Immortal Mice and Men

My inner biology geek was thrilled with the recent "vampire mice" studies that hit mainstream media last week. There were three studies that together formulated the content behind the attention-grabbing headlines "Young Blood Restores Old Mice" and "Could Young Blood Be the Fountain of Youth?"

All three studies focused broadly on a central scientific question: How does the presence of young blood in an aged mouse change or alter the aging process? Is the key to elusive immortality actually within our own cells at the beginning of our lives? It is a thought-provoking question to ask. I have always believed that science and philosophy are close twins, and this group of papers solidified that belief.

The Nature paper, "Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice," took a very direct route to answering the central question. It has been known for several years that exposure to young blood can improve stem cell function in various organs of older mice, including the liver, muscle, spinal cord and brain. However, while regeneration in the brain had been shown, no one had yet proved that there is actual improvement in cognitive processes. The authors carefully proved, step by step, that there was an improvement in cognitive process through showing both behavioral and biological evidence. The missing piece here is how this happens. While relevant proteins are identified as possible mechanistic targets, the authors pose the biggest question of all at the end of the paper:

One possibility is that introducing 'pro-youthful' factors from young blood can reverse age-related impairments in the brain, and a second possibility is that abrogating pro-aging factors from aged blood can counteract such impairments.

In other words, exposure to young blood may help older mice by giving them youth, or by diluting the aging factors.

The other two papers, "Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle" and "Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors," attempted to answer this question by focusing on a specific protein within young blood that was hypothesized to cause changes: GDF11 (growth differentiation factor 11). Levels of this protein are high in young mice and lower in older mice. In the papers, the role of GDF11 in aging was tested in skeletal and brain tissues. GDF11 was clearly shown to have rejuvenating effects in heterochronic parabioitic models (where blood is shared between a young mouse and older mouse), and in mice that received GDF11 alone.

To simplify: GDF11 is a single protein that can have a restorative impact on the brain and skeletal muscle. There is an obvious and impressive pharmaceutical angle here to understand. However, I was most fascinated by another aspect of the paper that raises a myriad of ethical and policy questions.

We show here that blood from 15-month-old mice does not have a detrimental effect on young mice, whereas older blood (21 months old) dramatically decreases neural stem populations in the young brain, an effect also observed in the hippocampus.

So, yes, young blood can be restorative, and that's phenomenal news, even if we don't know exactly how. However, if old blood can be degenerative, there are wide-ranging and frightening consequences to blood donation and transplants. Are we accidentally hastening the aging process in patients as we try to save them? How do we take morally responsible steps to investigate this, and then to act on our findings?

Several centuries ago, much like our authors, another brilliant scientist pontificated on immortality. Plato remarked in the Last Days of Socrates, "To be afraid of death is only another form of thinking that one is wise when one is not; it is to think that one knows what one does not know."

It is perhaps fitting that with an advancement toward the eventual pursuit of immortality, we stand at a crossroads where the understanding of what we do not fully understand we do not know is absolutely critical to moving forward. We need to gain clarity on what truly is causing the "anti-aging" effects and begin research in humans to study this further. And the sooner the better; none of us is getting any younger!