A nonagenarian puts aging research into perspective.
"To another ninety years!" I said, toasting my grandma. My brother and I had stopped by her apartment on her birthday with a six-pack of bock beer, her favorite brewing style. Being a German Wisconsin woman, there are few things she likes better. Though I'm used to her wit and still sharp tongue, her quick reply to the toast surprised me.
"Let's hope not!" she chortled. I tensed as I felt the bottom fall out on my chest. I'd missed the mark of longevity and hit on the weariness of aging. But before I could even stammer out a response, she added with a wink and a grin, "maybe just another forty-five."
We all want to ignore the reality of aging and have our loved ones to stick around longer. Aging reveals not only the finite nature of human life, but also an increasing susceptibility to tortuous diseases such as cancer, Alzheimer's, heart disease and diabetes -- what biochemist Roz Anderson of the University of Wisconsin-Madison calls "age-associated diseases." Scientists suggest that the differences in genomes can explain the differences in lifespans seen across species. And yet studies on animals as dissimilar as yeast, worms, fruit flies and mice have all shown that genetic tinkering can extend lifespans. Taken together, the studies are slowly revealing factors that can extend an organism's lifespan.
Evolution is unlikely to have selected for the genes involved in aging, since most organisms die of starvation, exposure or predation before aging could have any effect. However, the genes could be selected for as side effect of something else. "Something else," says Matthew Piper, a geneticist at University College London, "would be growth and reproduction."
Though certainly not the explanation for Gram's longevity, one way to extend an animal's lifespan is to remove its ability to reproduce. In the nematode C. elegans, a favorite model organism of geneticists, scientists can increase lifespan by lasering four specific cells that would otherwise develop into the germ line--sperm and eggs. Removing an organism's entire reproductive system doesn't increase its longevity, says Cynthia Kenyon, a molecular biologist at the University of California-San Francisco, but taking away the cells that will become its offspring does. "Imagine an organism that has evolved under certain conditions, where sometimes the reproductive system doesn't grow as it should," she says. "If it can slow down the aging process until germ cells are ready, then the worm wouldn't go ahead and age before it had the chance to reproduce."
A 2012 study from South Korea suggests that the same effect can be seen in humans, Kenyon says. Analyzing historical records of castrated men, researchers found that eunuchs lived longer than men equipped for reproduction. The link between reproduction and aging can be seen elsewhere in the animal kingdom, she says, noting that salmon go belly up and die after spawning.
Speaking of salmon and eggs, one of my family's de facto mottos is "live to eat." Gram's recipes for banana cream pie and beef stroganoff are the best I've ever had. For us, calories are in no short supply, and yet, a short supply is one of the surest paths to longevity.
"There's overwhelming evidence that calorie restriction extends lifespan in rodents," says Roz Anderson, the University of Wisconsin biochemist. While recent data on humans and other primates hasn't shown the same effect, she says, "It's clearly beneficial for health."
Age-associated diseases --cancer, diabetes, heart disease-- are all linked to problems of with metabolism, says Anderson. Calorie restriction forces a change in metabolism, which may delay the onset of those diseases.
A severely restricted diet, however, is not something she recommends humans try. "Life is too short and pleasure is too infrequent," she says. For Anderson and other scientists, it's just a tool that allows them to see aging in a different light.
If scientists can untangle the causes and commonalities of age-associated diseases, it could help increase the quality of life during the time we do have. It's not only about extending chronological life, but also extending the healthy years, says Basil Hubbard, a molecular biologist at Harvard Medical School.
Gram would agree with Anderson, though she adds her own twist. "Life is too short to drink cheap wine," she says. Perhaps she's got the right idea?
A type of molecule which can be found in red wine has been shown to increase lifespan in animals commonly used in genetics research. Plants produce resveratrol, one of these molecules, in times of stress. This molecule seems to help them handle the stress, says Hubbard. "Organisms that feed on these stressed plants pick up the benefit."
Like a videogame power-up, resveratrol has been shown to help activate a gene associated with longevity existing in yeast and mice. Will it work in humans? "The jury is still out," says Hubbard. But a recent paper published in the journal Science, co-authored by Hubbard, shows that the power-up works on the human version of the same gene, so there's hope. Synthetic, more potent versions of these molecules are being developed to treat age related diseases. Though promising, researchers cancelled a clinical trial in 2010 testing the effects of resveratrol after several patients developed kidney failure.
As with calorie restriction, Hubbard doesn't recommend downing magnum bottles of Ch?teauneuf-du-Pape. "It would take hundreds of glasses a day to get a similar effect," he says, "and any benefit would be offset by too much alcohol."
If only Gram were as fond of red wine as she is of beer.
The science of aging is still maturing. Gram has obviously done well enough without its insights. But what if, against her wishes, I wanted her around for another 90 or 900 years? Is there anything --short of bending the laws of space and time-- that I could apply?
There is such thing as eternal life in cells. In some cases it's called cancer and can be fatal. But one other type of cell can be considered immortal. Many in genetics and aging research speak about two different kinds of cells: somatic cells and the germ line cells mentioned earlier. Somatic cells allow you to live, making up your muscles, organs, and bones. Germ cells --eggs and sperm-- allow you to reproduce.
Scientists like Kenyon, the UCSF biologist, think of the germ line as immortal. Exactly how it stays immortal is unknown and is a subject of research, but the proof is borne out every day throughout the tree of life. "If a sperm cell is used to make a puppy, or child, it grows up and has more sperm," Kenyon says. Since the combination of egg and sperm divides repeatedly to create the entire offspring, including the offspring's own germ cells, "there is lineage you can draw from one sperm to the next that never dies."
So even though Gram's somatic cells won't make it another 90 years, or probably not even 45, a part of her will. Her germ line, now carried on by my brother and me, may live even ninety times that.
Images: Grandma, photo by Author; Sperm fertilizing egg by ScienceGenetics.