel, V., Cotrim, A., Leelahavanichkul, K., Molinolo, A. A., Mitchell, J. B., & Gutkind, J. S. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.06.007 · Cited by 284 · see citing works
Osorio, F. G., Bárcena, C., Soria-Valles, C., Ramsay, A. J., de Carlos, F., Cobo, J., Fueyo, A., Freije, J. M. P., & López-Otín, C. (2012) · Genes & Development · doi:10.1101/gad.197954.112 · Cited by 276 · see citing works
Full Activation of PKB/Akt in Response to Insulin or Ionizing Radiation Is Mediated through ATM
Viniegra, J. G., Martínez, N., Modirassari, P., Hernández‐Losa, J., Cobo, C. P., Lobo, V. J. S.-A., Luquero, C. I. A., Álvarez‐Vallina, L., y Cajal, S. R., Rojas, J. M., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410344200 · Cited by 270 · see citing works
Suram, A., Kaplunov, J., Patel, P. L., Ruan, H., Cerutti, A., Boccardi, V., Fumagalli, M., Di Micco, R., Mirani, N., Gurung, R. L., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.132 · Cited by 227 · see citing works
Lanza, I. R., Zabielski, P., Klaus, K. A., Morse, D. M., Heppelmann, C. J., Bergen, H. R., Dasari, S., Walrand, S., Short, K. R., Johnson, M. L., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.11.003 · Cited by 227 · see citing works
Empirical methods for controlling false positives and estimating confidence in ChIP-Seq peaks
Nix, D. A., Courdy, S., & Boucher, K. M. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-523 · Cited by 225 · see citing works
Low abundance of the matrix arm of complex I in mitochondria predicts longevity in mice
Miwa, S., Jow, H., Baty, K., Johnson, A. J., Czapiewski, R., Saretzki, G. C., Treumann, A., & von Zglinicki, T. (2014) · Nature Communications · doi:10.1038/ncomms4837 · Cited by 207 · see citing works
Self-citationTelomeres, oxidative stress and inflammatory factors: partners in cellular senescence?
Correia‐Melo, C., Hewitt, G., & Passos, J. F. (2014) · Longevity & Healthspan · doi:10.1186/2046-2395-3-1 · Cited by 195 · see citing works
Self-citationSuperoxide Dismutase 1 Knock-down Induces Senescence in Human Fibroblasts
Blander, G., de Oliveira, R. M., Conboy, C. M., Haigis, M., & Guarente, L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307146200 · Cited by 183 · see citing works
Birket, M. J., Orr, A. L., Gerencser, A. A., Madden, D. T., Vitelli, C., Swistowski, A., Brand, M. D., & Zeng, X. (2011) · Journal of Cell Science · doi:10.1242/jcs.072272 · Cited by 169 · see citing works
Endothelial PGC-1α Mediates Vascular Dysfunction in Diabetes
Sawada, N., Jiang, A., Takizawa, F., Safdar, A., Manika, A., Tesmenitsky, Y., Kang, K.-T., Bischoff, J. E., Kalwa, H., Sartoretto, J. L., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.12.014 · Cited by 163 · see citing works
Lee, C., Inoki, K., Karbowniczek, M., Petroulakis, E., Sonenberg, N., Henske, E. P., & Guan, K. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601900 · Cited by 160 · see citing works
Adult-onset, short-term dietary restriction reduces cell senescence in mice
Wang, C., Maddick, M., Miwa, S., Jurk, D., Czapiewski, R., Saretzki, G., Langie, S. A. S., Godschalk, R. W. L., Cameron, K., & von Zglinicki, T. (2010) · Aging · doi:10.18632/aging.100196 · Cited by 142 · see citing works
Self-citationUrano, J., Sato, T., Matsuo, T., Otsubo, Y., Yamamoto, M. P., & Tamanoi, F. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608510104 · Cited by 140 · see citing works
PREPARATION OF MITOCHONDRIA FROM ANIMAL TISSUES AND YEASTS
Chappell, J., & Hansford, R. G. (1972) · Elsevier eBooks · doi:10.1016/b978-0-408-70360-4.50009-2 · Cited by 136 · see citing works
Does calorie restriction induce mitochondrial biogenesis? A reevaluation
Hancock, C. R., Han, D., Higashida, K., Kim, S. H., & Holloszy, J. O. (2011) · The FASEB Journal · doi:10.1096/fj.10-170415 · Cited by 131 · see citing works
