How African turquoise killifish press the pause button on aging


When the ponds where one
African fish lives dry up, its offspring put their lives on pause. And now
researchers have a sense for how the creatures do it.  

African turquoise killifish embryos
can halt their development during
a state of suspended activity called diapause. Now a study shows that the embryos
effectively don’t age while in that state. Genetic analyses reveal that, to
stay frozen in time, the embryos put functions
such as cell growth and organ development on hold, researchers report in the Feb. 21 Science.

“Nature has identified ways
to pause the clock,” says Anne Brunet, a geneticist Stanford University.
Knowing how killifish pause their lives could help scientists figure out how to
treat aging-related diseases or learn how to preserve human organs long-term,
she says.

Nematode worm larvae (Caenorhabditis elegans) can also halt
development and aging when faced with a lack of food or if their environment is
overcrowded. Invertebrates
like nematodes, however, lack many of the features that make other animals age,
such as an adaptive immune system. More
than 130 species of mammals from mice to bears also have some form of diapause.

The killifish (Nothobranchius furzeri) live in ponds in Mozambique and Zimbabwe that disappear for months during the dry season, leaving the fish without a home until the rain returns (SN: 8/6/18). For adults that typically live only four to six months anyway, vanishing ponds don’t pose much of a threat. But some killifish embryos press pause on their development during dry months, until ponds fill up again. 

Killifish advance from colorful, young fish to pale, old fish within a few months, making them a good animal for scientists to use to study aging.Chi-Kuo Hu

embryos can put their growth on hold from five months up to two years, matching
or even greatly exceeding their typical adult life span. If humans could do
something similar, an 80-year-old person might instead have a life span from 160
to more than 400 years, Brunet says. But if, or how, these animals protect
themselves from aging while in this limbo was unknown.

In the study, Brunet and her
colleagues compared killifish embryos that halted their growth with those that
bypassed diapause and hatched into adults. Diapause didn’t decrease an adult
fish’s growth, life span or ability to reproduce — a sign that the animal didn’t age, even if it paused its
development for longer than its typical lifetime, the researchers found.

The team
then analyzed the genetic blueprint of embryos suspended in diapause to
determine which genes were active. Although the young killifish had developing
muscles, hearts and brains before diapause, genes involved in organ development
and cell proliferation were subsequently turned off. But other genes were
cranked up, such as some crucial for turning other sets of genes on or off.

Killifish embryos (one pictured) can pause their development for a few months or up to two years during a state of suspended activity called diapause.Chi-Kuo Hu

One gene,
the chromobox 7 gene, or CBX7,
repressed genes involved in metabolism, but turned on those important for
maintaining muscle and staying in diapause, the researchers found. Embryos
without CBX7 came out of diapause
sooner, and their muscles began to deteriorate after one month.

The new
study shows that the embryos aren’t passively waiting for better environmental
conditions — their cells coordinate responses during diapause that protect
killifish from the passage of time. “We have
always looked at this diapause state as more passive — nothing happens there,” says Christoph Englert, a molecular geneticist
at the Leibniz Institute on Aging in Jena, Germany, who wasn’t involved in the
work. But the new research “shifts the paradigm of diapause as a passive,
boring state to an active state of embryonic nondevelopment.”

Researchers aren’t sure how things
like temperature might spark a developing killifish to begin or end diapause. But
understanding what’s going on inside an embryo is a step toward pinpointing how
external signals might control when the animals suspend time, Englert

The earliest known hominid interbreeding occurred 700,000 years ago


Ancestors of Neandertals and Denisovans left Africa for
Eurasia around 700,000 years ago and then interbred with a Homo population that had exited
Africa long before, according to a new genetic study. The finding reveals the
oldest known case of interbreeding among members of the genus that includes
people today, Homo sapiens.

Evidence of genetic exchanges between distinct hominid populations
roughly 400,000 years before H. sapiens
evolved highlights a role for interbreeding in Homo evolution long before ancient people occasionally mated with
Neandertals and Denisovans.  

The scenario begins with an early Homo species making its way into Eurasia roughly 1.9 million years
ago, in what was probably the first Homo
migration out of Africa, scientists report February 20 in Science Advances. Those now-extinct travelers may have been members
of Homo erectus, a species that
includes Eurasian fossils dating to about 1.8 million years ago (SN: 10/17/13), or Homo antecessor, a controversial
species designation based on 1.2-million- to 1.1-million-year-old fossils found
in Spain (SN: 3/26/08). Or they could
have been part of another Homo population
unknown from any fossils.

