Senescence suppressors: their practical importance in replicative lifespan extension in stem cells

2014 ◽  
Vol 71 (21) ◽  
pp. 4207-4219 ◽  
Author(s):  
Eun Seong Hwang
Keyword(s):  
Stem Cells ◽  
Practical Importance ◽  
Lifespan Extension ◽  
Replicative Lifespan

scholarly journals Circadian Regulation of Mitochondrial Uncoupling and Lifespan

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 740-741
Author(s):  
Matthew Ulgherait
Keyword(s):  
Stem Cells ◽  
Circadian Rhythm ◽  
Uncoupling Protein ◽  
Intestinal Stem Cells ◽  
Intestinal Stem Cell ◽  
Cellular Respiration ◽  
Circadian Regulation ◽  
Lifespan Extension ◽  
Diet Restriction ◽  
Mitochondrial Uncoupling

Abstract Because old age is associated with defects in circadian rhythm, loss of circadian regulation is thought to be pathogenic and contribute to mortality. We show instead that loss of specific circadian clock components Period (Per) and Timeless (Tim) in male Drosophila significantly extends lifespan. This lifespan extension is not mediated by canonical diet-restriction longevity pathways, but is due to altered cellular respiration via increased mitochondrial uncoupling. Lifespan extension of per mutants depends on mitochondrial uncoupling in the intestine. Moreover, up-regulated uncoupling protein UCP4C in intestinal stem cells and enteroblasts is sufficient to extend lifespan and preserve proliferative homeostasis in the gut with age. Consistent with inducing a metabolic state that prevents over-proliferation, mitochondrial uncoupling drugs also extend lifespan and inhibit intestinal stem cell overproliferation due to aging or even tumorigenesis. These results demonstrate that circadian-regulated intestinal mitochondrial uncoupling controls longevity in Drosophila and suggest a new potential anti-aging therapeutic target.

2. Embryonic stem cells

2021 ◽  
pp. 21-37
Author(s):  
Jonathan Slack
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Inner Cell Mass ◽  
Es Cells ◽  
Practical Importance ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Human Embryos ◽  
Mouse Es Cells ◽  
Stage Embryo

‘Embryonic stem cells’ focuses on embryonic stem (ES) cells, which are grown in tissue culture from the inner cell mass of a mammalian blastocyst-stage embryo. Human ES cells offer a potential route to making the kinds of cells needed for cell therapy. ES cells were originally prepared from mouse embryos. Although somewhat different, cells grown from inner cell masses of human embryos share many properties with mouse ES cells, such as being able to grow without limit and to generate differentiated cell types. Mouse ES cells have so far been of greater practical importance than those of humans because they have enabled a substantial research industry based on the creation of genetically modified mice.

scholarly journals Saccharomyces cerevisiae displays an increased growth rate and an extended replicative lifespan when grown under respiratory conditions in the presence of bacteria

2017 ◽  
Vol 63 (9) ◽  
pp. 806-810
Author(s):  
Paul A. Kirchman ◽  
Nicholas Van Zee
Keyword(s):  
Escherichia Coli ◽  
Saccharomyces Cerevisiae ◽  
Growth Rate ◽  
Volatile Compound ◽  
Lifespan Extension ◽  
Yeast Saccharomyces Cerevisiae ◽  
Replicative Lifespan ◽  
Solid Media ◽  
Respiratory Conditions ◽  
Ferment Glucose

Individual cells of the budding yeast Saccharomyces cerevisiae have a limited replicative potential, referred to as the replicative lifespan. We have found that both the growth rate and average replicative lifespan of S. cerevisiae cells are greatly increased in the presence of a variety of bacteria. The growth and lifespan effects are not observable when yeast are allowed to ferment glucose but are only notable on solid media when yeast are forced to respire due to the lack of a fermentable carbon source. Growth near strains of Escherichia coli containing deletions of genes needed for the production of compounds used for quorum sensing or for the production of the siderophore enterobactin also still induced the lifespan extension in yeast. Furthermore, the bacterially induced increases in growth rate and lifespan occur even across gaps in the growth medium, indicating that the bacteria are influencing the yeast through the action of a volatile compound.