S6K1 is a multifaceted regulator of Mdm2 that connects nutrient status and DNA damage response
Lai, K. P., Leong, W. F., Chau, J. F. L., Jia, D., Zeng, L., Liu, H., He, L., Hao, A., Zhang, H., Meek, D. W., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.166 · Cited by 130 · see citing works
Ning, Y., Cai, G., Zhuo, L., Gao, J., Dong, D. F., Cui, S., Feng, Z., Shi, S., Bai, X., Sun, X., et al. (2013) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2013.11.006 · Cited by 91 · see citing works
Price, J. C., Khambatta, C. F., Li, K. W., Bruss, M. D., Shankaran, M., Dalidd, M., Floreani, N. A., Roberts, L. S., Turner, S., Holmes, W. E., et al. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.021204 · Cited by 84 · see citing works
Suppression of replicative senescence by rapamycin in rodent embryonic cells
Pospelova, T. V., Leontieva, O. V., Bykova, T. V., Zubova, S. G., Pospelov, V. A., & Blagosklonny, M. V. (2012) · Cell Cycle · doi:10.4161/cc.20882 · Cited by 83 · see citing works
Romanino, K., Mazelin, L., Albert, V., Conjard‐Duplany, A., Lin, S., Bentzinger, C. F., Handschin, C., Puigserver, P., Zorzato, F., Schaeffer, L., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1111448109 · Cited by 44 · see citing works
IHG-1 Promotes Mitochondrial Biogenesis by Stabilizing PGC-1α
Hickey, F. B., Corcoran, J. B., Docherty, N. G., Griffin, B., Bhreathnach, Ú., Furlong, F. M., Martin, F., Godson, C., & Murphy, M. (2011) · Journal of the American Society of Nephrology · doi:10.1681/asn.2010111154 · Cited by 40 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cellular Senescence: Defining a Path Forward
Gorgoulis, V., Adams, P. D., Alimonti, A., Bennett, D. C., Bischof, O., Bishop, C., Campisi, J., Collado, M., Evangelou, K., Ferbeyre, G., et al. (2019) · Cell · doi:10.1016/j.cell.2019.10.005 · Cited by 3,225 · see citing works
Self-citationHallmarks of Cellular Senescence
Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.001 · Cited by 2,605 · see citing works
Cellular senescence in ageing: from mechanisms to therapeutic opportunities
Di Micco, R., Krizhanovsky, V., Baker, D., & d’Adda di Fagagna, F. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00314-w · Cited by 2,277 · see citing works
Inflammation and aging: signaling pathways and intervention therapies
Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01502-8 · Cited by 1,443 · see citing works
Mechanisms and functions of cellular senescence
Herranz, N., & Gil, J. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95148 · Cited by 1,232 · see citing works
Senescence and the SASP: many therapeutic avenues
Birch, J., & Gil, J. (2020) · Genes & Development · doi:10.1101/gad.343129.120 · Cited by 1,177 · see citing works
Self-citationCellular senescence: the good, the bad and the unknown
Huang, W., Hickson, L. J., Eirin, A., Kirkland, J. L., & Lerman, L. O. (2022) · Nature Reviews Nephrology · doi:10.1038/s41581-022-00601-z · Cited by 1,150 · see citing works
Mitochondrial dysfunction in cell senescence and aging
Miwa, S., Kashyap, S., Chini, E., & von Zglinicki, T. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158447 · Cited by 1,061 · see citing works
Self-citationCellular senescence drives age-dependent hepatic steatosis
Ogrodnik, M., Miwa, S., Tchkonia, T., Tiniakos, D., Wilson, C. L., Lahat, A., Day, C. P., Burt, A., Palmer, A., Anstee, Q. M., et al. (2017) · Nature Communications · doi:10.1038/ncomms15691 · Cited by 1,044 · see citing works
Self-citationPathogenic Mechanisms Underlying Idiopathic Pulmonary Fibrosis
Moss, B. J., Ryter, S. W., & Rosas, I. O. (2021) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-042320-030240 · Cited by 838 · see citing works
Regulation and metabolic functions of mTORC1 and mTORC2.
