LONGECITY

Angiotensin II (Ang II) induces reactive oxygen species (ROS) production by human vascular smooth muscle cells (hVSMCs). ROS have been implicated in the development of both acute stress-induced premature senescence (SIPS) and chronic replicative senescence. Global oxidative DNA damage triggers SIPS and telomere DNA damage accelerates replicative senescence, both mediated via p53. This study tests the hypothesis that DNA is an important target for Ang II-induced ROS leading to senescence via telomere-dependent and independent pathways. DNA damage was quantified using the Comet assay, telomere DNA length by Southern blotting and hVSMC senescence by senescence-associated beta-galactosidase staining. Exposure to Ang II increased DNA damage in hVSMCs within 4 hours. Inhibition by an AT1 receptor antagonist (losartan metabolite: E3174) or catalase, confirmed that Ang II-induced DNA damage was AT1 receptor-mediated, via the induction of ROS. Acute exposure to Ang II resulted in SIPS within 24 hours that was prevented by coincubation with E3174 or catalase. SIPS was associated with increased p53 expression but was not dependent on telomere attrition because overexpression of human telomerase did not prevent Ang II-induced SIPS. Exposure to Ang II over several population doublings accelerated the rate of telomere attrition (by >2-fold) and induced premature replicative senescence of hVSMCs--an effect that was also attenuated by E3174 or catalase. These data demonstrate that Ang II-induced ROS-mediated DNA damage results in accelerated biological aging of hVSMCs via 2 mechanisms: (1) Acute SIPS, which is telomere independent, and (2) accelerated replicative senescence which is associated with accelerated telomere attrition.

 

https://www.ncbi.nlm...ubmed/17991883 

 

Angiotensin II

 

Edited by Kentavr, 24 February 2018 - 07:09 AM.

Interesting.

The effects of the sartans on longevity has been known for a while, but not the exact mechanism. They have been shown to extend the LS of rats.

I commenced taking Losartan in 2015. I had already been taking aspirin and Betaxolol (a Beta-receptor blocker) since 2010 and metformin since 2012.

I recently had my age estimated by the DNA-methylation method and the result was 57. My age is actually 61, so not a huge difference, (about 6.5%) but it's in the right direction.

I cannot attribute the result to Losartan or the others as I doubt I have been taking them long enough.

I hope to soon add Rapamycin to my supplements.

FWIW.

I take:

 

Aspirin: 100 mg/day (evening).

Betaxolol (Sold as "Lokren" in Russia): 5mg/day (morning)

Metformin ("Glucophage"): 250mg AM and 250mg PM

Losartan: 25mg Mon, Wed, Fri (Evening)

 

I take lots of other herbal extracts, vitamins etc but I regard these 4 (above) as most important for me. I get them when I am in Russia (not the aspirin, but the other 3) as I don't need a doctor's script.

 

I sent my sample to "My DNAge", which is a spin-off company of Zymo (USA). They are licensed to carry out the methylation analysis developed by Steve Horvath.

 

 

Where are you from?
You speak Russian?

From Australia.

I speak Russian...very badly!

I spent a lot of time in Krasnodar. :((

My wife is from Krasnodar.

 

Good afternoon, drtom!

 

I ask you to write your full method.

I need this for analysis.

 

At the moment I am working out a method of changing the profile of DNA methylation on a younger one.

 

If it's not difficult for you, share your full method, please.

 

 

Hi Kentavr!

 

Sorry for slow reply; I only just read your post.

What do you mean by "full method"?

Do you mean full list of supplements?

 

Dr Tom

Well that stinks. I take Lisinopril and was just about to add Nebivolol.

Yes, if it's possible. Also, I ask you to give the commercial names of all types of medicines and herbs.

Also I'm planning to give you advice on how to improve your regime.

There are more interesting geroprotectors.