Old Before Her Time

Kimberly Akimbo and the Lessons of Progeria

Sometimes a disease is not just a disease.

This past April, Rachel and I went to see Kimberly Akimbo, a Broadway musical about a High School girl in New Jersey. The title character is smart, funny, and quirky – a typical, precocious American girl in every way except for a rare disease that makes her age four times faster than normal.

With a life expectancy of fifteen to twenty years, teenage Kimberly is already approaching the end of her biological lifespan, a young girl trapped in the body of an old woman – complete with wrinkles, thinning hair, arthritic hips, and a failing heart.

It’s a great show – you should totally see it – for which Victoria Clark deservedly won the Tony Award this past June for Best Actress in a Musical.

The play uses Kimberly’s illness as a potent metaphor – for the awkwardness and embarrassment of teenagehood, with its universal sense that your real, inner self is not reflected by your changing, outer body; for the emotional challenges of parenthood, and the difficulty of reconciling who your child is with how you imagined they would be; for the cruelty of other people, both intentional and unintentional; and for the magic of love and friendship.

But Kimberly’s condition is not just a metaphor, it’s also a real disease, called Progeria. In the pantheon of rare diseases, Progeria, also known as Hutchinson-Gifford syndrome, is definitely one of the craziest. You might think that a lot of major things would have to go wrong to cause such a dramatic and unusual outcome as premature aging, but you would be wrong.

Progeria, which has a frequency of 1 in 18 million, is caused by a spontaneous genetic mutation in a single base pair. Think of it like this. Each egg or sperm cell in the human body has 23 chromosomes. Those chromosomes contain over 20 thousand genes, each one carrying the code for a unique protein. And those genes contain billions of nucleotides that pair together to form the building blocks of DNA.

In Progeria, one of those nucleotides is a Cytosine instead of a Thymine.

That’s it. As a result of this tiny defect, a protein called Lamin A doesn’t get cleaved the way it’s supposed to and sticks to the wall of the cell nucleus. This causes the wall to become unstable, setting off a cascade of downstream events that results in the phenotype of accelerated aging.

Scientists are interested in Progeria because it offers a window into the underlying mechanisms of aging. After all, if we can figure out why exactly Progeria patients age so quickly, maybe we can beat the clock in the other direction, slowing down aging and prolonging normal lifespans.

If Viagra or Ozempic were blockbuster drugs, imagine a pill for that (or better yet, let’s not).

Of course, the full picture of aging is quite complicated and multifactorial. Genetics plays a role, but so does the environment, and reproductive strategies unique to each species. You may have noticed that smaller animals with faster metabolisms, like insects, birds, and mice, tend to have shorter lifespans than larger ones with slower metabolisms, like tortoises, elephants, and whales.

This has to do with something called the rate of living theory.

The idea is that compared to animals with slow metabolisms, those with fast metabolisms – manifested by more rapid respiration, heart rate, and muscle activity (think of the flutter of a hummingbird’s wings as it hangs in the air, or the thrumming of a hamster’s heart as you hold it in your hand) – are subjected to a higher rate of oxidative stress and other forms of cell damage.

Like the country music song says, Live fast, love hard, die young….

Viewing Progeria through the lens of the rate of living theory raises an interesting distinction between the passage of time and its effects.

It’s not that time moves more quickly in Progeria, or even that metabolism (as a surrogate for time) is any faster – Progeria patients live according to the same physical and biological clocks as the rest of us. The proof is that emotional and cognitive development in Progeria occurs normally, which is exactly what gives Kimberly Akimbo its pathos.

It’s that the cells are more fragile to begin with and break down more easily. It’s like the difference between rain falling on a building built with concrete versus one built with sand. The rain – representing time – falls down equally on both, but collapse – representing time’s effects – will occur in the one made with sand long before it will in the one made with concrete.

I don’t want to get all theoretical and skirt the point that Progeria is a uniquely tragic disease. I can scarcely imagine what it must feel like to discover that your child has Progeria – although the show gives the audience a pretty good idea.

Probably the most well-known parent of a child with Progeria was Rabbi Harold Kushner, who wrote a book borne of his experience, When Bad Things Happen to Good People. That such a horrible fate as Progeria should befall an innocent child led Rabbi Kushner to question his faith in a benevolent God (of course, he was by no means the first to do so – life and history sadly provide us with no shortage of equivalent examples).

He concluded that God must be limited – a concept called Finite God Theodicy – the idea that God does his best, but is ultimately unable to prevent all evil. In other words, God may be either benevolent or omnipotent, but not both. I personally find this theology to be kind of a cop-out, or at the very least deeply unsatisfying.

But we digress beyond the scope of this blog – if you want to talk more about that you’ll have to buy me a beer….

No discussion of Progeria as metaphor and disease would be complete, however, without mentioning The Curious Case of Benjamin Button – which is a parallel example of metaphor but not disease.

As you may remember from the short story written by F. Scott Fitzgerald, or more likely from the movie starring Brad Pitt, Benjamin Button had a condition that was like the reverse of Progeria. Inspired by something Mark Twain said about life being best at the beginning and worst at the end, Fitzgerald imagined a character who was born an old man and grew younger over time.

While Benjamin Button’s disease is not a real thing, it, too, makes for a potent metaphor. I would love to see Kimberly Akimbo and The Curious Case of Benjamin Button back to back one day. They are both poignant tales about the transience of life that make you think, feel, tear up at the end, and leave with a similar insight: It’s not what we hold onto that matters, but what we do while we are here and what we leave behind.

Dr. Bertie Bregman
Dr. Bertie Bregman
Full Stack Family Medicine is a newsletter about what it’s really like to practice medicine and run a medical practice in New York City.
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