Szwed, A., Kim, E., & Jacinto, E. (2021) · Physiological Reviews · doi:10.1152/physrev.00026.2020 · Cited by 723 · see citing works
Telomere dysfunction in ageing and age-related diseases
Rossiello, F., Jurk, D., Passos, J. F., & d’Adda di Fagagna, F. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00842-x · Cited by 754 · see citing works
Self-citationThe metabolic roots of senescence: mechanisms and opportunities for intervention
Wiley, C. D., & Campisi, J. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00483-8 · Cited by 691 · see citing works
Apoptotic stress causes mtDNA release during senescence and drives the SASP
Victorelli, S. G., Salmonowicz, H., Chapman, J., Martini, H., Vizioli, M. G., Riley, J. S., Cloix, C., Hall-Younger, E., Espíndola‐Netto, J. M., Jurk, D., et al. (2023) · Nature · doi:10.1038/s41586-023-06621-4 · Cited by 696 · see citing works
Self-citationA guide to assessing cellular senescence <i>in vitro</i> and <i>in vivo</i>
González‐Gualda, E., Baker, A. G., Fruk, L., & Muñoz‐Espín, D. (2021) · The FEBS Journal · doi:10.1111/febs.15570 · Cited by 645 · see citing works
Mitochondrial signal transduction
Picard, M. A., & Shirihai, O. S. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.10.008 · Cited by 666 · see citing works
mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review
Weichhart, T. (2018) · Gerontology · doi:10.1159/000484629 · Cited by 596 · see citing works
Tau protein aggregation is associated with cellular senescence in the brain
Musi, N., Valentine, J. M., Sickora, K. R., Baeuerle, E., Thompson, C. S., Shen, Q., & Orr, M. E. (2018) · Aging Cell · doi:10.1111/acel.12840 · Cited by 595 · see citing works
The senescence-associated secretory phenotype and its regulation
Lopes-Paciencia, S., Saint-Germain, E., Rowell, M.-C., Ruiz, A. F., Kalegari, P., & Ferbeyre, G. (2019) · Cytokine · doi:10.1016/j.cyto.2019.01.013 · Cited by 601 · see citing works
Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis
Ogrodnik, M., Zhu, Y., Langhi, L. G. P., Tchkonia, T., Krüger, P., Fielder, E., Victorelli, S., Ruswhandi, R. A., Giorgadze, N., Pirtskhalava, T., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.12.008 · Cited by 536 · see citing works
Self-citationMookerjee, S. A., Gerencser, A. A., Nicholls, D. G., & Brand, M. D. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.774471 · Cited by 550 · see citing works
Length-independent telomere damage drives post-mitotic cardiomyocyte senescence
Anderson, R., Lagnado, A., Maggiorani, D., Walaszczyk, A., Dookun, E., Chapman, J., Birch, J., Salmonowicz, H., Ogrodnik, M., Jurk, D., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018100492 · Cited by 532 · see citing works
Self-citationMitochondrial fusion, fission, and mitochondrial toxicity
Meyer, J. N., Leuthner, T. C., & Luz, A. L. (2017) · Toxicology · doi:10.1016/j.tox.2017.07.019 · Cited by 521 · see citing works
Oxidative Stress in Neurodegenerative Diseases: From a Mitochondrial Point of View
Cenini, G., Lloret, A., & Cascella, R. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/2105607 · Cited by 435 · see citing works
Senescent cell clearance by the immune system: Emerging therapeutic opportunities
Prata, L. G. P. L., Ovsyannikova, I. G., Tchkonia, T., & Kirkland, J. L. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2019.04.003 · Cited by 497 · see citing works
From Ancient Pathways to Aging Cells—Connecting Metabolism and Cellular Senescence
Wiley, C. D., & Campisi, J. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.010 · Cited by 440 · see citing works
The role of retrotransposable elements in ageing and age-associated diseases
Gorbunova, V., Seluanov, A., Mita, P., McKerrow, W., Fenyö, D., Boeke, J. D., Linker, S. B., Gage, F. H., Kreiling, J. A., Petrashen, A. P., et al. (2021) · Nature · doi:10.1038/s41586-021-03542-y · Cited by 457 · see citing works
Ageing, Cellular Senescence and Neurodegenerative Disease
Kritsilis, M., V. Rizou, S., Koutsoudaki, P. N., Evangelou, K., Gorgoulis, V. G., & Papadopoulos, D. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19102937 · Cited by 448 · see citing works
mTOR as a central regulator of lifespan and aging
Papadopoli, D. J., Boulay, K., Kazak, L., Pollak, M., Mallette, F. A., Topisirović, I., & Hulea, L. (2019) · F1000Research · doi:10.12688/f1000research.17196.1 · Cited by 431 · see citing works
Telomeres and cell senescence—size matters not
Victorelli, S., & Passos, J. F. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.03.027 · Cited by 413 · see citing works
Self-citationOgrodnik, M., Evans, S. A., Fielder, E., Victorelli, S., Kruger, P., Salmonowicz, H., Weigand, B. M., Patel, A. D., Pirtskhalava, T., Inman, C. L., et al. (2021) · Aging Cell · doi:10.1111/acel.13296 · Cited by 405 · see citing works
Self-citationMitochondria in Cell Senescence: Is Mitophagy the Weakest Link?
