Senescence is supposed to prevent cancer formation!

Senescence – is the cells inability to continue dividing once a certain cell age has been reached – is actually an inherent tumor-prevention mechanism:

the old cells – if they have already degenerated – should not be able to spread any further, which is why their cell division is switched off.


Chemotherapy and radiation induce quite a lot of senescence

Chemotherapy switches quite a lot of – healthy – cells in the body to senescence – in technical jargon this is called “therapy-induced senolytic cells” = TIS

As a result, the patient has seriously aged after chemo.

BLUE in the picture below: Mega amount of SENESCENT CELLS after chemotherapy with doxorubicin

(c) Cellular senescence promotes adverse effects of chemotherapy and cancer relapse | Marco Demaria et al Cancer Discov. 2017 February ; 7(2): 165-176


Senescent cells poison the environment

because the senescent cells release “poisonous vesicles” – so-called inflammatory exosomes – they infect the environment and many secondary – “paracrine senescent cells” develop around a senescent cell.

(c) journal mol. medical & Wendy East

Just as one bad apple can infect a whole basket.

As I have shown in several articles, the senescent cells secrete EXOSOMES – little bubbles – filled with inflammatory messengers and other nasty stuff that slowly poisons the body.

Action Mechanisms of Small Extracellular Vesicles in Inflammaging by Rocío Mato-Basalo, Life Volume 12 Issue 4 10.3390/life12040546


Text from the study with the blue mouse…

…. the elimination of TIS cells reduces many short- and long-term side effects of chemo-drugs, including bone marrow suppression, cardiac dysfunction, cancer recurrence, and physical activity and strength.

The risk of chemotherapy-induced tiredness (fatigue) was significantly increased in people with increased expression of a senescence marker in T cells. These findings indicate that it is actually the senescent cells that can cause many side effects of chemotherapy. Senolysis Offers a New Target to Reduce Toxicity of Cancer Treatments (2017 Study Abstract)


Chemo leaves behind living – senescent – ​​cancer cells

not all cancer cells are completely destroyed by chemotherapy.

Many cancer cells get stuck in the senescent state due to the chemo – although they can no longer divide, they fight against senescence and poison the body with SENSCENCE – ASSOCIATED – SECRETORIC PROTEINS (SASP)

This leads to a significantly increased tumor pressure, from which RECURSIONS or SECOND TUMORS arise (study 2017)

This is often the case in practice: tumors “encapsulate” after chemotherapy and slowly become smaller and smaller. Here, the tumor cells were not completely killed but switched to senescent, they can no longer divide (study 2019).

Many cancer cells are not killed by chemotherapy but become senescent.

But they try to fight it and if they manage to overcome senescence, patients experience tumor recurrence.

In addition, many normal, healthy cells become senescent as a result of chemotherapy or radiation, as I have shown with the “blue mouse” in the picture above. Unfortunately, these then poison the environment with their SASP exosomes and even induce new tumors.


these senescent cancer cells struggle to revive

like all senescent cells, the chemo-silenced cancer cells release exosomes filled with inflammatory signaling molecules (SASP) and thus poison the environment.

(c) Chemotherapy-induced senescence, an adaptive mechanism driving resistance and tumor heterogeneity Jordan Guillon et al. (Review) | CELL CYCLE 2019, VOL. 18, NO. 19, 2385-2397

These SASP’s help the senescent tumor cells in the sense of developing a very heterogeneous cell transformation, whereby the cancer cells e.g.  gets rid of important receptors or kinase-enzymes or hormon-sites and thus frees themselves from such a treatment and becomes resistent (Studie 2019)


senescent cancer cells eat healthy cells to resurrect

I would never have thought the following possible, I just didn’t have that much imagination:

The study from 2019 shows an unbelievable fight for survival at the cellular level: cancer cells senescent through chemotherapy eat surrounding cells in order to get back into cell division and growth via their genetic apparatus.

Chemotherapy-induced senescent cancer cells engulf other cells to enhance their survival | Crystal A. Tonnessen-Murray1 et al, J. Cell Biol. 2019 Vol. 218 No. 11 3827-3844


Senolysis also eliminates the senescent tumor cells and is therefore usually a good tumor recurrence prophylaxis -> many studies


lots of research going on

here below I have already researched for some types of tumors and shown corresponding studies through which senolysis would be suggested as an additional therapy after chemotherapy has taken place.

I shall add other types of tumors here in the next few weeks


prostate cancer

1300 entries currently on Scholar

hormone therapy causes prostate cancer cells to become senescent and stop growing. They then respond well to senolysis and can be cleared away with it.

However, different hormone therapeutics lead to different responses to the senolytics: enzalutamide produces “normal senolytic cells”, but high-dose androgen therapy produces “senolysis-resistant cells”. Study 2020

Androgen deprivation-induced senescence in prostate cancer cells is conducive to the development of hormone resistance but renders the cells treatable for a senolytic therapy study 2021

Special proteins in senescent prostate cancer cells indicate whether these cells will later develop and become resistant to both chemotherapy and hormone blockers. However, these senescent cells respond to senolytic therapy. Study 2021

  • When screening about 10 studies, I only see advantages and no disadvantages when using senolysis in (previously or currently) existing prostate cancer


pancreatic carcinoma

nice research -> makes sense

Mutated p53 activates KRAS and helps pancreatic carcinoma to senescence and aggressively metastasize – 2010 study

Pancreatitis alters senescent, borderline malignant pancreatic cells via inflammatory factors in such a way that they degenerate aggressively into cancer. Anti-inflammatories block this, should therefore be given to pancreatitis, senescent cells then develop (which can be cleared away with senolysis). Study 2011

Great Review 2021 Pancreas-Ca is initially mutated relatively little, which is why the immune system can only recognize it with difficulty. Later mutated very heterogeneously and therefore not well treatable, full of dense, inflammatory stroma – 90% of the tumor – very badly fibrosed and poorly perfused with little oxygen. Many senescent cells secrete pro-inflammatory SAPS which promote the inflammatory pro-carcinogenic tumor environment.

interesting section from this review

this paragraph is so important that I translated it 1:1. The numbers refer to the reference linked in the review.

