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Journal ArticleDOI

To stay young, kill zombie cells

26 Oct 2017-Nature (Nature)-Vol. 550, Iss: 7677, pp 448-450
TL;DR: Killing off cells that refuse to die on their own has proved a powerful anti-ageing strategy in mice as mentioned in this paper, and it has been successfully applied to humans as well.
Abstract: Killing off cells that refuse to die on their own has proved a powerful anti-ageing strategy in mice. Now it's about to be tested in humans.

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Citations
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Journal ArticleDOI
TL;DR: The beneficial effects of polyphenol-rich foods in relation to the Mediterranean diet and the dietary habits of long-lived individuals are discussed, and their ability to modulate bacterial genera in the gut is examined.

126 citations

Journal ArticleDOI
16 May 2018-Nature
TL;DR: New therapeutic approaches aim to harness cell plasticity for tissue repair and regeneration while avoiding the risk of malignant transformation of cells.
Abstract: Mammalian organs comprise an extraordinary diversity of cell and tissue types. Regenerative organs, such as the skin and gastrointestinal tract, use resident stem cells to maintain tissue function. Organs with a lower cellular turnover, such as the liver and lungs, mostly rely on proliferation of committed progenitor cells. In many organs, injury reveals the plasticity of both resident stem cells and differentiated cells. The ability of resident cells to maintain and repair organs diminishes with age, whereas, paradoxically, the risk of cancer increases. New therapeutic approaches aim to harness cell plasticity for tissue repair and regeneration while avoiding the risk of malignant transformation of cells.

120 citations

Journal ArticleDOI
TL;DR: Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy Center of Clinical Pathology and Innovative Therapy, INRCA-IRCCS National Institute, AnCONA, Italy IRCCS MultiMedica, Milan, Italy.
Abstract: Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy Center of Clinical Pathology and Innovative Therapy, INRCA-IRCCS National Institute, Ancona, Italy IRCCS MultiMedica, Milan, Italy University of Natural Resources and Life Sciences Vienna, Vienna, Austria Department of Pathobiology and Medical Biotechnologies, University of Palermo, Corso Tukory 211, 90134 Palermo, Italy

103 citations


Cites background from "To stay young, kill zombie cells"

  • ...The discoverers of senolytics have announced their intention to test these molecules in humans in specific setting in the next future [37]....

    [...]

Journal ArticleDOI
TL;DR: The roles of extrinsic and intrinsic factors in cardiac ageing are discussed, including environment, lifestyle, genetics and epigenetics, inflammation, and oxidative stress, and how they might be therapeutically targeted.
Abstract: Cardiac ageing manifests as a decline in function leading to heart failure. At the cellular level, ageing entails decreased replicative capacity and dysregulation of cellular processes in myocardial and nonmyocyte cells. Various extrinsic parameters, such as lifestyle and environment, integrate important signalling pathways, such as those involving inflammation and oxidative stress, with intrinsic molecular mechanisms underlying resistance versus progression to cellular senescence. Mitigation of cardiac functional decline in an ageing organism requires the activation of enhanced maintenance and reparative capacity, thereby overcoming inherent endogenous limitations to retaining a youthful phenotype. Deciphering the molecular mechanisms underlying dysregulation of cellular function and renewal reveals potential interventional targets to attenuate degenerative processes at the cellular and systemic levels to improve quality of life for our ageing population. In this Review, we discuss the roles of extrinsic and intrinsic factors in cardiac ageing. Animal models of cardiac ageing are summarized, followed by an overview of the current and possible future treatments to mitigate the deleterious effects of cardiac ageing.

97 citations

Journal ArticleDOI
21 Feb 2020
TL;DR: The present review will focus on current scientific knowledge about MSC aging mechanisms, control and effects, including possible anti-aging treatments.
Abstract: Mesenchymal stem/stromal cells (MSCs) are a reservoir for tissue homeostasis and repair that age during organismal aging. Beside the fundamental in vivo role of MSCs, they have also emerged in the last years as extremely promising therapeutic agents for a wide variety of clinical conditions. MSC use frequently requires in vitro expansion, thus exposing cells to replicative senescence. Aging of MSCs (both in vivo and in vitro) can affect not only their replicative potential, but also their properties, like immunomodulation and secretory profile, thus possibly compromising their therapeutic effect. It is therefore of critical importance to unveil the underlying mechanisms of MSC senescence and to define shared methods to assess MSC aging status. The present review will focus on current scientific knowledge about MSC aging mechanisms, control and effects, including possible anti-aging treatments.

65 citations


Cites background from "To stay young, kill zombie cells"

  • ...Recent evidences showed that genetic and pharmacological elimination of senescent cells in animal models can extend lifespan and delay the onset of age-related pathologies [207]....

    [...]