Korolchuk, V. I., Miwa, S., Carroll, B., & von Zglinicki, T. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.03.020 · Cited by 409 · see citing works
“Indeed, in senescent cells activity of mTORC1 appears to be elevated (Correia-Melo et al., 2016; Dalle Pezze et al., 2014; Demidenko and Blagosklonny, 2008) and become unresponsive to starvation signals.”
BackgroundInfluentialSelf-citationMechanisms and Regulation of Cellular Senescence
Roger, L., Tomas, F., & Gire, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222313173 · Cited by 395 · see citing works
DNA damage-how and why we age?
Yousefzadeh, M., Henpita, C., Vyas, R., Soto-Palma, C., Robbins, P., & Niedernhofer, L. (2021) · eLife · doi:10.7554/elife.62852 · Cited by 399 · see citing works
Role of mitochondrial reactive oxygen species in homeostasis regulation
Zhang, B., Pan, C., Feng, C., Yan, C., Yu, Y., Chen, Z., Guo, C., & Wang, X. (2022) · Redox Report · doi:10.1080/13510002.2022.2046423 · Cited by 397 · see citing works
Vizioli, M. G., Liu, T., Miller, K. N., Robertson, N. A., Gilroy, K., Lagnado, A. B., Perez-Garcia, A., Kiourtis, C., Dasgupta, N., Lei, X., et al. (2020) · Genes & Development · doi:10.1101/gad.331272.119 · Cited by 359 · see citing works
Self-citationRapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism
Wang, R., Yu, Z., Sunchu, B., Shoaf, J., Dang, I., Zhao, S., Caples, K., Bradley, L., Beaver, L. M., Ho, E., et al. (2017) · Aging Cell · doi:10.1111/acel.12587 · Cited by 360 · see citing works
The role of mitochondrial <scp>ROS</scp> in the aging brain
Stefanatos, R., & Sanz, A. (2018) · FEBS Letters · doi:10.1002/1873-3468.12902 · Cited by 358 · see citing works
Cellular senescence: all roads lead to mitochondria
Martini, H., & Passos, J. F. (2023) · The FEBS Journal · doi:10.1111/febs.16361 · Cited by 334 · see citing works
Self-citationTherapy-Induced Senescence: Opportunities to Improve Anticancer Therapy
Prasanna, P. G. S., Citrin, D. E., Hildesheim, J., Ahmed, M. M., Venkatachalam, S., Riscuta, G., Xi, D., Zheng, G., van Deursen, J., Goronzy, J. J., et al. (2021) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djab064 · Cited by 351 · see citing works
Stress, cell senescence and organismal ageing
de Magalhães, J. P., & Passos, J. F. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.07.001 · Cited by 316 · see citing works
Self-citationTai, H., Wang, Z., Gong, H., Han, X., Zhou, J., Wang, X., Wei, X., Ding, Y., Huang, N., Qin, J., et al. (2017) · Autophagy · doi:10.1080/15548627.2016.1247143 · Cited by 334 · see citing works
Mitochondrial dysfunction and cell senescence: deciphering a complex relationship
Chapman, J., Fielder, E., & Passos, J. F. (2019) · FEBS Letters · doi:10.1002/1873-3468.13498 · Cited by 325 · see citing works
Self-citationMitochondrial DNA Release in Innate Immune Signaling
Newman, L. E., & Shadel, G. S. (2023) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-032620-104401 · Cited by 331 · see citing works
Skin Senescence: Mechanisms and Impact on Whole-Body Aging
Franco, A. C., Aveleira, C., & Cavadas, C. (2022) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2021.12.003 · Cited by 321 · see citing works
Psychological Stress and Mitochondria: A Conceptual Framework
Picard, M. A., & McEwen, B. S. (2018) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000544 · Cited by 318 · see citing works
Cytoplasmic DNA: sources, sensing, and role in aging and disease
Miller, K. N., Victorelli, S. G., Salmonowicz, H., Dasgupta, N., Liu, T., Passos, J. F., & Adams, P. D. (2021) · Cell · doi:10.1016/j.cell.2021.09.034 · Cited by 288 · see citing works
