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When I first started investigating life extension as a spanner—or non-PhD layperson interested in lifespan and healthspan—I quickly became overwhelmed.
The heck is NAD+ and rapamycin? Isn’t cryonics something from science fiction? Mitochondria are “mighty,” I recalled from high school biology, but what on earth do they have to do with metabolism or aging?
While the science behind life extension research can be exciting, the jargon surrounding such research is so confusing that it can make you want to dismiss it outright, even if it’s describing a really exciting breakthrough. People just want to understand what they’re reading and why it matters.
That’s where this list comes in. Scientists in fields related to life extension often assume that their readers already have advanced degrees in medicine and biology, but that often isn’t the case. Deciphering life extension literature is often like trying to learn a new language. We created this list to help “translate” some common terms used to describe anti-aging (excuse me, “geroprotective”) breakthroughs.
Let’s get into it.
The longevity glossary
This expanding list of longevity-related terms aims to give a primer on common life extension concepts. If you know each of these terms, let us know in the comments what should be added to the list. If not, this glossary will give you the 101 on the ever-expanding lexicon you need in order to understand life extension research.
We will continue to update this list as we expand the site.
Aging might seem like an obvious thing: you get older and then you die. But the word “aging” isn’t that simple. It actually refers to a very specific biological and metabolic process in living organisms.
Aging in humans is the process of gradual decline of physical and psychological functions correlated with old age. “Aging” is often a term used metaphorically (“he aged overnight”) or as shorthand for the effects of age-related diseases (“I forgot where my keys are again! I must be aging.”), so spanners tend to focus on senescence—or biological aging.
Have you ever taken an online quiz to find out your “real” age? (RealAge is the most popular of these tests.) Or watched a TV conversation with a doctor that went something like, “You might be 45, but you have the body of a 65-year-old!” Those real age tests are not referring to your chronological age—that’s set from the day you were born—but your age according to your health markers. Biological aging refers to the set of aggregated metabolism processes that leads to cellular damage, waste, decay, and imperfections over time. The field of aging science has pretty much agreed on 8-9 different “hallmarks of aging” that universally define biological aging, such as the body’s loss of its ability to create new stem cells.
While nobody can change their chronological age, biological age is malleable. Interest in biological aging correlates with extending healthspan, or the years of your life when you are healthy and uninhibited by the consequences of biological aging. If you can extend your healthspan (even if your overall lifespan remains the same) your quality of life will vastly improve.
Autophagy is something that’s often discussed alongside intermittent fasting for longevity. It’s from Greek, meaning “self-eating.” Autophagy is a metabolic process in which cells “eat” and recycle parts of themselves that are malfunctioning. Nature explains that it’s “cellular housekeeping, during which dysfunctional organelles, misfolded proteins, or pathogens are removed or degraded.” Cells then reuse some of the metabolites.
Autophagy is often confused with apoptosis. Apoptosis is a normal part of tissue development—it occurs in cases where the cell chooses to kill itself (often called “programmed cell death”) if it can’t otherwise save itself from becoming damaging to the body.
Autophagy dysregulation is associated with cardiovascular disease, Alzheimer’s disease, and muscle loss.
Autophagy isn’t all good though. For example, autophagy can both treat and exacerbate cancer. It can limit wound healing as well. We don’t yet know how to measure autophagy effectively in humans.
Biogerontology is the study of biological aging with a particular focus on possible measures to slow or stop biological aging and age-related diseases. Biogerontology is often referred to in contrast with gerontology, which focuses on the management and care of people who are already old and frail.
Famous biogerontologists include Aubrey de Grey, Cynthia Kenyon, and Michael R. Rose.
4. Chronic Inflammation
Inflammation is an immune response against harm. It’s sometimes visible, like red swelling around a scraped knee, and sometimes not, like gut inflammation after eating way too many french fries. Inflammation, in its acute form, is more often good than bad—it’s your body’s natural healing response after it perceives something is trying to harm it.