scholarly journals Ehretiquinone from Onosma bracteatum Wall Exhibits Antiaging Effect on Yeasts and Mammals through Antioxidative Stress and Autophagy Induction

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yanjun Pan ◽  
Yanan Liu ◽  
Rui Fujii ◽  
Umer Farooq ◽  
Lihong Cheng ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Lifespan Extension ◽  
Oxygen Species ◽  
Replicative Lifespan ◽  
Significant Evidence ◽  
Chronological Lifespan ◽  
Healthcare Product ◽  
Autophagy Induction ◽  
Type Molecule ◽  
Antioxidative Stress

The antiaging benzoquinone-type molecule ehretiquinone was isolated in a previous study as a leading compound from the herbal medicine Onosma bracteatum wall. This paper reports the antiaging effect and mechanism of ehretiquinone by using yeasts, mammal cells, and mice. Ehretiquinone extends not only the replicative lifespan but also the chronological lifespan of yeast and the yeast-like chronological lifespan of mammal cells. Moreover, ehretiquinone increases glutathione peroxidase, catalase, and superoxide dismutase activity and reduces reactive oxygen species and malondialdehyde (MDA) levels, contributing to the lifespan extension of the yeasts. Furthermore, ehretiquinone does not extend the replicative lifespan of Δsod1, Δsod2, Δuth1, Δskn7, Δgpx, Δcat, Δatg2, and Δatg32 mutants of yeast. Crucially, ehretiquinone induces autophagy in yeasts and mice, thereby providing significant evidence on the antiaging effects of the molecule in the mammalian level. Concomitantly, the silent information regulator 2 gene, which is known for its contributions in prolonging replicative lifespan, was confirmed to be involved in the chronological lifespan of yeasts and participates in the antiaging activity of ehretiquinone. These findings suggest that ehretiquinone shows an antiaging effect through antioxidative stress, autophagy, and histone deacetylase Sir2 regulation. Therefore, ehretiquinone is a promising molecule that could be developed as an antiaging drug or healthcare product.

scholarly journals Characterization of the impact of GMP/GDP synthesis inhibition on replicative lifespan extension in yeast

2020 ◽  
Vol 66 (4) ◽  
pp. 813-822
Author(s):  
Ping Liu ◽  
Ethan A. Sarnoski ◽  
Tolga T. Olmez ◽  
Thomas Z. Young ◽  
Murat Acar
Keyword(s):  
Lifespan Extension ◽  
Replicative Lifespan ◽  
Synthesis Inhibition ◽  
The Impact

scholarly journals Informational Theory of Aging: The Life Extension Method Based on the Bone Marrow Transplantation

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Alexey V. Karnaukhov ◽  
Elena V. Karnaukhova ◽  
Larisa A. Sergievich ◽  
Natalia A. Karnaukhova ◽  
Elena V. Bogdanenko ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Genetic Similarity ◽  
Autologous Transplantation ◽  
Life Extension ◽  
Laboratory Animals ◽  
Lifespan Extension ◽  
Theory Of Aging

The method of lifespan extension that is a practical application of the informational theory of aging is proposed. In this theory, the degradation (error accumulation) of the genetic information in cells is considered a main cause of aging. According to it, our method is based on the transplantation of genetically identical (or similar) stem cells with the lower number of genomic errors to the old recipients. For humans and large mammals, this method can be realized by cryopreservation of their own stem cells, taken in a young age, for the later autologous transplantation in old age. To test this method experimentally, we chose laboratory animals of relatively short lifespan (mouse). Because it is difficult to isolate the required amount of the stem cells (e.g., bone marrow) without significant damage for animals, we used the bone marrow transplantation from sacrificed inbred young donors. It is shown that the lifespan extension of recipients depends on level of their genetic similarity (syngeneity) with donors. We have achieved the lifespan increase of the experimental mice by 34% when the transplantation of the bone marrow with high level of genetic similarity was used.

scholarly journals Sir2 phosphorylation through cAMP-PKA and CK2 signaling inhibits the lifespan extension activity of Sir2 in yeast