Self-citationCuollo, L., Antonangeli, F., Santoni, A., & Soriani, A. (2020) · Biology · doi:10.3390/biology9120485 · Cited by 291 · see citing works
A Senescence-Centric View of Aging: Implications for Longevity and Disease
Borghesan, M., Hoogaars, W. M. H., Varela-Eirin, M., Talma, N., & Demaria, M. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.07.002 · Cited by 267 · see citing works
Mechanisms and Functions of Spatial Protein Quality Control
Sontag, E. M., Samant, R. S., & Frydman, J. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014616 · Cited by 269 · see citing works
The senescent bystander effect is caused by ROS-activated NF-κB signalling
Nelson, G., Kucheryavenko, O., Wordsworth, J., & von Zglinicki, T. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.08.005 · Cited by 280 · see citing works
Self-citationThe Dual Role of Cellular Senescence in Developing Tumors and Their Response to Cancer Therapy
Schosserer, M., Grillari, J., & Breitenbach, M. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00278 · Cited by 261 · see citing works
Senescent human melanocytes drive skin ageing via paracrine telomere dysfunction
Victorelli, S., Lagnado, A., Halim, J., Moore, W., Talbot, D., Barrett, K., Chapman, J., Birch, J., Ogrodnik, M., Meves, A., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2019101982 · Cited by 258 · see citing works
Self-citationThe bystander effect contributes to the accumulation of senescent cells in vivo
da Silva, P. F. L., Ogrodnik, M., Kucheryavenko, O., Glibert, J., Miwa, S., Cameron, K., Ishaq, A., Saretzki, G., Nagaraja‐Grellscheid, S., Nelson, G., et al. (2019) · Aging Cell · doi:10.1111/acel.12848 · Cited by 247 · see citing works
Self-citationZhu, Y., Liu, X., Ding, X., Wang, F., & Geng, X. (2019) · Biogerontology · doi:10.1007/s10522-018-9769-1 · Cited by 255 · see citing works
Mitochondrial Homeostasis and Cellular Senescence
Vasileiou, P. V. S., Evangelou, K., Vlasis, K. G., Fildisis, G., Panayiotidis, M. I., Chronopoulos, E., Passias, P.-G., Kouloukoussa, M., Gorgoulis, V. G., & Havaki, S. (2019) · Cells · doi:10.3390/cells8070686 · Cited by 246 · see citing works
Zheng, Z., Bian, Y., Zhang, Y., Ren, G., & Li, G. (2020) · Cell Cycle · doi:10.1080/15384101.2020.1743911 · Cited by 248 · see citing works
Pathophysiology and mechanisms of primary sarcopenia (Review)
Nishikawa, H., Fukunishi, S., Asai, A., Yokohama, K., Nishiguchi, S., & Higuchi, K. (2021) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2021.4989 · Cited by 235 · see citing works
Mitochondria in the signaling pathways that control longevity and health span
Akbari, M., Kirkwood, T. B. L., & Bohr, V. A. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100940 · Cited by 232 · see citing works
Birch-Machin, M. A., & Bowman, A. (2016) · British Journal of Dermatology · doi:10.1111/bjd.14906 · Cited by 225 · see citing works
Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner
Lagnado, A., Leslie, J., Ruchaud‐Sparagano, M., Victorelli, S., Hirsova, P., Ogrodnik, M., Collins, A. L., Vizioli, M. G., Habiballa, L., Saretzki, G., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2020106048 · Cited by 211 · see citing works
Self-citationIske, J., Seyda, M., Heinbokel, T., Maenosono, R., Minami, K., Nian, Y., Quante, M., Falk, C. S., Azuma, H., Martin, F., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18039-x · Cited by 211 · see citing works
Self-citationSenolytics and senostatics as adjuvant tumour therapy
Short, S. C., Fielder, E., Miwa, S., & von Zglinicki, T. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.01.056 · Cited by 201 · see citing works