However, inflammation is supposed to go away after a few hours or days, depending on the severity of the injury. If it doesn’t dissipate, the body experiences chronic inflammation. In this state, the immune system remains active and alert, which can have significant consequences. For example, one study from the Newcastle University’s Institute for Ageing and Keio University School of Medicine found that inflammation markers may be better indicators of a longer lifespan than telomere length. Other studies have tied chronic inflammation to age-related diseases like diabetes, Alzheimer’s, and cancer.
Cryonics (not to be confused with cryogenics) is the practice of freezing the recently deceased so that they can be revived at a later date.
Cryonics isn’t based on science fiction; consider the incredible case of Anna Bågenholm, who in 1999 survived for 80 minutes under icy water—long enough to be found and resuscitated—because the cold slowed her metabolism and brain function enough to require less oxygen than an aware, active person. The idea is that people today could be preserved long enough for medical technology to develop that can cure whatever “killed” them in the present.
There are few cryonics companies accepting “members” at this time. Notable U.S.-based companies include Alcor, the Cryonics Institute, and Osiris.
Every Halloween, my friends and I go out to see an 80s cover band called The Legwarmers. They use the same instruments, tempo, and music score of all the greats, and their vocalists give incredible impressions of The Bangles, Journey, and Bon Jovi. But they don’t quite sound the same as the original tracks—they hold some notes longer, they take breaths at different beats—and some of it is purposeful, and some isn’t. After all, it’s a Legwarmer’s cover. Similarly, every production of Romeo and Juliet has its differences, in spite of using the same characters and original script. There’s room for interpretation by the performers.
That interpretive spirit is the role of the epigenome when reading DNA sequences—think of DNA like the sheet music or script for a cell, and the epigenome like the conductor or director for how its instructions are carried out. The epigenome is made up of all the chemical compounds that have been added to one’s genome to regulate its gene expression. Its Greek root, “epi-,” means “over” or “upon;” the epigenome is not a part of the genome, but it is attached to it. Environmental influences, like stress levels, diet, and pollutants, inform how the epigenome “activates,” or interprets, one’s genes. These genetic interpretations can vary down to a single cell or can change an entire body.
Epigenetic changes can influence everything from muscle tissue growth to estrogen or testosterone production—it’s a neutral bodily function. However, there are sometimes errors in the epigenetic process which can have severe consequences. Cancer, metabolic disorders, and degenerative disorders can all be traced back to epigenetic mistakes.
Epigenetics are also the basis for measuring biological age.
7. Genome editing
Genome editing manipulates the genes of a living organism for certain desired outcomes. For example, crops like potatoes and barley have been genetically modified to be resistant to bacterial blight, and some cattle have been altered to become naturally hornless, doing away with the inhumane but often necessary practice of dehorning calves as they age.
Scientists have successfully used genetic modifications to increase the lifespan of nematode worms, fruit flies, and mice.
CRISPR, short for “clusters of regularly interspaced short palindromic repeats,” is an oft-referenced tool for genome editing. It’s so widespread and deregulated that you can order a CRISPR kit for use at home. CRISPR can be used to tweak genes in any plant or animal, and it’s currently being used in clinical trials to combat cancer.
Homeostasis is the body’s process of self-regulating its biological systems. For example: if you’re hot, you sweat to cool yourself down. If you’re cold, you shiver to warm yourself up. You feel hot or cold, which motivates you to change your condition (like put on a sweater or drink a glass of cool water). It’s an automatic system that keeps your body regulated.
Homeostatic capacity is the ability to recover from stressors—like returning to a normal temperature after being too hot or too cold.
One major theory of why aging is so deadly is that maladies associated with aging can disrupt one’s homeostatic capacity, eroding the body’s ability to keep itself regulated.
9. Longevity Escape Velocity (LEV)
Coined by David Gobel, co-founder of the Methuselah Foundation, and made famous by Aubrey de Grey and Ray Kurzweil, Longevity Escape Velocity is a future, hypothetical situation where, for every year you’re alive, longevity research extends your life expectancy by another year. For example, if in 2040 you are 110 but there are technological advances that can increase life expectancy to 120, and by 2050 there are then new technological advances that increase your life expectancy to 130 (and ad infinitum), the need for the concept of “life expectancy” will disappear completely.
