Rejuvenating Aging Organs and Blood for Transplantation

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• Transplantation as an Aging Model
• Challenges with Older Donors
• In Vitro Rejuvenation Potential
• Young Blood Protective Factors
• Old Blood Inflammatory Factors
• Future Therapeutic Opportunities
• Full Transcript

Transplantation as an Aging Model

Dr. Brian Kennedy, MD, discusses using transplantation and blood transfusion as powerful models to study the biology of aging. He explains that implanting hematopoietic stem cells to rejuvenate the blood system is a long-established practice. This provides a robust framework for understanding how aging affects tissues at a systemic level. Dr. Anton Titov, MD, explores this concept with Dr. Kennedy to understand its broader implications for medical science.

Challenges with Older Donors

A significant challenge in transplantation medicine is the limited use of tissues from older individuals. Dr. Brian Kennedy, MD, notes that beyond a certain age, people cannot be donors for transplantation, whether for organs or blood. This creates a critical shortage of available materials for life-saving procedures. Furthermore, transplanting older tissues into a younger recipient may not be beneficial. The older tissue carries systemic signaling adapted over time that could adversely affect the younger host.

In Vitro Rejuvenation Potential

A promising solution to the donor shortage is the concept of in vitro rejuvenation. Dr. Brian Kennedy, MD, describes the potential to take a tissue, blood, or an organ out and make it younger in a laboratory setting before transplantation. This approach could involve various rejuvenation strategies to reverse age-related damage. Successfully achieving this would represent a major medical breakthrough. Dr. Brian Kennedy, MD, emphasizes that this achievement could save countless lives by expanding the pool of viable donor materials.

Young Blood Protective Factors

The conversation with Dr. Anton Titov, MD, shifts to the specific science behind young blood transfusions. Dr. Brian Kennedy, MD, states there is very good evidence that young blood contains specific protective factors. These factors help to protect and maintain adult stem cells in various tissues of a recipient. This protective mechanism is a key area of interest for combating the effects of aging. However, Dr. Kennedy speculates that periodic transfusions are unlikely to be effective. He believes consistent, daily delivery would be needed to see a significant impact, making the identification of the exact factors paramount.

Old Blood Inflammatory Factors

In contrast to young blood, old blood contains factors that promote inflammation and can have adverse effects. Dr. Brian Kennedy, MD, explains that these inflammatory factors are detrimental, especially if introduced into a younger recipient. This highlights a double-edged sword in transfusion and transplantation based on donor age. The presence of these damaging compounds in aged tissues contributes to their decreased viability for donation. Understanding these negative factors is just as important as identifying the positive, protective ones.

Future Therapeutic Opportunities

The ultimate goal is to move beyond crude transfusions to targeted factor delivery. Dr. Brian Kennedy, MD, sees huge opportunity in identifying the specific protective factors found in young blood. Delivering these factors directly to patients could preserve stem cells across a wide range of tissues. This targeted approach is likely to have a substantial impact on slowing the aging process. Dr. Kennedy concludes by noting that companies focused on teasing out these specific factors are particularly exciting to watch for future therapeutic development.

Full Transcript

Dr. Anton Titov, MD: You also did fascinating research. You studied transplantation and blood transfusions as models to assess rejuvenation and aging. So how does it work?

Dr. Brian Kennedy, MD: We talk about stem cell therapy and gene therapy. People have been doing blood transfusions for a long time.

It's really about implanting hematopoietic stem cells and rejuvenating the hematopoietic system. That's been going on for a long time, so it's a good model to really study aging.

We got the idea. We wrote a review on this and worked with Dr. James Kirkland at Mayo Clinic and Stephane Julian in our group to put together some concepts about what this means.

The challenge is it is very hard to do transplants from older individuals. Once you get beyond a certain age, you can't be a donor for transplantation.

This could be organ transplantation, not just blood transfusions. We want to understand what is changing about aging.

Some questions you might consider: when you put a tissue from an older person into a younger person, that may not necessarily be a good thing. It could have systemic effects on the younger person that the older tissue has been used to signaling that's adapted over time.

We're thinking about age differences with transplantation and trying to figure out ways to rejuvenate older transplant tissues so that it can be used. There is always a shortage of these materials for transplant.

We can figure out ways to make even in vitro, take a tissue out, take blood out, take an organ out, make it younger in vitro, and then put it in a person. That could be a real achievement. It would save a lot of lives.

I think it's a good area to look at because it could have a really big impact. It allows us to study host-recipient responses, and that'll be relevant as we think about stem cell transplantation and some of the other things that are coming down the road as well.

Dr. Anton Titov, MD: What about blood transfusions? Is there actual data in humans, or maybe in experimental tissues, in vitro data, that transfusing younger blood somehow rejuvenates the tissues of the older recipient?

Dr. Brian Kennedy, MD: I think there's very good evidence that there are factors in young blood that help protect adult stem cells in various tissues in the recipient. There are also factors in old blood that are driving and promoting inflammation, so they can have an adverse effect on a young recipient.

I don't think that periodic blood transfusions are going to have much of an effect. Unless you're doing this every day, I don't think you're likely to get enough of the factors to have a huge effect. That's just my speculation.

But if we can identify what those factors are and deliver them directly, especially those protective factors, then that's a huge opportunity. Those are things that circulate and get to a whole range of different tissues.

If they can preserve your stem cells in those various tissues, it's likely to have a big impact on aging. I really think the companies that are trying to tease out those specific factors are really exciting to watch.