Self-citationCellular Senescence in Postmitotic Cells: Beyond Growth Arrest
Sapieha, P., & Mallette, F. A. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.03.003 · Cited by 193 · see citing works
Roles of extracellular vesicles in the aging microenvironment and age‐related diseases
Yin, Y., Chen, H., Wang, Y., Zhang, L., & Wang, X. (2021) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12154 · Cited by 196 · see citing works
Senescent Cells: Emerging Targets for Human Aging and Age-Related Diseases
Song, S., Lam, E. W.-F., Tchkonia, T., Kirkland, J. L., & Sun, Y. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.03.008 · Cited by 195 · see citing works
“Although mitophagy in senescent cells appears to suppress the SASP [54], inhibition of the ETC can induce cellular senescence with a distinct SASP that lacks several key proinflammatory factors such as IL-6 and IL-8 [57].”
BackgroundCarroll, B., Nelson, G., Rabanal‐Ruiz, Y., Kucheryavenko, O., Dunhill-Turner, N. A., Chesterman, C. C., Zahari, Q., Zhang, T., Conduit, S. E., Mitchell, C. A., et al. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201610113 · Cited by 185 · see citing works
Self-citationLipid (per) oxidation in mitochondria: an emerging target in the ageing process?
Ademowo, O. S., Dias, H. K. I., Burton, D. G. A., & Griffiths, H. R. (2017) · Biogerontology · doi:10.1007/s10522-017-9710-z · Cited by 184 · see citing works
Ogrodnik, M., Salmonowicz, H., & Gladyshev, V. N. (2019) · Aging Cell · doi:10.1111/acel.12841 · Cited by 184 · see citing works
Senescence as a therapeutic target in cancer and age-related diseases
McHugh, D., Durán, I., & Gil, J. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01074-4 · Cited by 199 · see citing works
Metabolic landscape in cardiac aging: insights into molecular biology and therapeutic implications
Xie, S., Xu, S., Deng, W., & Tang, Q. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01378-8 · Cited by 185 · see citing works
Regulation of Survival Networks in Senescent Cells: From Mechanisms to Interventions
Soto-Gamez, A., Quax, W. J., & Demaria, M. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.05.036 · Cited by 175 · see citing works
Gao, X., Yu, X., Zhang, C., Wang, Y., Sun, Y., Sun, H., Zhang, H., Shi, Y., & He, X. (2022) · Stem Cell Reviews and Reports · doi:10.1007/s12015-022-10370-8 · Cited by 180 · see citing works
Teissier, T., & Boulanger, É. (2019) · Biogerontology · doi:10.1007/s10522-019-09808-3 · Cited by 177 · see citing works
Anti-senescence compounds: A potential nutraceutical approach to healthy aging
Gurău, F., Baldoni, S., Prattichizzo, F., Espinosa, E., Amenta, F., Procopio, A. D., Albertini, M. C., Bonafè, M., & Olivieri, F. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.05.001 · Cited by 179 · see citing works
The Metabolic Impact on Histone Acetylation and Transcription in Ageing
Peleg, S., Feller, C., Ladurner, A. G., & Imhof, A. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.05.008 · Cited by 178 · see citing works
Kawamura, K., Qi, F., & Kobayashi, J. (2018) · Journal of Radiation Research · doi:10.1093/jrr/rrx091 · Cited by 176 · see citing works
mTORC1 and Nutrient Homeostasis: The Central Role of the Lysosome
Rabanal-Ruiz, Y., & Korolchuk, V. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030818 · Cited by 159 · see citing works
Self-citationCellular Senescence: Molecular Targets, Biomarkers, and Senolytic Drugs
Kudlová, N., Sanctis, J. B. D., & Hajdúch, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084168 · Cited by 176 · see citing works
Senescence in Post-Mitotic Cells: A Driver of Aging?
