Why do people get sick and die from old age, while some other organisms don’t? Is there a way to prevent aging in humans—or even to reverse it?
In Jellyfish Age Backwards, biotech researcher Nicklas Brendborg uses Turritopsis dohrnii—the immortal jellyfish—as an entry point to explore the latest research on longevity. Brendborg weaves together cutting-edge science, evolutionary biology, and practical insights about the topic.
Continue reading for an overview of Jellyfish Age Backwards.
Overview of Jellyfish Age Backwards
In Jellyfish Age Backwards, biotech researcher Nicklas Brendborg weaves cutting-edge medical science together with practical insights about diet, exercise, and lifestyle factors to explore how people can live the longest and healthiest lives possible.
Brendborg is a Danish biotechnologist and science writer. He earned his MA in biotechnology from the University of Copenhagen, where he researched aging and genetics. He has since established himself as a prominent voice in the fields of aging research and science communication, thanks in large part to Jellyfish Age Backwards, which was published in 2021 and quickly became a bestseller.
In this guide, we’ll present two competing theories about why we suffer the effects of old age: either our DNA suffers damage from random events throughout our lives, or we’re genetically programmed to age and eventually die. We’ll then discuss various anti-aging strategies, including lifestyle changes and medical interventions that offer hope for anti-aging treatments in the future.
The How and Why of Aging
Brendborg begins by explaining that, among humans, the damage from aging builds up exponentially: The odds of dying from age-related conditions start at practically zero, then double every eight years or so after puberty. This happens because the human body grows increasingly weak over time and eventually succumbs to something like heart failure, cancer, infection, or injury.
However, Brendborg notes that the aging pattern he describes doesn’t hold across all of nature. Some creatures, like the aptly named immortal jellyfish, can reverse their aging—hence the book’s title, Jellyfish Age Backwards. Naturally, this raises the question of why humans age the way we do, rather than being able to rejuvenate ourselves like this jellyfish can.
Brendborg says that understanding how and why aging happens is crucial for developing effective treatments for it. In this section we’ll present two theories: aging as accumulated DNA damage, and aging as a genetically programmed process.
Theory #1: Aging as Genetic Wear-and-Tear
The first theory Brendborg discusses is that aging may be the result of genetic damage accumulating over time. During cell division (mitosis), DNA must be precisely replicated to ensure that the new cell has all of the correct genes. However, mitosis is complex, and errors frequently occur during the process. These errors are known as mutations, and they can cause cells to work less effectively or stop working altogether.
While many mutations are caught and corrected during mitosis, and others trigger defense mechanisms that destroy the mutated cell, some are bound to escape the body’s protective measures. So, according to this theory, as cells continue to divide throughout a person’s lifetime, mutations accumulate in their DNA and cause the symptoms of aging: frailty, fatigue, a weakened immune system, and so on.
Theory #2: Aging as “Planned Obsolescence”
Brendborg says it’s possible that aging isn’t the result of random mutations. He discusses a second theory, which holds that we’re genetically hardwired to age and die.
DNA Methylation Causes the Body to Break Down
The theory that aging is programmed into our genes emerged from the discovery of methylation: the process of molecules called methyl groups accumulating in DNA over time. These methyl groups attach to the epigenome—the parts of the DNA next to genes—and interfere with those genes’ functions.
Notably, researchers have found that methylation follows predictable patterns across different tissue types and even among some different species. It’s much too consistent to be the result of random DNA damage, which is why Brendborg says humans may be genetically programmed to age: The consistency of the pattern suggests that DNA methylation is a natural part of our life cycle, just like growing from an infant to an adult.
This discovery led to the creation of a test called the epigenetic clock, which can estimate the age of an organism by measuring the degree of methylation in its DNA. Furthermore, studies have shown that people whose epigenetic age is higher than their chronological age—in other words, people whose DNA is more methylated than normal for their age—face increased risks of early death and age-related diseases. The reverse is also true: People with lower levels of methylation than normal tend to live longer, healthier lives.
Telomeres Limit the Body’s Ability to Heal
While Brendborg mostly focuses on DNA methylation, he also presents another piece of evidence that old age might be programmed into human genetics: Parts of DNA known as telomeres place inherent limits on the body’s ability to regenerate itself.
Telomeres are specialized structures at the ends of each chromosome (strand of DNA). They’re long strings of repetitive, meaningless DNA sequences that work like the plastic tips on shoelaces, holding the DNA together so it doesn’t unravel. They also act as a buffer, protecting the useful DNA in the genes from damage.
Telomeres become slightly shorter each time a cell divides and eventually reach a critical length where the cell cannot safely divide again. Brendborg explains that a cell that can’t divide anymore enters a state called senescence, where it stops performing most of its intended functions, but doesn’t get destroyed by the body’s defense mechanisms like usual. Furthermore, senescent cells (informally called “zombie cells”) start releasing chemicals that damage the tissues around them, thereby causing the aches and pains associated with old age.
