Why does human health decline as we age? Do all creatures age in the same way?
Biotech researcher and author of Jellyfish Age Backwards, Nicklas Brendborg, explains the top two theories on human aging: genetic wear-and-tear and planned obsolescence. However, he notes that these aging patterns don’t hold true across all of nature.
Read below to learn more about human aging process theories.
The How and Why of Human Aging
Brendborg begins his discussion on how and why we age 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.
(Shortform note: Many people, like Brendborg, talk about aging as a natural process that makes you vulnerable to diseases and injuries—the “age-related conditions” mentioned above. However, in Lifespan, biologist David Sinclair says that old age itself is the disease, and conditions like arthritis, frailty, and dementia are just symptoms of it. Sinclair adds that old age has many similarities to cancer—the most important similarity being that both diseases used to be untreatable, but modern medicine is constantly getting better at treating them.)
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.
(Shortform note: The immortal jellyfish regenerates itself through a process called transdifferentiation, wherein a fully developed cell becomes a different kind of cell. The jellyfish uses this process to revert to its adolescent form (a polyp), from which it regrows into a healthy adult. This would be like if you could turn back into a teenager at will, regaining all the strength and energy you had back then.)
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.
| The Three Types of Mutation In simple terms, a mutation is a change to the instructions encoded in your DNA. In the vast majority of cases, these changes have either no effect or a detrimental effect—hence the theory that mutations building up in your DNA over time eventually causes your body to weaken and break down. There are three kinds of mutations: 1. A silent mutation has no effect; despite the change to the instructions in your DNA, your body still functions the way it usually would. It’s like replacing one word in a sentence with another word that means the same thing. For example, ”I’m driving to the store” becomes “I’m going to the store.” 2. A missense mutation swaps out one instruction in your DNA for another, which tends to make affected cells less effective at their tasks. For example, in sickle cell anemia, a missense mutation causes red blood cells to become deformed and rigid, making it more difficult for those cells to carry oxygen throughout the body. Again, imagine replacing one word in a sentence, but this time you replace it with something that changes the meaning—“I’m driving to the store” becomes “I’m dancing to the store.” 3. A nonsense mutation happens when the DNA’s instructions get cut off early, causing the cell to lose some kind of function. For example, in cystic fibrosis, a missing or nonfunctional protein in the cell membrane prevents moisture from passing through and entering the lungs. As a result, mucus that would normally get cleared out of the lungs becomes too thick and sticky to expel. A nonsense mutation is like replacing a word in a sentence with a period, so “I’m driving to the store” just becomes “I’m.” |
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.
