Chronic Kidney Disease Accelerates Many Aspects of Aging, Such as Cardiovascular Disease Risk

Chronic kidney disease is an unpleasant condition. There is little that can be done for patients at the present time, though there is hope that senolytic drugs might be able to turn back the fibrosis characteristic of the condition. The kidneys are important to the correct function of tissues throughout the body, and consequently chronic kidney disease accelerates the degenerative aging of many other organs, including the cardiovascular system and brain. Finding ways to restore kidney function in older patients would be a big deal.

Chronic kidney disease (CKD) is a systemic pathology that affects approximately 10% of the population. The prevalence of CKD has increased markedly over the past decades due to aging of the population worldwide and increase in incidence of diabetes mellitus, which has become the primary cause of CKD. Nowadays, CKD is considered a public health problem that causes high rates of mortality in the population due to the association with cardiovascular diseases (CVDs). Multiple studies support the notion that patients with renal disease suffer accelerated aging, which precipitates the appearance of pathologies, including CVDs, usually associated with advanced age.

Considerable efforts have been made to slow the progression of the disease and improve the quality of life in patients with CKD. New pharmacological strategies do slow the progression of CVDs, and reduce the morbidity and mortality of CKD patients. Likewise, methods of renal replacement therapy currently offer increased purification capacity and reduced adverse effects. However, the development of CVDs in patients with CKD has not yet been halted. This may be because when CKD is diagnosed, vascular pathology is already advanced and irreversible.

The causes of vascular damage in CKD are exceptionally complex. Among the theories proposed in recent years to explain the high frequency of CVDs in renal patients, one states that senescence of peripheral blood cells (known as immunosenescence) and vascular cells (known as vascular senescence) may be involved in the initiation and perpetuation of vascular pathology that appears early in patients with CKD.

The aging process that occurs due to uremia is associated with numerous changes at the cellular and molecular level, which coincide with changes observed during the physiological aging process. These changes may explain some of the complications that typically occur in patients with CKD and CKD-associated CVDs. Expanding our understanding of the factors and molecules involved in accelerated senescence will serve to identify possible targets associated with this process. This will lead to improved methods of diagnosis and monitoring of these patients. Understanding the similarities between accelerated senescence and normal physiological aging will help establish new treatments.

Link: https://doi.org/10.3389/fcell.2020.00185

Comments

My mom was on dialysis when she was about 78 years old. She was diabetic for some years and overweight(though not extremely), I often encouraged her to walk often, I imagine it annoyed her even though I suggested it "gently ".

She died at 81 cause she skipped out on the treatment once (or more) too often, or more likely, just wanted to die:(

I hope senlytics will truly alleviate many symptoms of aging, cause at 60, I don't want to see myself or others suffering a slow death.

Anyway, I also wanted to show my appreciation to not only Reason's blog ( it gives me hope), but equally to others inputs and thoughts on his daily topic. To a healthy (hopefully near) future.

Posted by: Robert at April 21st, 2020 12:55 PM

Reason,

in post from 2016 (https://www.fightaging.org/archives/2016/07/effective-therapies-to-extend-healthy-life-may-well-be-widely-available-for-a-decade-or-more-in-advance-of-definitive-proof/) you said that 5 years from then (2021) it will be possible to go overseas for senolytics treatment. You even said "I say five years and mean it". Do you still think that or we have backslided somewhat?

Also, regarding brain rejuvenation, Aubrey and Vadim had a debate (https://www.youtube.com/watch?v=gV-6g5p8jAM) and in the last 3 minutes Vadim asks him what about long lived neurons which don't get replaced to which Aubrey said that all neurons do get replaced. It seems to me that this blog (https://www.fightaging.org/archives/2018/09/tau-aggregation-in-the-aging-brain-disrupts-nuclear-pores-possibly-explaining-loss-of-function-in-alzheimers-disease/) and some papers also think that some neurons never get replaced. So why is Aubrey so confident that they do, and in much lesser periods than one human lifetime?

Finally, this blog has never mentioned SENS funded work to rejuvenate the cortex (https://www.sens.org/functional-neuron-replacement-to-rejuvenate-the-neocortex/). That guy has been on SENS conferences since the beginning of last decade. Looks like they probably could replace neurons without nanotech working on nuclear pores etc. So can you say who is right and who is wrong?

So if nuclear mutations are not a concern (as stated few days ago) and neurons can replace themselves or by us that indicates the two biggest potential SENS showstoppers are much less likely and that is great news.

Would you comment a bit on these things?

Posted by: Red at April 21st, 2020 1:02 PM

@Red:

I was wrong about going overseas - the senolytic treatment of dasatinib + quercetin is available in the US via a few physicians will to prescribe off-label, and so I haven't been paying all that much attention as to what the medical tourism market is doing with this topic.

On neuron replacement, which neurons are the topic of discussion is important. There are varying levels of evidence for different parts of the brain, and a recent controversy on the topic. It is reasonable to think that there are neurons that are never replaced, while many or most can be. What the effects on the mind are for more aggressive replacement remain to be seen. It is an area of great uncertainty.

Posted by: Reason at April 21st, 2020 2:46 PM
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