References
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Journal ArticleDOI
TL;DR: A cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment is suggested.
Abstract: Cellular senescence suppresses cancer by arresting cell proliferation, essentially permanently, in response to oncogenic stimuli, including genotoxic stress. We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells. We show that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy. This senescence-associated secretory phenotype (SASP) developed slowly over several days and only after DNA damage of sufficient magnitude to induce senescence. Remarkably similar SASPs developed in normal fibroblasts, normal epithelial cells, and epithelial tumor cells after genotoxic stress in culture, and in epithelial tumor cells in vivo after treatment of prostate cancer patients with DNA-damaging chemotherapy. In cultured premalignant epithelial cells, SASPs induced an epithelial-mesenchyme transition and invasiveness, hallmarks of malignancy, by a paracrine mechanism that depended largely on the SASP factors interleukin (IL)-6 and IL-8. Strikingly, two manipulations markedly amplified, and accelerated development of, the SASPs: oncogenic RAS expression, which causes genotoxic stress and senescence in normal cells, and functional loss of the p53 tumor suppressor protein. Both loss of p53 and gain of oncogenic RAS also exacerbated the promalignant paracrine activities of the SASPs. Our findings define a central feature of genotoxic stress-induced senescence. Moreover, they suggest a cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment.

2,923 citations

Journal ArticleDOI
10 Nov 2011-Nature
TL;DR: Data indicate that cellular senescence is causally implicated in generating age-related phenotypes and that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan.
Abstract: Advanced age is the main risk factor for most chronic diseases and functional deficits in humans, but the fundamental mechanisms that drive ageing remain largely unknown, impeding the development of interventions that might delay or prevent age-related disorders and maximize healthy lifespan. Cellular senescence, which halts the proliferation of damaged or dysfunctional cells, is an important mechanism to constrain the malignant progression of tumour cells. Senescent cells accumulate in various tissues and organs with ageing and have been hypothesized to disrupt tissue structure and function because of the components they secrete. However, whether senescent cells are causally implicated in age-related dysfunction and whether their removal is beneficial has remained unknown. To address these fundamental questions, we made use of a biomarker for senescence, p16(Ink4a), to design a novel transgene, INK-ATTAC, for inducible elimination of p16(Ink4a)-positive senescent cells upon administration of a drug. Here we show that in the BubR1 progeroid mouse background, INK-ATTAC removes p16(Ink4a)-positive senescent cells upon drug treatment. In tissues--such as adipose tissue, skeletal muscle and eye--in which p16(Ink4a) contributes to the acquisition of age-related pathologies, life-long removal of p16(Ink4a)-expressing cells delayed onset of these phenotypes. Furthermore, late-life clearance attenuated progression of already established age-related disorders. These data indicate that cellular senescence is causally implicated in generating age-related phenotypes and that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan.

2,738 citations

Journal ArticleDOI
11 Feb 2016-Nature
TL;DR: It is shown that compared to vehicle alone, AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds and the clearance of p16Ink4a-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs without apparent side effects.
Abstract: Cellular senescence, a stress-induced irreversible growth arrest often characterized by expression of p16(Ink4a) (encoded by the Ink4a/Arf locus, also known as Cdkn2a) and a distinctive secretory phenotype, prevents the proliferation of preneoplastic cells and has beneficial roles in tissue remodelling during embryogenesis and wound healing. Senescent cells accumulate in various tissues and organs over time, and have been speculated to have a role in ageing. To explore the physiological relevance and consequences of naturally occurring senescent cells, here we use a previously established transgene, INK-ATTAC, to induce apoptosis in p16(Ink4a)-expressing cells of wild-type mice by injection of AP20187 twice a week starting at one year of age. We show that compared to vehicle alone, AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. The clearance of p16(Ink4a)-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs without apparent side effects, including kidney, heart and fat, where clearance preserved the functionality of glomeruli, cardio-protective KATP channels and adipocytes, respectively. Thus, p16(Ink4a)-positive cells that accumulate during adulthood negatively influence lifespan and promote age-dependent changes in several organs, and their therapeutic removal may be an attractive approach to extend healthy lifespan.

1,882 citations

Journal ArticleDOI
13 Jun 2008-Cell
TL;DR: A model is proposed in which the context-dependent cytostatic and promitogenic functions of specific interleukins contribute to connect senescence with an inflammatory phenotype and cancer.

1,693 citations

Journal ArticleDOI
13 Jun 2008-Cell
TL;DR: It is reported that knocking down the chemokine receptor CXCR2 (IL8RB) alleviates both replicative and oncogene-induced senescence (OIS) and diminishes the DNA-damage response and suggests that senescent cells activate a self-amplifying secretory network in which CX CR2-binding chemokines reinforce growth arrest.

1,465 citations

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What to do to not age?

The paper discusses the potential anti-aging strategy of killing off senescent cells, but it does not provide specific recommendations on what individuals can do to prevent aging.

What s the best way to stay young?

The paper discusses the strategy of killing off senescent cells as a powerful anti-aging approach in mice. However, it does not provide information on the best way to stay young.