von Zglinicki, T., Wan, T., & Miwa, S. (2021) · Antioxidants & Redox Signaling · doi:10.1089/ars.2020.8048 · Cited by 170 · see citing works
Self-citationMitochondria, telomeres and cell senescence: Implications for lung ageing and disease
Birch, J., Barnes, P. J., & Passos, J. F. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.10.005 · Cited by 173 · see citing works
Self-citationMitochondrial mass governs the extent of human T cell senescence
Callender, L. A., Carroll, E. C., Bober, E., Akbar, A. N., Solito, E., & Henson, S. M. (2019) · Aging Cell · doi:10.1111/acel.13067 · Cited by 167 · see citing works
Where Metabolism Meets Senescence: Focus on Endothelial Cells
Sabbatinelli, J., Prattichizzo, F., Olivieri, F., Procopio, A. D., Rippo, M. R., & Giuliani, A. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01523 · Cited by 168 · see citing works
Cellular Senescence: From Mechanisms to Current Biomarkers and Senotherapies
Lucas, V., Cavadas, C., & Aveleira, C. A. (2023) · Pharmacological Reviews · doi:10.1124/pharmrev.122.000622 · Cited by 169 · see citing works
Fibroblast senescence in the pathology of idiopathic pulmonary fibrosis
Waters, D. W., Blokland, K. E. C., Pathinayake, P. S., Burgess, J. K., Mutsaers, S. E., Prêle, C. M., Schuliga, M. J., Grainge, C., & Knight, D. A. (2018) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00037.2018 · Cited by 167 · see citing works
Kandhaya-Pillai, R., Miro-Mur, F., Alijotas-Reig, J., Tchkonia, T., Kirkland, J. L., & Schwartz, S. (2017) · Aging · doi:10.18632/aging.101328 · Cited by 165 · see citing works
Molecular Mechanisms of Neuroinflammation in Aging and Alzheimer’s Disease Progression
Andronie-Cioară, F. L., Ardelean, A. I., Nistor-Cseppento, C. D., Jurcău, A., Jurcău, M. C., Pașcalău, N., & Marcu, F. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24031869 · Cited by 164 · see citing works
Mitochondrial dysfunction in the regulation of aging and aging-related diseases
Zhang, X., Gao, Y., Zhang, S., Wang, Y., Pei, X., Chen, Y., Zhang, J., Zhang, Y., Du, Y., Hao, S., et al. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02308-7 · Cited by 175 · see citing works
Senescence and senotherapeutics: a new field in cancer therapy
Myrianthopoulos, V., Evangelou, K., Vasileiou, P. V. S., Cooks, T., Vassilakopoulos, T. P., Pangalis, G. A., Kouloukoussa, M., Kittas, C., Georgakilas, A. G., & Gorgoulis, V. G. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.08.006 · Cited by 160 · see citing works
Faces of cellular senescence in skin aging
Ho, C. Y., & Dreesen, O. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111525 · Cited by 164 · see citing works
Liu, T., Yang, Q., Zhang, X., Qin, R., Shan, W., Zhang, H., & Chen, X. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118116 · Cited by 158 · 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
mTORC1 pathway in DNA damage response.
Ma, Y.-X., Vassetzky, Y., & Dokudovskaya, S. (2018) · Biochimica et biophysica acta. Molecular cell research · doi:10.1016/j.bbamcr.2018.06.011 · Cited by 42 · see citing works
Mitochondria initiate and regulate sarcopenia
Alway, S. E., Mohamed, J. S., & Myers, M. J. (2017) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000101 · Cited by 153 · see citing works
“Mitochondrial stress in aging can originate from greater levels of oxidants, DNA damage, or denervation (31,133).”
