Where's that bloody Fountain of Youth?

Mortality is perhaps one of the most humbling truths of life.

 Advances in medicine and health advocacy are allowing for average life expectancy to increase. A 2008 Nature commentary by Thomas B.L. Kirkwood presented the rate of this increase, 5 more hours onto our lives per day, in a simple and eloquent way:

Think of it this way. You woke up this morning to what is effectively a 29-hour day. Twenty-four of those hours you will use now; the other five will be put by for later. The challenge posed by population ageing translates into ensuring that these extra hours will be as good as possible…
The Fountain of Youth, 1546 painting by Lucas Cranach the Elder.

The Fountain of Youth, 1546 painting by Lucas Cranach the Elder.

 

For humans, growing old and the diverse effects of ageing we each may experience are diverse and often dreaded. Writers, philosophers and adventurers as early as Alexander the Great (who died somewhere around 323 B.C.) have swooned over a way to reverse the wear and tear on the body, hoping to stay young in body and mind forever.

 

 

Is there a Fountain of Youth?

 A trip to St. Augustine, Florida may (arguably) provide us with some “history”. While many have referred to, or been on the hunt for, the fountain of youth, Ponce de Leon is the most associated man. His gullibility in question, this 16th Century explorer from Spain struck land in present-day Florida way back in 1513, rumored to have claimed the discovery of magical waters. If you’re interested, you can jump in the nearest plane, train, or automobile and check it out yourself! St. Augustine hosts an Archaeological Park complete with fountain of youth flowing endlessly with fresh, sulfur-scented spring water. What a treat!

 I will not speculate on the anthropological accuracy of St. Augustine's fountain, but here are some truths about getting old.

 The muscles will weaken, the 20/20 vision may fade, and we may anguish each gray hair that appears. Most difficult to contend with however, may be the loss of cognitive function; meaning things like memory, perception, brain processing speed, and inductive reasoning. As someone who regularly “loses” her slippers somewhere in the apartment and walks out the door without my CTA pass, I’m slightly horrified by what old age will do to me. Can you relate? (Please say yes…)

Still frame from Pixar short film Geri's Game (1997).

Still frame from Pixar short film Geri's Game (1997).

 Brains of older adults have a tendency to show a decreased amount of grey matter compared to younger people. Grey matter is the home to tons of neuron (nerve) cells and is (generally speaking) the part of the brain that translates nerve signals into information. Less grey matter, especially in regions like the prefrontal cortex, means that basic motor, emotional and cognitive skills are at risk for impairment. This physical change in the brain doesn’t appear to be a result of neuron cells dying, rather that the density of synapses (the connections between neurons and other target cells) is less in older people. It’s easy to see that this would affect the efficiency and potentially effectiveness of information being processed. It’s even been suggested that ageing in the absence of any simultaneous diagnosis would result in brain impairment matched to that of an Alzheimer’s patient around an age of 120-130 years. Thus, despite these negative effects, it’s important to note that ageing itself is not a disease. It’s a normal physiological process that may be accompanied by, or lend itself to, an increased susceptibility to immune and neurological diseases.

Schematic diagram of a young brain versus an old brain with decreased amount of grey matter. Image from: brainpowerrelease.com.

Schematic diagram of a young brain versus an old brain with decreased amount of grey matter. Image from: brainpowerrelease.com.

 

So now that I’ve brought the mood down to a semi-depressing level and dangled the idea of immortality in front of you, let’s get to the question of the day:

 Is there really a way to reverse these effects?

 Mythical water aside, there is another liquid that has very recently been identified as having the power to reverse the normal decline in cognitive function as we age. Blood! Stay with me because this is some real science non-fiction.

 Research in the mid-to-late 2000s adapted the use of a century-old biological technique that’s going to seem straight out of Frankenstein. It’s called parabiosis. To put it simply, it’s a surgical method of connecting the circulatory system of one animal seamlessly with the circulation of another, such that blood flow is continuous and shared between the two individuals. Why in the world would someone want to do this? Scientists were asking the question of whether there was some valuable component in “young” blood that would help restore the tissues of older animals. Are you on the edge of your seat?

Reduced heart mass and decreased ventricle thickness with exposure to young circulation. Figure from Leinwand, L. A., & Harrison, B. C. (2013). Young at Heart. Cell, 153(4), 743-745.

Reduced heart mass and decreased ventricle thickness with exposure to young circulation. Figure from Leinwand, L. A., & Harrison, B. C. (2013). Young at Heart. Cell153(4), 743-745.

