cell senescence

anonymous asked:

there is no way Kaneki to healing? He can't live like this....

I talked about it a little bit here [x] but like Furuta mentioned, Kaneki seems to have reached his limit. 

As in, he’s regenerated so much over the course of the series that his telomeres are gone. Whenever a cell divides, DNA shortens. Obviously you don’t want to lose any important DNA, so instead of shortening the genes themselves, a small portion of the telomere on the end of chromosomes is sacrificed. That’s it’s job- to be sacrificial DNA. When a telomere is all used up, to stop any damage to your genes themselves (causing disease) your cell either goes into senescence (I guess “put into a coma”) or commits cell suicide.

That’s what stage Kaneki is at now. The parts of his body that have sustained the most damage (which is now HIS ENTIRE TORSO) have used up all their telomeres. He’s not regenerating anymore. The cells in his body are dying. You’re right- he can’t live like this.

Nishiki mentioned cannibalism as a means to halt the aging

and if Kaneki can somehow manage to cannibalise the Oggai, I think he’ll have a chance. I personally believe this could be the ‘Dragon’ Furuta keeps mentioning.

but what I’m worried about is that it’s a short term solution and that he’ll never be able to reverse that aging he’s already been through, only ingest new Rc cells to form a kagune and to “fill up the holes” when he gets wounded.

HeLa cells, an immortalized cell line

Frequently, scientists try to understand how the cells in our body behave by culturing them in a dish. But normal cells eventually stop dividing and die, so studying cells that can grow “forever” has become an invaluable tool in scientific research. These are HeLa cells, the first immortalized cell line ever established by scientists. HeLa cells are cervical cancer cells that were surgically removed in the 1940s from an African-American woman, Henrietta Lacks (whose story was recently documented by Rebecca Skloot in The Immortal Life of Henrietta Lacks). Since the establishment of HeLa, thousands of immortalized cell types have been developed, but HeLa cells remain the most commonly used one.

Image by Asae Igarashi, Kyowa Hakko Kirin Co. Ltd., Japan.

Oncogenes and tumour suppressors are mutation targets promoting the onset and maintenance of cancer. Oncogenic mutations result in gain-of-function and deregulation of the function of the oncoprotein that they encode. Tumour suppressors act to run quality checking of DNA, keep cell cycle checkpoints, and shut down mitogenic signals; mutations in genes encoding tumour suppressors can lead to absence of these checks and give activated oncoproteins the chance to run riot in a cell. Co-incidence of mutations in oncogenes and tumour suppressor genes potentially leads to cancer.


Ras is a small G protein involved in a whole host of cellular functions. Mutation of Ras at a functional site can lead to a pleiotropic phenotype. Oncogenic Ras causes inappropriate signalling through its three pathways: MAPK, PI3K, and RalGEF. Signalling through the PI3K activates antiapoptotic Akt (PKB), which acts to promote cell survival. Signalling through RalGEF causes cell motility by formation of filopodia (Cdc42) and lamellipodia (Rac), which may be associated with metastasis. Signalling through MAPK actually causes the expression of some Ras signalling inhibitors (Sproutys, SPREDs, GAPs) which shuts down the signal in normal cells.

Myc is a transcription factor with more than 8000 transcription targets. Deregulated Myc leads to cell proliferation, but does not block apoptosis. Thus, it leads to a modest amount of growth before it is eradicated by apoptosis. Inhibition of apoptosis by antiapoptotic Bcl-xL is tumourigenic in cells expressing Myc highly. Additionally, Myc is thought to contribute to the tumour microenvironment, immune evasion, and inhibition of differentiation.

Ras and Myc work together by combining their abilities. Myc promotes cell proliferation and disfavours differentiation, and Ras inhibits apoptosis. The combination of the two means that cells are allowed to proliferate without triggering apoptosis. Ras actually activates Myc in normal cells - but in normal cells, activation is transient. Ras stabilises Myc by phosphorylation on S62 through MEK signalling, but also promotes its degradation by phosphorylation on T58 through PI3K signalling. The result is transient activation of Myc by Ras. Mutations which ultimately block phosphorylation at T58 will switch activation by Ras from a transient to a constitutive response.

Tumour suppressors

p53 is the so-called guardian of the genome. High Myc and oncogenic Ras cause stabilisation and activation of p53. p53 gets two bites at the cherry to combat the inheritance of damaged genomes: at the point of DNA damage, p53 arrests the cell until the DNA is repaired. p53 decides whether the cell enters senescence or apoptosis - its own state of post-translational modifications and the genomic context of its target genes (p53 is also a TF) on the genome in that particular cell both play a role in which way the scale tips. In this way, p53’s second bite of the cherry is the selection of apoptosis in cells whose DNA is damaged beyond repair.

Rb is the keeper of the G1/S checkpoint. Loss of both copies of the Rb gene leads to retinoblastoma. Familial retinoblastoma predisposes heterozygotes with a heightened risk of retinoblastoma by loss of heterozygosity - loss of their only functional copy. This can occur by mutation, but also by mitotic recombination, gene conversion, and nondisjunction. Cells null for Rb can still enter G0 phase, as p107 and p130 share some redundant functions with Rb.

NF1 displays the phenomenon of haploinsufficiency. Nf1-/- Schwann cells can be complemented for the wild-type by Nf1+/+ mast cells, but not Nf1+/- mast cells. The former gives the wild-type; the latter causes neurofibromas.

VHL suppresses the hypoxic response in normoxia by mediating the ubiquitin-associated degradation of HIF-1α in normoxia. Loss of VHL leads to a hypoxic response no matter the oxygen level.

Further reading:

  • Hanahan, D.; Weinberg, R.A. 2011. “Hallmarks of cancer: The next generation.” Cell 144:646-674.
  • Lowe, S.W.; Cepero, E.; Evan, G. 2004. “Intrinsic tumour suppression.” Nature 432:307-315.
  • Pylayeva-Gupta, Y.; Grabocka, E.; Bar-Sagi, D. 2011. “RAS oncogenes: Weaving a tumorigenic web.” Nature Reviews Cancer 11:761-774.
  • Soucek, L.; Evan, G.I. 2010. “The ups and downs of Myc biology.” Current Opinion in Genetics and Development 20:91-95.
  • Vousden, K.H.; Prives, C.; 2009. “Blinded by the light: The growing complexity of p53.” Cell 137:413-431.
  • Burkhart, D.L.; Sage, J. 2008. “Cellular mechanisms of tumour suppression by the retinoblastoma gene.” Nature Reviews Cancer 8:671-682.
A team of scientists might have just come up with a cure for ageing

A new class of drugs has been identified that slow the ageing process in mice, alleviating symptoms of frailty and extending a healthy lifespan. If their effect on humans is as marked as it is on animal models, their benefit could be enormous.

The research was carried out by a team from Mayo Clinic, The Scripps Institute and other institutions and published in the journal Aging Cell yesterday.“We view this study as a big, first step toward developing treatments that can be given safely to patients to extend healthspan or to treat age-related diseases and disorders,” said co-lead author and TSRI Professor Paul Robbins, PhD.“When senolytic agents, like the combination we identified, are used clinically, the results could be transformative.”“

The prototypes of these senolytic agents have more than proven their ability to alleviate multiple characteristics associated with ageing,” added Mayo Clinic Professor James Kirkland, MD, who also worked on the study. “It may eventually become feasible to delay, prevent, alleviate or even reverse multiple chronic diseases and disabilities as a group, instead of just one at a time."Senolytics target senescent cells, the ones which have stopped dividing and accumulate as we age, accelerating the ageing process.

(excerpt - click the link for the complete article)