BackgroundSarcopenia and Its Implications for Metabolic Health
Hunter, G. R., Singh, H., Carter, S. J., Bryan, D. R., & Fisher, G. (2019) · Journal of Obesity · doi:10.1155/2019/8031705 · Cited by 153 · see citing works
The Impact of HIV- and ART-Induced Mitochondrial Dysfunction in Cellular Senescence and Aging
Schank, M., Zhao, J., Moorman, J. P., & Yao, Z. Q. (2021) · Cells · doi:10.3390/cells10010174 · Cited by 151 · see citing works
The multifaceted role of the SASP in atherosclerosis: from mechanisms to therapeutic opportunities
Sun, Y., Wang, X., Liu, T., Zhu, X., & Pan, X. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00815-5 · Cited by 151 · see citing works
Aging and Caloric Restriction Research: A Biological Perspective with Translational Potential
Balasubramanian, P., Howell, P. R., & Anderson, R. M. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.06.015 · Cited by 148 · see citing works
Self-citationSIRT4 interacts with OPA1 and regulates mitochondrial quality control and mitophagy
Lang, A., Anand, R., Altinoluk-Hambüchen, S., Ezzahoini, H., Stefanski, A., Iram, A., Bergmann, L., Urbach, J., Böhler, P., Hänsel, J., et al. (2017) · Aging · doi:10.18632/aging.101307 · Cited by 145 · see citing works
Summer, R. S., Shaghaghi, H., Schriner, D., Roque, W., Sales, D., Cuevas-Mora, K., Desai, V. S., Bhushan, A., Ramirez, M. I., & Romero, F. (2019) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00244.2018 · Cited by 145 · see citing works
- Authors
- Correia‐Melo, C., Marques, F. D., Anderson, R., Hewitt, G., Hewitt, R., Cole, J., Carroll, B. M., Miwa, S., Birch, J., Merz, A., Rushton, M. D., Charles, M., Jurk, D., Tait, S. W., Czapiewski, R., Greaves, L., Nelson, G., Bohlooly‐Y, M., Rodriguez‐Cuenca, S., Vidal‐Puig, A., Mann, D., Saretzki, G., Quarato, G., Green, D. R., Adams, P. D., von Zglinicki, T., Korolchuk, V. I., & Passos, J. F.
- Affiliations
- Universidade do Porto (PT)
- Newcastle University (GB)
- Cancer Research UK Scotland Institute (GB)
- Wellcome Centre for Mitochondrial Research (GB)
- AstraZeneca (Sweden) (SE)
- University of Cambridge (GB)
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Passos, João F
- ORCID
- Correia‐Melo, Clara
- Hewitt, Graeme
- Cole, John
- Carroll, Bernadette M
- Miwa, Satomi
- Birch, Jodie
- Charles, Michelle
- Jurk, Diana
- Tait, Stephen WG
- Czapiewski, Rafal
- Greaves, Laura
- Nelson, Glyn
- Bohlooly‐Y, Mohammad
- Vidal‐Puig, Antonio
- Mann, Derek
- Saretzki, Gabriele
- Quarato, Giovanni
- Green, Douglas R
- Adams, Peter D
- Korolchuk, Viktor I
- Passos, João F
- Venue
- The EMBO Journal
- Published
- 2016-02-04
- Volume
- 35
- Issue
- 7
- Pages
- 724-742
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC4818766
- OpenAlex
- W2267737556
- Cited by
- 796
- References
- 66
- Citations by year
- 2026: 71 · 2025: 104 · 2024: 91 · 2023: 83 · 2022: 82 · 2021: 92 · 2020: 74 · 2019: 59 · 2018: 66 · 2017: 48 · 2016: 25
- FWCI
- 53.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The EMBO Journal (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Explore Bristol Research (publishedVersion, cc-by)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Bristol Research (University of Bristol) (submittedVersion, cc-by)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- FP7‐MITIN (HEALTH‐F4‐2008‐223450)
- Medical Research Council Centre for Obesity and Related Metabolic Diseases
- BBSRC (BB/I020748/1, BB/K019260/1, BB/H022384/1, BB/K017314/1)
- Royal Society University Fellowship
- Foundation for Science and Technology (FCT), Portugal
- GABBA Program
- University of Porto
- Newcastle University
- David Phillips Fellowship
- AstraZeneca
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- cellular senescence, mitochondria, aging, pro-inflammatory phenotype, mitochondrial biogenesis, PGC-1β, mTORC1, ATM, Akt, DNA damage response, reactive oxygen species, glycolysis, cell cycle arrest, transcriptomics
- MeSH terms
- Aging, Animals, Cell Line, Humans, Mitochondria, Models, Biological, Phenotype, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