Metabolism is a term used to describe the sum of chemical reactions within the cells of living organisms that provide the body with energy. Ironically, the effects of metabolism both sustain and end life, the latter due to waste and cell damage accumulated during the metabolic process when the natural use of energy produces things like dangerous free radicals. In fact, one theory of aging suggests it is primarily our own internal metabolic processes that lead to the damage which results in aging.
mTOR, or the mammalian target of rapamycin, is a protein responsible for muscle tissue construction and repair. Sirolimus, a drug derived from a bacteria called Streptomyces hygroscopicus and commonly referred to as Rapamycin or Rapamune, has been confirmed to increase lifespan in mice by inhibiting mTOR functions.
There are two natural things that can activate mTOR: insulin and intense exercise.
mTOR and AMPk (or “AMP-activated protein kinase”) both regulate metabolic function. mTOR is responsible for tissue creation (think muscle building). Slow-growing animals tend to outlive fast-growing animals (elephants live longer than dogs, and both live longer than hamsters). Some scientists theorize that mTOR inhibition may also help humans live longer as well.
AMPk responds to anything that lowers ATP (the molecule cells use to store and use energy), like exercise. It does lots of great stuff for our bodies, like improving insulin resistance and lowering inflammation.
People interested in longevity tend to want to balance mTOR and AMPk, aiming to activate mTOR during exercise and otherwise prioritizing AMPk.
Sarcopenia is a progressive medical condition in which there’s a significant loss in skeletal muscle mass. It is a disease that strongly correlates with age. People with sarcopenia tend to have physical disabilities, lack autonomy, and are at a much higher risk for falls. More than half (53%) of people over 80 years old have sarcopenia.
One of the things many spanners try to balance with longevity regimens is how often to activate mTOR to maintain and grow muscle mass and prevent sarcopenia, while also minimizing the pro-aging effects of mTOR activation over the long run.
Cellular senescence occurs when old cells stop dividing but don’t die off. Commonly called “zombie cells,” senescent cells remain active in the body, throwing off dangerous proinflammatory signals to nearby healthy cells.
Though senescent cells are helpful for repairing damaged tissue, they are a net negative for the body. Senescent cells can exacerbate cancerous tumor growth, contribute to age-related brain degeneration, and lead to frailty in older individuals. The more senescent cells you have, the likelier you are to be biologically older.
Longevity researchers are currently studying a class of molecules called senolytics (like fisetin, found in small amounts in strawberries) which may selectively target and kill senescent cells and so possibly extend lifespan.
Sirtuins, named after the “SIR2” gene in yeast, are a kind of protein that regulates cellular health—they’re a key part of human homeostasis. Sirtuins function using NAD+ (nicotinamide adenine dinucleotide), an enzyme found in living cells.
There are seven sirtuins in each cell: three in the mitochondria, three in the nucleus, and one in the cytoplasm.
Think of sirtuins like the conductor of an orchestra. The cell’s parts are the musicians making up the ensemble. The NAD+ is like sheet music—without it, the conductor has little ability to direct the orchestra in what way it should play. NAD+ declines with age, so as this “orchestra” (or cell) gets older, it does not play as well as it did prior.
Sirtuins work to remove acetyl groups from other proteins. It’s like eye contact from musicians, letting the conductor (sirtuins) know that it’s okay to “activate” them.
Sirtuins were only discovered in the 1990s, so there’s much to learn about them. They are relevant to longevity because sirtuin genes have correlated with longer lifespans in yeast and male mice.
Every time a cell divides, it copies over its chromosomes. Those copies are imperfect as the very end of each chromosome cannot be copied perfectly. Telomeres protect the DNA in your chromosomes from damage during this process, capping the ends like a print bleed. Every time a chromosome is duplicated, its telomeres shorten. The rate at which an organism’s telomeres shorten is an indicator of its overall lifespan.
Which terms should we add to the longevity glossary?
Our short list of anti-aging vocabulary words is hardly complete. What do you think belongs in a primer? Where should we expand? Was this list helpful to you? Let us know how we can improve in the comments!