many of the clinical trials currently underway for senolysis were all initiated around 2019 and presumably interrupted by COVID.
Since the senolysis is carried out with FDA approved and tested leukemia drugs – used repurposed – I am researching possible interactions or contraindications for patients having in pre-existing diseases, since potential senolysis usually affects old, multimorbid patients.
Very briefly recap what it is all about – what is senescence
Aging and severe stress shoot cells into “senescence”, a state where they can no longer regenerate through cell division – but at the same time can no longer die. These cells release small vesicles – EXOSOMES – filled with inflammatory factors which now – secondarily – “poison” other cells and force them into senescence. This causes a lot of “old age diseases” and also cancer.
Like ONE rotten apple spoiling a whole basket of apples!
Like a rotten apple infecting the surrounding area, senescent cells spread to the surrounding area and infect other cells, causing the affected tissue to age faster and faster!
Way out – SENOLYSIS
The senescent cells can be killed by “senolysis” – a therapy with relatively harmless drugs (leukemia drugs) – their place is taken by stem cells, which can now regenerate the tissue. For me, this senescence regenerated my heart.
ongoing or completed clinical studies on senolysis
Date August 28, 2022
- Osteoporosis (120 participants) NCT04313634
- chronic kidney disease (9 participants around 68 years old) NCT02848131 – study was preliminary published with only 9 patients -> 2019 – shows a 30-50% reduction in senescence markers in blood, skin, adipose tissue. 9 doses of DQ were administered within 3 weeks – for side effects see *
- Status after chemotherapy for childhood cancer (60 participants) NCT04733534
- Early Alzheimer’s disease (13 participants), senolysis every 2 weeks for 12 wk NCT05422885
- Modulating the course of Alzheimer’s disease (5 participants), NCT04063124
- Alzheimer’s Phase II clinical trial (48 participants), NCT04685590
- Risk for Alzheimer’s (12 participants), NCT05422885
- Osteoarthritis (60 participants), NCT05276895, good overview of further senolysis studies
- Stem cell transplant survivors (10 participants) NCT02652052
- COVID-19 Infection – Antisenescence to Reduce Inflammatory Flare (80 participants) NCT04476953
- Frailty and markers of inflammation in the elderly (40 participants) NCT03675724
- Inflammation, stem cells in diabetics with chron. Kidney disease (30 participants) NCT03325322
- Skeletal Health of Old People (120 participants) NCT04313634
- nonalcoholic liver cirrhosis and liver fibrosis (30 participants) NCT05506488
- interstitial pulmonary fibrosis (14 participants): 2018 published no success, little subjective improvement but no indication of any improvement in clinical factors -> see comment on LinkedIn by Karl Blirando:
Karl points out that such a short and low level of senolysis cannot have any effect on such an advanced proinflammatory disease. the senolysis would have to be done by antiinflamm. and stem cell stimulation to bring anything (this is corroborated by the Osman Kibar / Biosplice results I showed in the article “The Incredibly Brave New World of Stem Cells”).
** there the list of side effects that occurred during the study
we can assume that senolysis can be carried out safely in diseases for which there are ongoing clinical studies (the drugs have been tried and tested for years and have an easily assessable potential for side effects).
Side effects that occurred in the published studies
* Side effects
9 patients about 68 years old – with chronic diabetic kidney disease.
During the course of this study, no serious adverse events (i.e. hospitalization, kidney internal jury requiring dialysis, or death) occurred and no subjects required drug discontinuation.
** Side effects
14 participants 70 years old, all suffering from interstitial pulmonary fibrosis for decades
Events and symptoms were mild to moderate, reversible, and without clinically significant consequences, per MedDRA v16.1. The most common events were
- Respiratory symptoms (a total of 14 occurrences: cough, shortness of breath, runny nose),
- Skin irritation and bruising following study skin biopsies (n=14 reports; 11 related to biopsy or adhesives)
- Gastrointestinal complaints or heartburn (n = 12).
- two headache events led to transient discontinuation of planned activities and were conservatively classified as “severe”.
- A serious adverse event has occurred after completion of DQ treatment (possible bacterial multifocal pneumonia and pulmonary edema superimposed on the presence of interstitial pulmonary fibrosis), resulting in a temporary hospitalization followed by a full recovery.
Below I collect other conditions / diseases where senolysis could possibly be performed
EBV-associated tumors
B-cell lymphomas, Burkitt’s lymphomas, lymphoblastic, etc: improved by dasatinib in vivo, study 2012
BUT: Splenomegaly and infiltration by EBV lymphoma cells is worsened by dasatinib in vitro study 2020 -> the question is whether a 2-3 day application as for senolysis is also “bad”.
POST-COVID issues
Review shows clear senescence and also positive results from senolysis
Covid therapies
https://erj.ersjournals.com/content/early/2022/06/21/13993003.01101-2022.abstract
chronic kidney disease
seems to be very clearly a senescence-associated KH,
- here a Chinese study 2017
- here an Argentinian study 2016 presenting an algorithm HUGO to differentiate SENESCENCE from chronic kidney disease
- Swedish MiniReview 2019 on senolysis as a way to improve kidney disease
- UK Reveiw 2019 on kidney senescence and treatment options
….. to be continued …..
