A new study published in the journal Science provides insight into the genes that influence lifespan as well as the benefits and drawbacks of living longer.

All around the Pacific Rim, you’ll find rockfish on your dinner plate — and it’s usually just referred to as “rockfish” or “red snapper”—with little care for its origin or which of the 137 species is on your plate.

However, this seemingly enigmatic fish, which is one of the longest-living vertebrates on Earth, reveals clues to the genes that control lifespan and the benefits and drawbacks of living longer.

Biologists from the University of California, Berkeley compared the genomes of nearly two-thirds of the rockfish species found in coastal waters around the Pacific Ocean and discovered some of the genetic differences responsible for the wide range of lifespans among them in a study published this week in the journal Science.

A few species of rockfish, such as the brightly colored calico rockfish (Sebastes dallii), survive for less than a decade, while others, like the rougheye rockfish (Sebastes aleutianus), can live for more than 200 years in cold, deep coastal waters.

It’s one of the most fast radiations among fishes in terms of phenotypes, which include a wide variety of lifespans, as well as a wide range of sizes, lifestyles, and ecological niches.

To uncover the genetic determinants of lifespan in rockfish, the researchers obtained tissue samples — and occasionally tasting samples — from 88 species and sequenced their complete genomes with a state-of-the-art technique known as Pacbio, or SMRT, sequencing.

In order to find the genetic drivers of lifespan in rockfish, the team collected tissue samples from 88 species and sequenced their genomes using Pacbio, or SMRT, sequencing.

However, they discovered a number of genes that are connected with long life, some of which are associated with adaptations to living at deeper depths and growing larger. Elephants, for example, have a longer lifespan than rats among mammals.

Additionally, the findings show the downsides of living long lives: fewer populations, as shown in animals when short-lived rats outweigh the more long-lived elephants.

“In this study, we identified both the genetic causes and consequences of adaptation to extreme lifespan,” says senior author Peter Sudmant.

“It’s very exciting to be able to look at a group of species and see how their phenotype has been shaped through time and the genetic changes that drive that phenotype, and simultaneously, how that phenotype then feeds back and influences the genetic diversity of that population.”

Even though many of the biochemical pathways Sudmant and his team discovered to be connected with lifespan have already been identified in genetic studies of variation within a single animal species, this study did identify numerous additional genes in these pathways. This one fish species has spread throughout the Pacific Ocean because of the wide range of genetic variations that exist within the species.

“You could think of rockfish as sort of the perfect storm. in some ways, both on an individual level — having individual fish able to live for a really long time because of size and depth adaptations — but also just having all these different species that are showing these different trends,” he adds. “They’re a perfect set of individuals to look at, where other people just had a single species to look at.”

The study’s findings could potentially help us better comprehend the lifetime of humans. In contrast to shorter-lived animals, those with a longer lifespan have more immune regulating genes, such as a family of genes known as butyrophilins, according to Sudmant and his colleagues. These findings suggest genes that could be therapeutic targets for slowing age-related damage in the body, because the immune system is engaged in regulating inflammation and increased inflammation has been implicated in human aging.

“There is an opportunity here to look in nature and see how natural adaptations have shaped lifespan and to think about how those same sorts of genes are acting in our own bodies,” according to the author.

Fish with longer lifespans have a higher prevalence of 137 longevity-related gene variants discovered by researchers.

Indirect effects on lifespan are possible, but not universal. Despite the fact that the genetic mutations that allow rockfish to grow larger and adapt to deeper depths have the unintended effect of increasing lifetime, the researchers took care to separate out these genetic variants. For example, animals that live in colder, deeper waters have a longer lifetime because their metabolism is slowed.

“We can explain 60% of the variation in lifespan just by looking at the size at maturity and the depth at which a fish lives,” says Sudmant. “So, you can predict lifespan with pretty high accuracy just from these factors. This allowed us to identify the genes that allow them to do those things.”

The rest of the longevity-related variation was mostly made up of three categories of genes: an increase in the number of genes involved in DNA repair, changes in several genes that regulate insulin, which has long been recognized to influence lifespan, and an increase in genes that modulate the immune system. More DNA repair genes may help in the prevention of cancer, whereas more immunological genes may help in the prevention of infections as well as cancer.

“Six different members of the insulin signaling pathway are under selection in these fish,” Sudmant adds. “If you look at the textbooks, there’s about nine or 10 core members of the pathway, so the majority of them are under selection in rockfish.”

Essentially, certain rockfish species increased their longevity merely by adapting to dwell in deeper, colder waters and becoming larger, according to Sudmant. The longest-living animals, on the other hand, increased their lifetime by modifying their DNA repair, insulin signaling, and immune-modulation genes.

The researchers were also able to predict what the ancient rockfish genome looked like and how species arose from that common ancestor 10 million years ago using the 88 rockfish genomes. They discovered that as people lived longer, population levels fell. Some of the world’s oldest species are still around today in small numbers, relying on very elderly, yet very fertile, females to keep the population going. The majority of progeny — sometimes in the millions every year, though with a low survival rate — that seed the next generation are produced by these large, old, fat, fecund female fish, or BOFFFF, as they are called in fish conservation circles.

“In these rockfish, we can actually watch this evolution happening over this 10-million-year time period, and we observe that when some species evolve a short lifespan, their population sizes expand, and when they evolve a long lifespan, their population sizes contract,” he explains. “We can see a signature of that in their genomes, in the genetic variation that exists in these species. So, there is a consequence to adapting to long and short life.”

Long-lived species have an excess of certain types of DNA mutations, such as the conversion of the nucleotide pair CG (cytosine-guanine) to TG (thymine-guanine), which are known to accumulate in tumors with aging, according to him. These odd genetic changes are handed down to the remainder of the long-lived population because the oldest females of these long-lived species generate the majority of the children.

Sudmant and his colleagues are currently comparing genomes of bats, primates, and other creatures to see which genes are linked to lifespan, aging, stress, and other phenotypic variations. The rockfish project, on the other hand, was unique, he adds.

“Often, in genetics, we’re derided for doing experiments that are fishing expeditions,” he said. “This was both literally and figuratively a fishing expedition.”

Image Credit: iStock

You were reading: These newly found genes can help us live even longer but long life hides a risk you should know