Lifestyle Strategies to Combat Aging
Now that we’ve discussed two competing theories of aging, we’ll explore the various methods Brendborg suggests for slowing (and, in a few cases, reversing) the aging process. Brendborg emphasizes that aging is complex and involves many different mechanisms, so it’s unlikely that any one method will be enough to combat it. Therefore, the most effective approach to anti-aging is to use multiple different strategies to treat the symptoms of aging and keep the body strong for as long as possible.
The first strategies the author presents are lifestyle changes you can make to extend your years of life and health. The methods we’ll discuss in this section fall into three categories:
- Dietary restrictions
- Using healthy stressors (such as exercise) to strengthen the body
- Mental and emotional care
Dietary Restrictions
The first lifestyle strategies that Brendborg discusses have to do with eating habits. He says that you can dramatically improve your health and lifespan by strictly limiting either how much you eat or how often you eat.
Strategy #1: Calorie Restriction
Brendborg begins by discussing calorie restriction: dramatically reducing how much you eat.
He says that, based on various studies and observations, people who have cut their calorie intake by anywhere from around 10-25%—while still making sure to get all the nutrients they need—have shown remarkable health improvements. Some of the benefits include losing weight, reduced blood pressure, and improved immune responses.
However, by their very nature, such studies take a long time to conduct. Therefore, it’s too soon to say for sure whether calorie restriction ultimately leads to a longer lifespan in humans.
While there isn’t yet a consensus about whether calorie restriction makes you live longer, Brendborg says that researchers do have theories about the health improvements they’ve recorded so far. Calorie restriction appears to trigger various cellular maintenance mechanisms, most notably autophagy.
Autophagy, which literally means “self-eating,” is the body’s way of breaking down damaged or mutated cells and recycling their components. This is not just an efficient use of resources, it’s also a way for the body to repair itself. This cellular recycling process is sort of like repairing a machine by swapping out damaged components for new ones. Although autophagy happens naturally throughout your life, it declines as you get older. Promoting autophagy through calorie restriction (or other methods, as we’ll discuss) seems to counteract this decline, which may help you maintain healthier cells into old age.
Strategy #2: Intermittent Fasting
Brendborg notes that severe calorie restriction is an unrealistic approach for most people—they’d find that any benefits to their health and lifespan aren’t worth the discomfort of constant hunger. However, intermittent fasting (IF) may offer similar benefits while being much more sustainable for the average person.
IF is a dietary strategy that limits when you eat, rather than how much you eat. For example, common methods include setting an eight-hour window each day during which you’re allowed to eat (say, between 9:00 am and 5:00 pm), and alternate-day fasting: eating normally one day, then eating little or nothing the next day, and repeating that pattern indefinitely.
According to Brendborg, recent research has suggested that the life-extending benefits of calorie restriction may actually be due to longer periods of fasting between meals, rather than eating fewer calories overall. In other words, autophagy and other maintenance processes trigger after you go for a long enough time without eating, even if you still eat the same amount of food overall.
Healthy Stressors
The second lifestyle strategies Brendborg shares have to do with healthy, positive forms of stress—mild hardships that strengthen the body instead of weakening it. In biology this is called hormesis: a phenomenon wherein small amounts of a stressor can be beneficial, while larger amounts of that same stressor are harmful or even fatal.
To give an example, many medicines follow this pattern. Taking the recommended dose of, say, a cough medicine will produce the intended effects (clearing up congestion and relieving your cough), but taking too much could make you seriously sick.
Strategy #1: Exercise
The most obvious form of healthy stress is exercise, and the fact that exercise helps you live longer is hardly a new discovery. However, Brendborg emphasizes that the health and longevity benefits of exercise seem to have no hard limits. This means that, regardless of your age or your fitness level, working out will continue to boost your health and lifespan.
Brendborg explains that more exercise is better as a general rule, but it’s crucial to remain aware of how your body feels and performs. Remember: Exercise is a form of stress, meaning it actually hurts you. The health benefits of exercise come from the recovery period, when your body rebuilds itself to be stronger than it was before. And while the benefits of exercise have no limits, there is a limit to how much your body can handle. If you overwork yourself, you’ll reach a point where the damage outweighs the benefits—for example, you might tear a muscle by trying to lift weights that are too heavy for you. So, if you’re in pain or find that you seem to be getting weaker instead of stronger, it’s probably time to rest and recover.
Strategy #2: Plant Compounds
Brendborg says that another way to benefit from hormesis is to take advantage of the natural defense mechanisms found in many edible plants. Much like the benefits of exercising, the health benefits of fruits and vegetables have been common knowledge for a long time, but most people assume these plants are valuable because they’re nutritious.
