Senescent Cells Contribute to the Harms Caused by Aged Blood
The present state of parabiosis studies demonstrates that diluting blood in old animals produces improved health, whether this is achieved using saline or young blood. Thus we expect there to be few beneficial factors in young blood, and many harmful factors in old blood. So far there has been mixed or little benefit noted in studies in which young plasma is transfused into old recipients, but dilution appears more promising.
As noted here, the growing burden of senescent cells in aged tissue is a significant source of those harmful factors. Senescent cells are very active, generating a mix of factors known as the senescence-associated secretory phenotype (SASP). Much of this is inflammatory signaling, which when sustained for the long term causes a broad range of disarray in the immune system and tissue function. That includes encouraging more cells to become senescent, a feedback loop of damage and signaling, like much of aging.
Does aging damage drive the pro-aging signaling environment in old plasma? Or does old plasma cause the aging damage? Researchers chose to look at the interplay between circulating factors and senescent cells, because each of them is known to worsen the other. Could "pro-aging" factors in blood from a biologically aged organism drive aging damage in a young animal? The answer: Yes. When they bathed cells from the deep layers of mouse skin in old mouse blood, the cells began to exhibit signs of senescence.
In living, breathing mice, even a single round of old blood transfusion was enough to push a substantial number of the cells in young mice into senescence. The effect emerged within the first two days, and even more senescent cells crept into the young animals' tissues over the following two weeks. And the corrosive spread of senescent cell markers was accompanied by a surge of circulating SASP factors in the young animals' blood. Between the eruption of senescent cells in their tissues and the tainting of their blood with "pro-aging" factors, the young mice became afflicted with many of the infirmities of old age. The aged blood sapped them of strength and endurance, fat infiltrated their muscles, they suffered minor kidney damage, and their liver function declined as the organ became somewhat fibrotic.
Why does an animal's blood become fouled with these baleful proteins with age? All of this deranged "pro-aging" signaling is the agonized biochemical crying-out of a body riddled with aging damage. As cells and essential biomolecules become damaged, they increasingly function abnormally, including in the production and reception of signaling molecules.
Researchers set out to purge the tissues of aged mice of a significant number of their senescent cells using either of two different drug regimens that destroy senescent cells: Navitoclax or the cocktail dasatinib plus quercetin (D+Q). Then they would see if having removed some of that damage from the old animals' tissues would make their blood less "pro-aging." And that's exactly what happened. Pretreating an old mouse with either senolytic approach before transferring its blood into a young mouse greatly reduced the "pro-aging" effects of its blood on the young animal, driving fewer of the young mouse's cells into senescence and causing less organ dysfunction
I think a good test would be seeing how an old mouse's tissues etc acted after getting half its blood replaced by an old mouse's blood that had half its blood replaced in a NBE and then compare that to the replcement with young mouse blood.
Not sure if just having less SASP/senescent cells in replacement old blood would give as big an effect as that.
Are aged human blood donors also inadvertently donating senescent cells to blood recipients? Is it possible that say an emergency donation from an older donor saves a younger recipients life only to rapidly age the younger recipient? Better than dying on the spot, but what about non-emergency blood donations? In this case I would definitely want to know the donors age if I was getting a blood donation. Who wants pro-aging cells as well? This could be ugly. It's hard enough getting people to donate blood but what happens if people start refusing donations from aged donors because they fear the loss of lifespan years?
When I donate blood, does the replacement blood that I make for myself count as new blood, meaning similar enough to that of receiving a transfusion from a younger person?