An Age-Related Increase in CD47 Expression Impairs Vascular Function

Researchers here provide evidence to indicate that increased expression of CD47 in aged blood vessels impairs a range of functions, from maintenance of these tissues to the generation of new blood vessels. The latter point is interesting given that capillary networks become less dense with age. This is thought to impair blood flow to tissues and thus contribute to age-related loss of function. The animal evidence here suggests that inhibition of CD47 may be a viable strategy to reduce the impact of aging on the vasculature, and thus also many of the consequences of vascular aging throughout the body.

The aged population is currently at its highest level in human history and is expected to increase further in the coming years. In humans, aging is accompanied by impaired angiogenesis, diminished blood flow, and altered metabolism, among others. A cellular mechanism that impinges upon these manifestations of aging can be a suitable target for therapeutic intervention. Here we identify cell surface receptor CD47 as a novel age-sensitive driver of vascular and metabolic dysfunction. With the natural aging process, CD47 and its ligand thrombospondin-1 were increased, concurrent with a reduction of self-renewal transcription factors OCT4, SOX2, KLF4, and cMYC in arteries from aged wild-type mice and older human subjects compared to younger controls.

These perturbations were prevented in arteries from aged CD47 knockout mice. Arterial endothelial cells isolated from aged wild-type mice displayed cellular exhaustion with decreased proliferation, migration, and tube formation compared to cells from aged CD47 knockout mice. CD47 suppressed ex vivo sprouting, in vivo angiogenesis and skeletal muscle blood flow in aged wild-type mice. Treatment of arteries from older humans with a CD47 blocking antibody mitigated the age-related deterioration in angiogenesis. Finally, aged CD47 knockout mice were resistant to age- and diet-associated weight gain, glucose intolerance, and insulin desensitizationipedia.org/wiki/Insulin_resistance">insulin desensitization.

These results indicate that the CD47-mediated signaling maladapts during aging to broadly impair endothelial self-renewal, angiogenesis, perfusion, and glucose homeostasis. Our findings provide a strong rationale for therapeutically targeting CD47 to minimize these dysfunctions during aging.

Link: https://doi.org/10.3390/cells9071695

Comments

Good. I think the negative effects of reduced circulation have been greatly underestimated. Certainly us elderly folks often feel those effects directly, especially at night, and many of the things that I do are done to address such poor circulation. Interestingly, exercise is known to increase such circulation, but its effects are limited, and circulation continues to fall with age, regardless of the finite improvement from increased exercise. So we need more innovative approaches, such as targeting CD47, to slow/stop this important part of the aging process.

Posted by: dtkamp at July 30th, 2020 10:31 AM

hopefully CD47 targets will lead soon to treatments helpful on the scale of blood pressure medications.

Posted by: cuberat at July 30th, 2020 11:15 AM

One of The Longevity Fund companies ALX Oncology works on targeting CD47 for immuno-oncology treatments. Perhaps this target will have anti-aging benefits as well?

https://alxoncology.com/science/

Posted by: Nathan Cheng at July 30th, 2020 3:19 PM

Interesting findings. A single protein with so many consequences for aging. Could be utilized as an anti-aging therapy perhaps!

Posted by: jeba sherpa at July 30th, 2020 11:10 PM

For the record, here's a review from 2017 showing that the drop in capillary density with age is likely mostly due to a corresponding drop in systemic pro-angiogenic factors, similar to the fall of sex and other hormones with age:
" Pro-Angiogenesis Therapy and Aging"
https://www.karger.com/Article/Pdf/477402

Posted by: dtkamp at August 1st, 2020 1:24 PM

Check out Dr Amen...ginko biloba and brain health? Other herbals etc. to increase blood circulation? Fish oil? Nitric oxide?

Possible inverse relationship between blood circulation and cancer incidence?

Aging is a balancing act between too much of a good thing and not enough?

Posted by: harold at August 5th, 2020 6:41 AM

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