Rapamycin and the inhibition of the secretory phenotype

@article{Wang2017RapamycinAT,
  title={Rapamycin and the inhibition of the secretory phenotype},
  author={R. Wang and B. Sunchu and V. P{\'e}rez},
  journal={Experimental Gerontology},
  year={2017},
  volume={94},
  pages={89-92}
}
Senescent cells contribute to age-related pathology and loss of function, and their selective removal improves physiological function and extends longevity. Cell senescence is a complex process that can be triggered by multiple challenges. Recently it has been observed that the composition of the secretory phenotype or SASP depends on the insult that triggers cell senescence. Rapamycin, an inhibitor of mTOR that increases longevity in several species, inhibits cell senescence in vitro, while… Expand
Senescence in the aging process
TLDR
The aim is to gain a better understanding of how the senescent cell phenotype varies between different individuals and tissues, discover how senescence predisposes to organismal frailty, and develop mechanisms by which the deleterious effects of senescent cells can be ameliorated. Expand
Rapamycin promotes endothelial–mesenchymal transition during stress-induced premature senescence through the activation of autophagy
TLDR
It is revealed that although rapamycin functions to inhibit senescence and suppress SASP in HCAECs undergoing SIPS, EndMT is induced due to the activation of autophagy, which led to activation of the TGF-β pathway, contributed to EndMT induction. Expand
Optimisation of a screening platform for determining IL-6 inflammatory signalling in the senescence-associated secretory phenotype (SASP)
TLDR
This paper describes optimisation and validation of a cell-based biosensor HEK cell line for measurement of IL-6 concentrations within the range secreted into conditioned medium by primary senescent fibroblasts, adapted for a 384 well plate format suitable for library screening applications. Expand
Senolytics in Disease, Ageing and Longevity
Cellular senescence is a hallmark of aging because senescent cells (SnCs) accumulate with age and play a causative role in many age-related diseases. Selectively eliminating SnCs has been emerging asExpand
Rapamycin retards epigenetic ageing of keratinocytes independently of its effects on replicative senescence, proliferation and differentiation
TLDR
It is reported here that epigenetic ageing is not affected by replicative senescence, telomere length, somatic cell differentiation, cellular proliferation rate or frequency and is instead retarded by rapamycin, the potent inhibitor of the mTOR complex which governs many pathways relating to cellular metabolism. Expand
Targeted Senolytic Strategies Based on the Senescent Surfaceome
TLDR
The ongoing efforts to design targeted senolytics are discussed, with special focus on the utilization of the extracellular epitopes displayed by the senescent surfaceome, and the avenues of research that have shown the most promising results so far are summarized. Expand
Immunosenescence: a key player in cancer development
TLDR
The characteristics of immunosenescence and its impact on malignant tumors and immunotherapy are highlighted, especially the future directions of tumor treatment through senescence-focused strategies. Expand
Anti-aging: senolytics or gerostatics (unconventional view)
Senolytics are basically anti-cancer drugs, repurposed to kill senescent cells selectively. It is even more difficult to selectively kill senescent cells than to kill cancer cells. Based on lessonsExpand
The quest to slow ageing through drug discovery
TLDR
The most promising interventions to slow ageing are examined and group them into two tiers based on the robustness of the preclinical, and some clinical, results, in which the top tier includes rapamycin, senolytics, metformin, acarbose, spermidine, NAD + enhancers and lithium. Expand
TOR inhibitors: from mammalian outcomes to pharmacogenetics in plants and algae.
TLDR
This review discusses the use of rapamycin and asTORis in plants and algae and concludes with guidelines for physiological studies and genetic screens with TOR inhibitors. Expand
...
1
2
...

References

SHOWING 1-10 OF 34 REFERENCES
mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype
TLDR
A mechanism by which mTOR controls the SASP is reported by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1. Expand
MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation
TLDR
It is shown that rapamycin selectively blunts the pro-inflammatory phenotype of senescent cells, which might ameliorate age-related pathologies, including late-life cancer, by suppressing senescence-associated inflammation. Expand
Rapamycin decelerates cellular senescence
TLDR
It is demonstrated that the duration of cell cycle arrest determines a progressive loss of proliferative capacity, and the data demonstrate that senescence can be pharmacologically suppressed. Expand
The senescence-associated secretory phenotype: the dark side of tumor suppression.
TLDR
A senescence-associated secretory phenotype (SASP) is acquired that turns senescent fibroblasts into proinflammatory cells that have the ability to promote tumor progression. Expand
Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype.
TLDR
It is shown that several manipulations that compromise mitochondrial function in proliferating human cells induce a senescence growth arrest with a modified SASP that lacks the IL-1-dependent inflammatory arm, providing a mechanism by which mitochondrial dysfunction can drive aging phenotypes. Expand
An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA.
TLDR
It is shown that senescent fibroblasts and endothelial cells appear very early in response to a cutaneous wound, where they accelerate wound closure by inducing myofibroblast differentiation through the secretion of platelet-derived growth factor AA (PDGF-AA). Expand
Senescence associated secretory phenotype profile from primary lung mice fibroblasts depends on the senescence induction stimuli
TLDR
The results showed important variations in the 62 cytokines analyzed, while SIPS and RS showed an increase in the secretion of most cytokines, and in PIIPS only 13 were incremented, suggesting that the senescence induction pathway might encompass dissimilar responses in adjacent cells and promote different outcomes. Expand
Cellular Senescence in Cancer and Aging
Cellular senescence, a state of irreversible growth arrest, can be triggered by multiple mechanisms including telomere shortening, the epigenetic derepression of the INK4a/ARF locus, and DNA damage.Expand
Aging, cellular senescence, and cancer.
  • J. Campisi
  • Biology, Medicine
  • Annual review of physiology
  • 2013
TLDR
The idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence is discussed. Expand
p38MAPK is a novel DNA damage response‐independent regulator of the senescence‐associated secretory phenotype
TLDR
It is shown that diverse senescence‐inducing stimuli activate the stress‐inducible kinase p38MAPK in normal human fibroblasts and assign p38 MAPK a novel role in SASP regulation—one that is necessary, sufficient, and independent of previously described pathways. Expand
...
1
2
3
4
...