Therapy-Induced Senescence: An “Old” Friend Becomes the Enemy DOI Open Access
Tareq Saleh, Sarah Bloukh,

Valerie J. Carpenter

et al.

Cancers, Journal Year: 2020, Volume and Issue: 12(4), P. 822 - 822

Published: March 29, 2020

For the past two decades, cellular senescence has been recognized as a central component of tumor cell response to chemotherapy and radiation. Traditionally, this form senescence, termed Therapy-Induced Senescence (TIS), was linked extensive nuclear damage precipitated by classical genotoxic chemotherapy. However, number other forms therapy have also shown induce in cells independently direct genomic damage. This review attempts provide comprehensive summary both conventional targeted anticancer therapeutics that vitro vivo. Still, utility promoting therapeutic endpoint remains under debate. Since represents durable growth arrest, it might be argued is desirable outcome cancer therapy. accumulating evidence suggesting capacity escape from TIS would support an alternative conclusion, provides avenue whereby can evade potentially lethal action drugs, allowing enter temporary state dormancy eventually facilitates disease recurrence, often more aggressive state. Furthermore, now strongly connected remodeling, dormancy, acquiring ominous malignant phenotypes accounts for several untoward adverse effects Here, we argue barrier effective treatment, discuss emerging efforts identify exploit agents with senolytic properties strategy elimination persistent residual surviving population, goal mitigating tumor-promoting influence senescent thereby reduce likelihood relapse.

Language: Английский

Mitochondrial dysfunction and cell senescence: deciphering a complex relationship DOI Open Access
James Chapman, Edward Fielder, João F. Passos

et al.

FEBS Letters, Journal Year: 2019, Volume and Issue: 593(13), P. 1566 - 1579

Published: June 18, 2019

Cellular senescence and mitochondrial dysfunction have both been defined as classical hallmarks of the ageing process. Here, we review intricate relationship between two. In context ageing, it is now well regarded that cellular a key driver in onset number age‐related pathologies. Emerging evidence has pinpointed mitochondria one modulators development phenotype, particularly pro‐inflammatory associated secretory phenotype (SASP). This focuses on contribution homeostatic mechanisms, reactive oxygen species metabolites programme. Furthermore, discuss emerging pathways mitochondrial‐mediated mechanisms may be influencing SASP and, subsequently, explore how these exploited to open up new therapeutic avenues.

Language: Английский

Citations

261
Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice DOI Creative Commons
Emanuel J. Novais,

Victoria A. Tran,

Shira N. Johnston

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 3, 2021

Intervertebral disc degeneration is highly prevalent within the elderly population and a leading cause of chronic back pain disability. Due to link between senescence, we explored ability Dasatinib Quercetin drug combination (D + Q) prevent an age-dependent progression in mice. We treated C57BL/6 mice beginning at 6, 14, 18 months age, analyzed them 23 age. Interestingly, 6- 14-month D Q cohorts show lower incidences degeneration, treatment results significant decrease senescence markers p16INK4a, p19ARF, SASP molecules IL-6 MMP13. Treatment also preserves cell viability, phenotype, matrix content. Although transcriptomic analysis shows compartment-specific effects treatment, death cytokine response pathways are commonly modulated across tissue types. Results suggest that senolytics may provide attractive strategy mitigating degeneration.

Language: Английский

Citations

257
Cellular senescence: at the nexus between ageing and diabetes DOI Creative Commons
Allyson K. Palmer,

Birgit Gustafson,

James L. Kirkland

et al.

Diabetologia, Journal Year: 2019, Volume and Issue: 62(10), P. 1835 - 1841

Published: Aug. 26, 2019

Ageing and diabetes lead to similar organ dysfunction that is driven by parallel molecular mechanisms, one of which cellular senescence. The abundance senescent cells in various tissues increases with age, obesity diabetes. Senescent have been directly implicated the generation insulin resistance. Recently, drugs preferentially target cells, known as senolytics, described recently entered clinical trials. In this review, we explore biological links between ageing diabetes, specifically focusing on We summarise current data senescence key associated development phenotypes type 2 discuss therapeutic potential targeting

Language: Английский

Citations

251
Enhancing myelin renewal reverses cognitive dysfunction in a murine model of Alzheimer’s disease DOI Creative Commons

Jing‐Fei Chen,

Kun Liu, Bo Hu

et al.

Neuron, Journal Year: 2021, Volume and Issue: 109(14), P. 2292 - 2307.e5

Published: June 7, 2021

Language: Английский

Citations

243
Therapy-Induced Senescence: An “Old” Friend Becomes the Enemy DOI Open Access
Tareq Saleh, Sarah Bloukh,

Valerie J. Carpenter

et al.

Cancers, Journal Year: 2020, Volume and Issue: 12(4), P. 822 - 822

Published: March 29, 2020

For the past two decades, cellular senescence has been recognized as a central component of tumor cell response to chemotherapy and radiation. Traditionally, this form senescence, termed Therapy-Induced Senescence (TIS), was linked extensive nuclear damage precipitated by classical genotoxic chemotherapy. However, number other forms therapy have also shown induce in cells independently direct genomic damage. This review attempts provide comprehensive summary both conventional targeted anticancer therapeutics that vitro vivo. Still, utility promoting therapeutic endpoint remains under debate. Since represents durable growth arrest, it might be argued is desirable outcome cancer therapy. accumulating evidence suggesting capacity escape from TIS would support an alternative conclusion, provides avenue whereby can evade potentially lethal action drugs, allowing enter temporary state dormancy eventually facilitates disease recurrence, often more aggressive state. Furthermore, now strongly connected remodeling, dormancy, acquiring ominous malignant phenotypes accounts for several untoward adverse effects Here, we argue barrier effective treatment, discuss emerging efforts identify exploit agents with senolytic properties strategy elimination persistent residual surviving population, goal mitigating tumor-promoting influence senescent thereby reduce likelihood relapse.

Language: Английский

Citations

227