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December 2, 2019

Do we have to age and die? Here's what science says.

Daily Briefing
    Editor's note: This popular story from the Daily Briefing's archives was republished on Sep. 28, 2022.

    Early research supports the theory that humans age as a result of primeval genetic mechanisms intended to regulate and repair our aging cells. But could there be ways to "turn off" these mechanisms to slow or even reverse aging? David Sinclair and Matthew LaPlante dig into the science in the Wall Street Journal.

    The best resources to guide your precision medicine strategy

    Why we age, according to an emerging theory

    New developments in the field of epigenetics are changing our understanding of the genetic underpinnings of aging.

    Sinclair, a professor of genetics at Harvard Medical School, and LaPlante, an associate professor of journalism at Utah State University, describe epigenetics using the metaphor of a piano. "If you think of your inherited genetics, your DNA, as a piano keyboard, then epigenetics determines how the keys play music," they write. "The primary players in this concert are molecular substances that affix to our genome and leave markers."

    These epigenetic markers determine how genes function—essentially turning them "on" and "off"— and they are a crucial way that our bodies regulate themselves. However, as numerous markers accumulate over time, they can create "epigenetic noise," as Sinclair and LaPlante write, which can cause cells to become dysfunctional.

    Researchers have discovered in recent years that the number of epigenetic markers acting on a person's cells can provide a surprisingly accurate measurement of his or her age. Now, a new "information theory" is growing in prominence, claiming that epigenetic markers may not just help us measure age—but that they may actually cause the decay associated with the aging process.

    Essentially, once a cell suffers from too much epigenetic noise, the theory claims, it becomes senescent and stops reproducing. This has a cascading effect on all adjacent cells, Sinclair and LaPlante write, causing the proliferation of symptoms that we associate with aging.

    Elements of this theory have been demonstrated in research on mice. When Harvard Medical School researchers altered young mice's genomes by adding epigenetic accretions, the mice experienced accelerated muscle and bone mass loss, began turning gray, experienced vision problems, and became more easily confused. In essence, they physically got older, even when they were chronologically still young.

    Epigenetic mechanisms evolved in some of the earliest life forms on earth to regulate and repair cells that aren't functioning properly. However, if the information theory is true, these same mechanisms are paradoxically what cause us to suffer from aging.

    Do we need to age?

    "[T]here is no law of biology that says we must age at the rate at which we do now," Sinclair and LaPlante write, adding that some other forms of life don't age like humans do. For instance, the bristlecone pine doesn't appear to experience aging and can survive for 5,000 years.

    Even in humans, some portion of our epigenetic markers are due to unhealthy behaviors, such as a poor diet or overexposure to the sun. While ending these behaviors will slow deterioration, scientists believe there may be other ways to "reboot" a cell to fight, or even reverse, cellular aging.

    In a 2016 study published in Cell, researchers at the Salk Institute in San Diego found they could extend the lifespans of mice suffering from premature aging by almost a third. The trick? They transiently turned on four genes that can eliminate accumulated epigenetic markers and induce "pluripotency," or the ability of a cell to develop into other adult cell forms, Sinclair and LaPlante write.

    Similarly, researchers at Harvard found that giving elderly, blind mice a combination of three genes over three weeks, and then turning on these genes using epigenetic markers, rejuvenated their optic nerves and restored their vision.

    Could epigenetic marker-based medicines work on humans?  

    Sinclair, together with Juan Carlos Belmonte from the Salk Institute and Steven Horvath at UCLA, has developed a company aiming to develop medicines for eye diseases based on their research. However, Sinclair and LaPlante caution that "there is a great distance between what can be done with mice in a lab and what can be done to help humans fight diseases and extend their healthy years."

    Sinclair and LaPlante also write that "healthy" is the operative term. "You would be hard-pressed to find anyone who thinks it would be a good idea to lengthen human lives if we cannot substantially improve the part of life that is lived free of debilitating diseases," they write.

    Their early work in humans holds some promise. The researchers published a small study in which they gave nine patients a mix of three molecules: growth hormone; DHEA, a steroid; and metformin, an anti-diabetic medication that has been shown in preliminary research to slow cellular aging. They found that the patients experienced an epigenetic age reversal, losing two years off of the biological ages of their cells.

    Sinclair and LaPlante write that there was no control group, and the results should be considered preliminary until larger, more rigorous studies take place. "But it is no longer completely crazy to talk about having birthdays in reverse," they write (Sinclair/LaPlante, Wall Street Journal, 10/25).

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