A genetic discovery in worms suggests there may be molecular switches controlling lifespan and healthspan—quality of life as we age—separately.
Aging research indicates that better healthspan may be more important than lifespan.
Healthspan includes a set of parameters like mobility and immune resistance that are distinct from lifespan, which is easier to measure. In the long run, it may be more relevant to modify healthspan, even though it’s harder to study, says senior author Arjumand Ghazi, associate professor of pediatrics, developmental biology, and cell biology at the University of Pittsburgh School of Medicine and UPMC Children’s Hospital.
She uses the Greek myth of Eos and Tithonus to describe the difference: “The goddess Eos fell in love with a mortal man, Tithonus, and asked that he be granted eternal life, but forgot to ask for eternal youth. Tithonus lived forever but as a frail and immobile old man.”
Longevity gene TCER-1
As reported in Nature Communications, Ghazi and her team focused on a protein called TCER-1 in the worm Caenorhabditis elegans. Earlier work from their lab showed that TCER-1 promotes longevity in worms and also is critical to its fertility.
Longevity genes in many animals increase resistance to stressors, such as infection, so the researchers expected that removing TCER-1 would make the worms less resilient.
Much to their surprise, they saw the exact opposite. When infected with bacteria, subjected to DNA-damaging radiation, or high temperatures, worms without TCER-1 survived much longer than normal worms. They also had improved mobility with age and were less prone to protein clumping that causes human neurodegenerative diseases. Conversely, increasing TCER-1 levels beyond normal suppressed the animal’s immune defenses.
“I was sure I’d made a mistake somewhere,” says Francis Amrit, the study’s lead author and a staff scientist in Ghazi’s lab. “But I repeated the experiments and realized that TCER-1 was unlike any other longevity gene we’d seen before—it was actually suppressing immune resistance.”
Interestingly, TCER-1 seemed to be able to wield its influence only as long as the animals were young and capable of laying eggs.
“I liken TCER-1 in C. elegans to a DJ who controls the base, treble, and other tones to get the music to sound just right,” says Amrit. “During its reproductive age, TCER-1 tunes all the molecular dials to ensure that the animal reproduces efficiently to propagate the species, partly by diverting resources meant for stress management.”
How can we improve human healthspan?
Ghazi cautions that it is too soon to make any conclusions about human healthspan, but notes that the finding should change how we understand the molecular basis of aging.
“It will be interesting to understand how the body allocates resources,” Ghazi speculates. “For example, could women one day take a pill once they decide to stop having children that would improve their healthspan by diverting resources used for reproduction toward improved stress resilience?”
Additional coauthors of the study are from the University of Pittsburgh and Rutgers University. Funding came from the National Institutes of Health and the New Jersey Commission on Cancer Research.
Source: University of Pittsburgh
