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What happens if you transfuse blood from old mice to young ones?

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Scientists have transfused blood from old mice into young ones to better understand how to lessen the effects of aging. Image credit: Buena Vista Images/Getty Images.
  • One of the hallmarks of aging is senescence, a state in which cells stop growing and dividing.
  • A new study shows that receiving a single blood transfusion from old mice caused tissue aging in young mice.
  • Treatment of aged mice with senolytic agents, which are drugs that eliminate senescent cells, before blood transfusions to young mice reduced levels of markers of senescence in young mice.
  • The study shows that senescence can occur not only from wear and tear associated with aging, but also from blood-borne factors.

A recent article published in Natural metabolism shows that a single blood transfusion from old mice to young animals can induce senescence — cellular aging — in young mice.

Identifying factors in the blood of aged animals that induce aging could help develop therapeutics that slow aging

Study author Dr. Irina Conboy, a professor at the University of California, Berkeley, said Medical News Today:

“[Our study shows that] cellular senescence is neither intrinsic to the cell nor purely chronological — a phenomenon of accumulation of damage; it can be rapidly induced within 2 weeks in young animals. Senolytics only partially reduce the negative effects of old blood on young cells and tissues, suggesting additional therapeutic avenues.

Dr. Conboy added that this study further confirms the role of old blood factors in promoting aging.

Cells tend to respond to injury or stress by undergoing cell death or entering a state where they stop multiplying. This state in which cells stop growing and dividing is known as cellular senescence.

In addition to external stimuli such as stress, intrinsic factors such as changes in DNA structure with aging can also cause senescence.

During senescence, cells can send signals to the immune system, facilitating their deletion by immune cells.

A gradual decline in the ability of the immune system to eliminate these senescent cells occurs with aging, resulting in the accumulation of senescent cells. Accumulation of senescent cells contributes to organ aging and is associated with chronic disease.

Senescent cells can also secrete molecules that signal nearby cells to also undergo senescence. These molecules secreted by senescent cells, known as the senescence-associated secretory phenotype (SASP), include pro-inflammatory proteins and other factors that remodel the neighboring tissue.

However, the influence of these factors secreted by senescent cells in promoting aging is not well understood.

Evidence from previous studies suggests that molecules or cells present in older animals can induce tissue aging in younger animals.

For example, studies have shown that surgically joining a young mouse to an older mouse can rejuvenate the tissues of the older mouse. At the same time, this procedure causes tissue aging in the younger animal.

In addition to having a common circulatory system, surgically joined animals also share organs and are exposed to a similar environment. It is therefore difficult to distinguish the potential source of pro-aging or rejuvenation factors.

Similarly, blood transfusion from older mice to younger mice can cause the tissues of the younger animal to age. These studies suggest that certain factors present in the blood of older mice can induce aging in their younger counterparts. However, it is unclear whether these pro-aging effects of old blood are due to senescent cells.

In the current study, the researchers investigated whether senescence could be transferred from older mice to younger ones through blood transfusions.

To assess the ability of old blood to induce senescence, the authors transfused blood from older mice (22-24 months) to their younger counterparts (3 months). The control group consisted of young rats (3 months) receiving blood transfusions from other young rats of the same age.

14 days after receiving the blood transfusion, young mice receiving blood from older mice showed increased expression of biomarkers of senescence in muscle, kidney and liver. However, such increased levels of markers of senescence were absent in the lungs, heart, and brain.

Young mice that received blood transfusions from older mice also showed deficits in muscle strength assessment tasks and exhibited lower physical endurance.

Similar to skeletal muscle tissue, young mice receiving blood from older mice also showed elevated levels of biomarkers for tissue damage and impaired or suboptimal function in the liver and kidneys.

The researchers also transfused blood from younger mice into older mice and found that receiving young blood reduced tissue damage in the liver, kidneys, and muscles of older mice.

In sum, these results suggest the induction of senescence in young mice after receiving blood transfusions from older mice. Moreover, the senescence induced in young animals after receiving blood from old mice was tissue-specific.

The researchers next investigated whether eliminating senescent cells in aged mice could prevent the induction of senescence in young mice after blood exchange.

For this experiment, the researchers kept the aged mice on a diet of senolytic drugs which eliminate senescent cells for about 4 to 6 weeks. As expected, treatment with the senolytic drugs reduced the levels of secreted factors associated with senescence in the plasma of aged mice.

The researchers then transfused blood from older mice treated with senolytic drugs or vehicle into young mice.

Young mice receiving blood from older senolytic-treated mice showed reduced expression of senescence markers in muscle, liver, and kidney than young mice receiving old vehicle-treated blood.

Senolytic treatment also attenuated declines in liver, muscle, and kidney function and reduced damage to these organs in young mice given old blood.

Additionally, administration of senolytics to older mice also reduced the adverse effects of old blood on physical activity levels and energy balance in younger mice.

Young mice given blood from older mice treated with senolytic drugs also showed lower levels of proteins associated with inflammation, a hallmark of senescence.

However, young mice receiving blood from older mice treated with senolysis showed some negative effects associated with old blood transfusion. For example, administering senolytics to old mice before blood transfer failed to prevent some of the negative effects on kidney function in young mice.

These experiments show that clearance of senescent cells in aged mice attenuates the pro-aging effects of transfer of old blood to young mice. In other words, in addition to being caused by stress or aging, senescence can also occur due to exposure to factors present in old blood.

Further research is needed to identify factors – such as molecules, organelles or senescent cells themselves – present in the blood that were responsible for inducing senescence in young mice.

Senescent cells secrete a number of signaling molecules into the circulation and these molecules could, at least in part, be responsible for inducing senescence. Identifying these factors could help develop therapies to delay the aging process.

Dr. James Kirkland of the Mayo Clinic Kogod Center on Aging told us:

“[This is an] interesting study that supports the effectiveness of senolytics in alleviating age-related dysfunctions. It confirms and extends previous findings that transplantation of senescent cells from old animals into young animals causes dysfunction and that removal of these senescent cells from transplanted mice restores function as well as the finding that transplantation of hearts hearts into young mice causes the spread of senescence and dysfunction in young mice while transplanting hearts from young into young mice does not.

The results of this study raise several interesting questions about aging and potential treatments to slow the aging process.

Dr. Stefan Tulius, director of the Transplant Surgery Research Laboratory at Brigham and Women’s Hospital noted that “[a]Like any great scientific contribution, this study raises many open questions in addition to providing us with a most relevant aspect of a better understanding of aging and the potential for extending a healthy lifespan.

“These open questions concern in particular the clinical relevance of the mainly experimental results: how much blood will have to be transferred to observe the effects? Will a single human blood transfusion make a difference, or will the exchange of blood have to go far beyond that? How long will the effects last? Will they be reversible and ‘only’ temporary?

“The authors report changes that included lasting target organ damage with scarring in the liver and kidneys,” Dr. Tulius added.

“Understanding the mechanisms involved in this process can be very interesting and revealing. Also interestingly, functional effects, including compromised physical activities, were observed in mice. Will they be permanent or just temporary? Moreover, if physical abilities are compromised, can we then also expect cognitive compromises? Indeed, the authors present fascinating findings raising many intriguing open questions that can guide us to better understand aging and develop new approaches to facilitate healthy aging,” he continued.