Senescence was first described as the cessation of cell proliferation in diploid cells caused by telomere shortening [90].

Since then, different mechanisms of senescence have been described in several cell types, including fibroblasts [91], epithelial [92], endothelial [93] and mesenchymal stem cells [94] as well as in cancer cells [95].

The main triggers of senescence = cell aging can be divided into two main categories: developmental and stress-related [96].

While the former is involved in embryonic development, wound healing and tissue remodeling [97], stress-induced senescence is a pathological manifestation triggered by a pro-inflammatory microenvironment [98].

Although the link between aging and senescence is clear, these pathological events are not necessarily age-related.

In fact, senescence can occur independently of age in response to damage [99] by e.g

Damage that triggers senescence

  • such as genotoxic influences [100],
  • oncogenic [101] stress
  • oxidative stress [102],
  • epigenetic modifications,
  • chromatin remodeling [103],
  • unbalanced proteostasis [104]
  • or mitochondrial dysfunction [104].

Each of these signals induces a different type of senescence. Replicative senescence, programmed senescence and stress-induced premature senescence (SIPS) have been described above.

SIPS (= stress-induced premature senescence) starts when

  • oncogene-induced senescence (OIS),
  • senescence induced by DNA damage,
  • epigenetically induced senescence and
  • mitochondrial dysfunction associated senescence as well
  • therapy-induced senescence (TIS) [105].

Despite a lack of clear markers of senescence, it is generally accepted that senescent cells share some common features regardless of the type of induction [106].

The main characteristics that senescent cells have in common are

  • stable growth standstill – can no longer divide cells
  • Resistance to apoptosis – can no longer die
  • Chromatin remodeling – genetic material changes
  • persistent DNA damage repair attempt (DDR),
  • increased activity of senescence-associated beta-galactosidase (SA-β-Gal)
  • Secretion of several pro-inflammatory molecules, which are called “senescence-associated secretory phenotype” (SASP) as a typical hallmark of senescence [13,107].

this passage is so informative that I have translated it 1:1 as it clearly shows that any significant disturbance in the body will result in senescence which as we know is ‘contagious’ and eventually leads to cancer.

in pancreatic carcinoma, the senescent cells are “the beginning” of the cancers existence. They gradually degenerate, the whole thing is favored and accelerated by low-threshold inflammation.

Stromal cells are senescented by chemotherapy or oxidative stress (H2O2) (page 10 of the review). Irradiation in particular throws the stromal cells into senescence and they then eject very high doses of cancer-promoting factors (see IL-6, IL-8, and
osteopontin) as well as fibrosing factors (i.e., TGF-β1, TNF-α, and IL-1).

In the graphic below you can see the mutual control via the SAPS exosomes in the form of the small yellow bubbles between the individual cells.

pro-tumor-promoting effects of tumor therapy – Int. J. Mol. Sci. 2022, 23, 254 (page 11)

first of all I understand for the FIRST TIME the reason and how accumulation of IMMUNSUPPRESSIVE TREGS in cancer occurs. These “master cells of immune inhibitionare the result of the SAPS exosomes from the senescent tumor cells or other senescent cells which grow the Tregs out of the precursor T cells with TGF-ß1.

At the same time, the review points out that the active T cells themselves become secondary senescent through the SAPS exosomes and are therefore immunologically inactive and also induce Tregs!!!!

Prostaglandin-2 secretion by the tumor cells inhibits the NK killer cells -> hence the effect of fish oil in tumor therapy!#

the review closes with the following paragraph

Strategies to combat senescence in cancer have emerged in the United States.
In particular, an innovative “one-two punch” approach could pave the way for the use of senotherapeutics in cancer treatment.

This approach consists of inducing senescence in both tumor and non-tumor cells by administering anticancer drugs in clinical doses (=chemo) followed by a senotherapeutic drug that selectively eliminates senescent cells (=senolysis)

In this way, on the one hand, tumor progression, relapse and chemo
resistances are prevented, thereby preventing the deleterious accumulation of senescent cells within the tumor;


are there any tests done already for “one-two-punch”?

Nice example here in the enormously laborious 2020 study: first, a new chemo agent is used to trigger senescence in pancreatic carcinoma cells, which are then cleared away with senolysis (about 30%).


now lets look at Intestinal Cancer, ColonCa, Rectum-Ca

2018 study shows that chemo-treated colon cancer cells show typical senescence characteristics.


Baikalin inhibits colon cancer in vitro and in vivo via apoptosis and senescence

A very complex and extensive study from 2018 shows an approx. 50% inhibition of colon cancer in the mouse model with strong induction of apoptosis by administration of Baikalin. Both apoptosis induction and senescence are the mechanisms by which Baikalin acts.




… will be continued,

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