 By linking blood flow between a young mouse and one much older, called heterochronic (different age) parabiosis, scientists saw dramatic physical improvements in the aged individuals! Two-year-old mice that showed symptoms of stiff, thickened hearts resulting in diastolic heart failure became softer and resumed the ability to pump normally when exposed to circulation of a 2-month-old's blood. Another mouse study saw rejuvenation of skeletal muscle satellite cells, a specific type of stem cell that can become brand new muscle, along with increased strength and endurance.

You are probably saying to yourself, “But Mattina, what about the brain?!” Well that old lobe-covered mass also showed improvements when exposed to young circulation! Neurons in aged individuals have a lower density of dendrites, or branches, which would lessen the propagation of signals in the brain and affect processing of information. Additionally synaptic plasticity tends to be reduced during ageing. This refers to the general ability of a synapse to strengthen or weaken depending on use and is an important part of learning and memory skills. In mouse heterochronic parabiotic pairs, brains of older mice showed a significant increase in dendrite density as well as an increase in the expression of genes associated with synaptic plasticity; successfully rejuvenating brain structure and cell biology! While physical changes are all good and fine, the real clincher of course would be an improvement in brain function. Well let’s seal the deal then, shall we? Aged mice receiving injections of young blood plasma showed increased rate of learning with maze challenges, making less mistakes, and also had improved memory skills! Some component in the blood of young individuals was actually able to reverse cognitive impairments on brain function!

Still frame from Pixar short film Geri's Game (1997).

Still frame from Pixar short film Geri's Game (1997).

Cuddly sphinx cats. Image from: Pinterest via

Cuddly sphinx cats. Image from: Pinterest via

Totally the cat’s pajamas, am I right?!

 Don’t expect doctors to start transfusing blood from young people into our grandparents...

 It’s easy to imagine the complications involved in this both medically and ethically. While results like this are really spectacular and have produced some exciting implications, it’s important to consider the limitations of applying scientific research to our own lives at present. In the meantime, there are some simple habits we can adopt to take care of that relatively important mass we carry around in our skull. Brains aside, I would argue that all of these things are not only beneficial for your health in general, but also good for the soul. Take care of yourself, people.

  •  Move your body. Increased blood flow to the brain during and after exercise may help keep your synapses active and signal transduction in the brain strong. If you even find a way to do something you enjoy, having fun will give you a powerful dose of endorphins (i.e. you’ll feel really good too).
  •  Relax. Stress affects brain function in the hippocampus and prefrontal cortex, often through an increase in glucocorticoid levels. Ever feel like the more you have going on, the more you start forgetting things? Bingo. The Seattle Seahawks know what’s up.
  •  Sleep well. Poor quality or fragmented sleep patterns may prevent the brain’s ability to reach important phases of organizing and creating memories. Keep in mind that while our eyes are resting, the brain is still working to process information and organize the new with the existing.
  •  Do the things you do best… It seems that expertise in a given area or at a particular skill is strong knowledge that is usually unaffected by the normal process of ageing. Spend time improving and practicing the things you enjoy doing so you can be more likely to carry that with you into old age.
  •  …but also don’t be afraid to challenge yourself. It’s easy to fall into the comfort of familiarity, but by testing your mind intellectually you can enhance neurogenesis (growth of new neurons!), increase grey matter, dendritic branching and development of new synapses! Audentes fortuna iuvat. Fortune favors the bold.
  •  Go out and meet people. Just as with the experience of learning new things, social interactions are powerful enough to promote the same positive benefits. Need help? “How much does a polar bear weigh?... Enough to break the ice.”
Paris Hotel and Casino, Las Vegas. Photo credit: Jacob Andrzejczak. 

Paris Hotel and Casino, Las Vegas. Photo credit: Jacob Andrzejczak. 

 A sip from the springs of St. Augustine may be refreshing, but that fountain of youth should more accurately be flowing with something a little… messier. I absolutely wouldn’t recommend drinking it, but the ability of circulating “young” blood to improve brain function in old age makes the luring power of a fountain of youth far more understandable.

 

 It may seem grim at first, but as we age we are offered the experience of understanding how our powerful bodies and minds operate within a delicate balance of biological systems. The image of raised glasses filled with an age-altering elixir is not something I can envision in the future, but hey, you never know exactly where science may lead. There’s beauty in the wonder.

If the general tendency of natural selection has been towards greater robustness, then understanding ageing is the way to secure insights into the limitations and trade-offs that make robustness imperfect.
— Thomas B. L. Kirkwood, A systematic look at an old problem (Nature 2008).