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Woo Kyu Kang ◽  
Yeong Hyeock Kim ◽  
Hyun Ah Kang ◽  
Ki-Sun Kwon ◽  
Jeong-Yoon Kim
Keyword(s):  
Lifespan Extension ◽  
Histone H4 ◽  
Ribosomal Protein Genes ◽  
Wild Type ◽  
Promoter Regions ◽  
Replicative Lifespan ◽  
Extension Activity ◽  
Dependent Protein ◽  
Protein Deacetylase ◽  
Wild Type Yeast

Silent information regulator 2 (Sir2), an NAD+-dependent protein deacetylase, has been proposed to be a longevity factor that plays important roles in dietary restriction (DR)-mediated lifespan extension. In this study, we show that the Sir2's role for DR-mediated lifespan extension depends on cAMP-PKA and casein kinase 2 (CK2) signaling in yeast. Sir2 partially represses the transcription of lifespan-associated genes, such as PMA1 (encoding an H+-ATPase) and many ribosomal protein genes, through deacetylation of Lys 16 of histone H4 in the promoter regions of these genes. This repression is relieved by Sir2 S473 phosphorylation, which is mediated by active cAMP-PKA and CK2 signaling. Moderate DR increases the replicative lifespan of wild-type yeast but has no effect on that of yeast expressing the Sir2-S473E or S473A allele, suggesting that the effect of Sir2 on DR-mediated lifespan extension is negatively regulated by S473 phosphorylation. Our results demonstrate a mechanism by which Sir2 contributes to lifespan extension.

scholarly journals Identification of the Target of the Retrograde Response that Mediates Replicative Lifespan Extension in Saccharomyces cerevisiae

Genetics ◽  
2016 ◽  
Vol 204 (2) ◽  
pp. 659-673 ◽  
Author(s):  
J. C. Jiang ◽  
S. W. Stumpferl ◽  
A. Tiwari ◽  
Q. Qin ◽  
J. F. Rodriguez-Quinones ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Lifespan Extension ◽  
Replicative Lifespan ◽  
Retrograde Response

scholarly journals Proteomic analysis of dietary restriction in yeast reveals a role for Hsp26 in lifespan extension

2021 ◽  
Author(s):  
Richard Campion ◽  
Leanne Bloxam ◽  
Kimberley Burrow ◽  
Philip Brownridge ◽  
Daniel Pentland ◽  
...  
Keyword(s):  
Dietary Restriction ◽  
Small Heat Shock Protein ◽  
Direct Analysis ◽  
Inhibitory Effect ◽  
Effector Proteins ◽  
Lifespan Extension ◽  
Replicative Lifespan ◽  
Downstream Effector ◽  
Proteomic Approach ◽  
Underlying Mechanisms

Dietary restriction (DR) has been shown to increase lifespan in organisms ranging from yeast to mammals. This suggests that the underlying mechanisms may be evolutionarily conserved. Indeed, upstream signalling pathways, such as TOR, are strongly linked to DR-induced longevity in various organisms. However, the downstream effector proteins that ultimately mediate lifespan extension are less clear. To shed light on this, we used a proteomic approach on budding yeast. Our reasoning was that analysis of proteome-wide changes in response to DR might enable the identification of proteins that mediate its physiological effects, including replicative lifespan extension. Of over 2500 proteins we identified by liquid chromatography-mass spectrometry, 183 were significantly altered in expression by at least 3-fold in response to DR. Most of these proteins were mitochondrial and/or had clear links to respiration and metabolism. Indeed, direct analysis of oxygen consumption confirmed that mitochondrial respiration was increased several-fold in response to DR. In addition, several key proteins involved in mating, including Ste2 and Ste6, were downregulated by DR. Consistent with this, shmoo formation in response to α-factor pheromone was reduced by DR, thus confirming the inhibitory effect of DR on yeast mating. Finally, we found that Hsp26, a member of the conserved small heat shock protein (sHSP) family, was upregulated by DR and that overexpression of Hsp26 extended yeast replicative lifespan. As overexpression of sHSPs in Caenorhabditis elegans and Drosophila has previously been shown to extend lifespan, our data on yeast Hsp26 suggest that sHSPs may be universally conserved effectors of longevity.

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