However, some scientists (including Brendborg) think hormesis also plays a role in their value. For example, pineapples contain an enzyme that breaks down proteins, which is why your mouth might feel strange after eating it—the enzyme isn’t dangerous enough to harm humans, but it may induce hormesis. Similarly, most fruits and vegetables contain compounds called polyphenols that are mildly toxic to humans; the relatively small amounts you ingest won’t hurt you in any noticeable way, but the author says that it’s still enough to trigger hormesis.
A Warning: Other Kinds of Hormesis Are Too Risky
Brendborg acknowledges that exercise and eating your vegetables might not be new or exciting ways to extend your life, but they’re effective and safe. He then discusses a couple of other possible ways to become stronger and more resilient through hormesis—however, he insists that these are too dangerous to try. He explains that hormesis is dangerous by nature, and it’s very easy to do more harm than good. Additionally, there’s no ethical way to conduct studies that involve intentionally hurting people. Therefore, the methods he discusses have never been rigorously tested for safety or effectiveness in humans.
With that said, two other possible ways to induce hormesis include:
1) Poisons: Brendborg discusses studies performed on roundworms, where researchers found that low doses of arsenic (a deadly poison) and paraquat (a powerful herbicide) actually extended the worms’ lifespans. The test subjects also became more resilient against other toxic substances. However, higher doses of those poisons killed the roundworms, as expected.
2) Radiation: Studies of radiation exposure, such as accidental exposures among nuclear plant workers, have shown that low doses of radiation can produce unexpected health benefits. Some of these benefits included lower cancer rates and longer average lifespans among those exposed.
Medical Strategies to Combat Aging
We’ve discussed lifestyle changes that you can do on your own to improve your health and extend your lifespan. In this final section, we’ll go over some medical interventions that hold promise for treating the symptoms of old age—or even reversing the aging process.
Strategy #1: Medications
Brendborg starts by discussing various drugs that may be able to slow the aging process.
The first of these drugs is metformin, a diabetes treatment that has shown promise for extending a person’s life even if they are not diabetic. This is because insulin resistance tends to increase with age, meaning your body gets less efficient at processing sugar, and therefore is less able to regulate your blood sugar levels. Insulin resistance is the exact problem that drugs like metformin are designed to treat, meaning that this could be a way to treat one of the symptoms of aging.
However, Brendborg is somewhat skeptical about giving metformin to healthy people because it may make exercise less effective, which is counterproductive to a long and healthy life. Exercise and metformin both boost your ability to metabolize sugar, but for reasons that scientists don’t fully understand, these two methods seem to interfere with each other rather than supporting each other as one would expect.
There are also drugs that promote autophagy, the cellular recycling mechanism we discussed in the Dietary Restrictions section. Remember that autophagy naturally declines with age, so enhancing it (using dietary choices, medications, or both) is an effective way to combat that part of the aging process.
One of these autophagy-boosting drugs is rapamycin, an immunosuppressant that’s normally used to prevent the body from rejecting a transplanted organ. Another is spermidine, a compound found naturally in many foods like whole grains and legumes. Spermidine has the advantage of not needing a prescription, since it’s readily available as a dietary supplement.
Finally, Brendborg points out that the development and testing of anti-aging drugs faces significant challenges. This is because, by the very nature of the work, it takes a long time to determine whether anti-aging treatments have been effective. Researchers must either wait decades to see if middle-aged test subjects live longer than expected, or test drugs on elderly subjects with less time for the treatments to work.
Strategy #2: Cellular Engineering
If aging is the result of changes to the DNA, as the theories we discussed earlier suggest, then the best way to reverse aging would be to undo those changes at the cellular level. In fact, Brendborg says that scientists have already discovered a couple of ways to do this. Unfortunately, both of these methods greatly increase the risk of cancer, and there’s currently no safe way to use them on people.
The first method is telomerase activation. Recall our earlier discussion of telomeres, the protective DNA caps that get shorter each time a cell divides. An enzyme called telomerase is able to rebuild those telomeres, so boosting telomerase could let cells avoid senescence and keep dividing forever.
Brendborg says the second method uses a set of four genes, which are called Yamanaka factors after the scientist who discovered them: Shinya Yamanaka. Researchers have used the Yamanaka factors to revert adult cells to embryonic stem cells, literally resetting those cells’ biological clocks. They can then regrow into young, healthy cells of any type.
Exercise: Gather Your Thoughts About Aging (and Anti-Aging)
- You’re now familiar with Brendborg’s theories about why we age and what we can do about it. Now, take some time to consider your own ideas about aging, and how you might extend your life and years of health.
- Did anything you learned about the aging process or anti-aging treatments surprise you? If so, what was it?
- Which of Brendborg’s anti-aging strategies could you start using in your daily life? For example, perhaps you’d like to start exercising regularly, practicing intermittent fasting, or trying a dietary supplement like spermidine.
- If a safe and effective “cure” for aging were developed—for instance, if doctors learned how to use Yamanaka factors without the risk of cancer—would you take it? Why or why not?
