Is It Time to Rethink Aging?

Medicine, history, and rare age disorders are reshaping the way researchers view the process of aging, and it may extend lives for decades.
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Medicine, history, and rare age disorders are reshaping the way researchers view the process of aging, and it may extend lives for decades.
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Every four seconds, somewhere in the world, a baby is born. Babies grow, become toddlers, teens, adults. They age, they die. It's only natural and quite straightforward. Or is it?

As it turns out, aging is not the inexorable, straightforward process we once thought it was. Our ideas of longevity and life expectancy have changed not only with medicine, but also with new views on history. And new research into rare aging disorders is revealing clues about how aging works, and whether it can be dramatically slowed down to extend lives.

For decades, some bad science perpetuated the misconception that people's lives were much shorter in the ancient times than they generally are today. For example, in 1950, Scientific American published a paper that reported that the average length of life in ancient Greece was 35 years, and in ancient Rome 32. The problem with those numbers is that they estimated an average lifespan for every member of the population, including those who died in infancy, those who died at war or from other violent causes.

In fact, when the numbers are properly adjusted to include only those adults who died naturally of old age, it appears that our ancestors lived nearly as long as we do today. Prominent philosophers, poets, and politicians of ancient Greece generally lived up to 68 years of age: Plato died at 80, Aristotle at 62. Great Italian painters of the Renaissance lived to around 63: Leonardo da Vinci died at 67, Michelangelo at 88.

Because ancient historians were more attentive to the lives of men than women, we lack sufficient data to compare gender differences in life expectancy before the 15th century. Still, over the 500 years from the late 15th to the early 20th century, life expectancy for women rose by 30 years. While men, by and large, enjoyed life well into their 70s even before the medical advances of the 20th century, women's life expectancy was dramatically affected by dangers associated with childbirth.

The other important cause of lower life expectancy, for most of history, was early childhood mortality—a figure that significantly declined as medicine improved in the 19th century. Once that factor was stripped out, an average British five-year-old boy in Victorian times was projected to live until 75 years old and an average girl until 73—comparable with today's rates of 75.9 and 81.3 years, respectively.

That said, age-associated diseases remain as common today as they were centuries ago. Twenty-four percent of elderly Americans die from heart disease, and 23 percent from cancer. So do we need to rethink the concept of aging altogether?

Investigating How Aging Works

Some researchers, like the geriatrician Richard Miller of the University of Michigan, argue that, unless scientists target the illnesses of aging holistically, we will see only very modest increases in disability-free life expectancy. Basic research into the mechanics of aging, they argue, could add healthy decades to people's lives.

Consider Jane Doe, a perfectly average, 50-year-old American woman. Based on current health risks, she would be expected to live for another 32 years. If we could eliminate cancer mortality risks at all ages above 50, it would only increase Jane's life expectancy by 2.7 years. If we could eliminate risks of death due to cancer, heart disease, stroke, and diabetes altogether, it would increase her life by 14 years.

At the same time, if we can slow down the aging process to an extent that is routinely achieved in laboratory animals, she might be able to enjoy a whopping 30 more years of life—on top of the average 82. And we aren't talking about an old age bound to bed and medicine cabinets. Ninety-year-old adults could have as active and healthy lives as today's 50 year olds.

But what about extreme cases, in which the aging process is sped up? Patients with Hutchinson-Gilford progeria syndrome, a premature aging disorder, might bear key answers to why we age, and to how we can work with nature to slow the aging down.

Clues in Disorders

Progeria is a fatal disorder, the genetic origins of which were described only a few years ago, though it has been known of since the 19th century. It's possible that F. Scott Fitzgerald drew inspiration for his short story "The Curious Case of Benjamin Button" from a real-life protagonist, a three-year-old boy with features resembling those of an elderly man, whose case was first reported in 1886. The condition is extremely rare and affects only one child out of eight million. The children are born healthy, but within a year develop signs of growth retardation, with their appearance looking increasingly more like that of an elderly person: thin skin, hair loss, arthritis, and heart complications.

To raise awareness about the condition, in January of 2013 HBO aired a documentary, Life According to Sam, about an average teenager, Sam Berns: smart and funny, he loved Legos, sports, and music. He also happened to be born with a genetic mutation in a protein called lamin A. Lamin is a key protein component of the envelope that surrounds the cell's nucleus, the compartment where DNA is stored. Research has found that a single mutation of the gene that encodes lamin A determines whether a child will develop symptoms of progeria in the first year of life.

Research on progeria is one of the many examples of how basic research can reveal important clues about how aging works. In August of 2017, cell biologist Abigail Buchwalter, from the the Salk Institute for Biological Studies in La Jolla, California, published a paper that sheds light on why and how progerin, a mutated form of lamin A, affects normal cell function. She was surprised to find that skin cells of progeria patients were making new proteins faster than cells of healthy donors.

She then showed that this rapid protein turnover was caused by increased protein production, rather than degradation. In other words, paradoxically, the aged cells (both from progeria patients and healthy elderly people) tend to work harder than the young ones, making more and more building blocks and constantly renewing the cell's machinery. What's more, when Buchwalter genetically introduced progerin into immortalized cells, she detected signs of increased protein production, establishing a more direct causal link between progerin, protein biosynthesis, and rapid aging.

"Production of proteins is an extremely energy-intensive process for cells," Martin Hetzer, a senior author of the paper, explained in ScienceDaily. "When a cell devotes valuable resources to producing protein, other important functions may be neglected. Our work suggests that one driver of both abnormal and normal aging could be accelerated protein turnover."

It's becoming more and more apparent that studying aging is a worthwhile cause. The world is getting older, and the problems of aging are becoming more urgent. Today, 8.5 percent of people worldwide are at least 65 years old. By 2050 that number is projected to double. According to the 2015 United States census, "the global population of the 'oldest old'—people aged 80 and older—is expected to more than triple between 2015 and 2050, growing from 126.5 million to 446.6 million." As the aging population expands, pressures on Social Security and Medicare will balloon too. People are living longer, but they are not necessarily living healthier.

The work on progeria is a perfect example of how studying a seemingly obscure condition could contribute to major breakthroughs that affect us all. In this case, the work gives us a glimpse into the very nature of aging—or at least one of its contributing factors. Buchwalter's observations have the potential to be used as diagnostic markers for cell aging, or even become a foundation for future discoveries, instrumental for developing life-extending treatments. Inescapably, we all know the experience of aging. Yet despite the universality of growing old, there are so many questions to answer and curiosities to uncover. Aging is weird. There's a lot left out there to learn.

This story originally appeared on Massive, an editorial partner site that publishes science stories by scientists. Subscribe to their newsletter and follow Massive on Facebook and Twitter.

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