Then ancestors of Neandertals and Denisovans trekked out of
Africa about 700,000 years ago, say the researchers, led by anthropologist and
population geneticist Alan Rogers of the University of Utah in Salt Lake City. That
timing would also have allowed for the evolution of Neandertals
or their direct ancestors in what’s now northern Spain
around 430,000 years
ago (SN: 3/14/16). Some previous
research had suggested that Neandertals originated roughly 300,000 years ago,
raising questions about the evolutionary identity of older, Neandertal-like
fossils in Spain.

Rogers refers to ancestors of Neandertals and Denisovans as “neandersovans.”
That genetically distinct population existed for a brief period of perhaps
15,000 years, Rogers estimates. Neandersovans’ numbers declined sharply after they
left Africa around 700,000 years ago, he suspects. Survivors interbred with members
of the Homo population that had long
inhabited Eurasia, before largely replacing them and separating into eastern
and western populations — Denisovans and Neandertals, respectively. Neandersovans
inherited at least 2 percent of their DNA from the older Eurasian Homo population, Rogers calculates.

“It’s interesting that signals of interbreeding that far
back can be seen in our genomes,” says UCLA geneticist Sriram Sankararaman.
Further research needs to look for genetic links between members of that
probable first Homo departure from
Africa, identified in Rogers’ study, and a
previously unknown Homo population

that lived 1 million years ago or more and left a genetic mark on present-day
West Africans, Sankararaman suggests (SN:
). A genetic analysis by the UCLA researcher’s team identified the
latter Homo group.

The new findings rest on a novel analysis of particular sets
of gene variants found in people today, as well as in Neandertal and Denisovan
fossils. Rogers previously determined that these gene forms had not undergone
recent changes and thus could be traced back to ancient populations. A software
program compared frequencies of the gene variants in DNA from three modern West
African Yorubans, five French individuals, two English people, a Neandertal from
Croatia’s Vindija Cave, a Neandertal from Siberia’s Denisova Cave and a
Denisovan from the same Siberian site.

The researchers identified the best of eight simulations of
how ancient interbreeding could have produced the shared genetic variants
observed in both the modern and ancient individuals. Estimates of the rate at
which genetic mutations accumulate enabled the scientists to gauge the timing
of the ancient African departures.

While the newly proposed timing of interbreeding around
700,000 years ago seems reasonable, Rogers’ genetic data deserve closer
scrutiny with alternative statistical techniques, says zoologist and
evolutionary geneticist Peter Waddell of the Ronin Institute, a nonprofit
research center in Montclair, N.J. Waddell previously found signs of a small
amount of ancestry
in Denisovan DNA from a much older Homo
, possibly H. erectus.

Rogers and his colleagues also suggest that a third major
expansion out of Africa, involving H.
, occurred around 50,000 years ago. As with the neandersovan
expansion, the genetic evidence is consistent with H. sapiens arriving in Eurasia and then interbreeding with resident
Neandertals and Denisovans before replacing those populations, the scientists
say. Other fossil and ancient DNA studies, though, indicate that some
H. sapiens reached Southeast Asian
more than 60,000 years ago (SN:

Economic costs of rising seas will be steeper than we thought, unless we prepare


Rising seas that swamp cities and coastal infrastructure could cost the world more than 4 percent of the global economy each year by 2100 — far more than previously estimated — unless urgent action is taken both to reduce greenhouse gas emissions and to prepare for such impacts from climate change, a new study finds. 

That worst-case scenario, which assumes that large amounts of polar ice will melt, could come to trillions of dollars. That’s “not peanuts,” says Thomas Schinko, a climate economist and deputy director of the Risk and Resilience program at the International Institute for Applied Systems Analysis in Vienna. “This would lead to a completely different world.” 

Given the risks, it’s hard to imagine that people won’t make any effort to adapt to a world with more flooding and coastal erosion, Schinko says. So that worst-case scenario is “not a very realistic scenario.” But regardless if the 4 percent global loss actually materializes, he says, the shocking number should show policy makers what could happen if they don’t act soon.

If countries lower greenhouse gas emissions enough to prevent the global temperature from rising more than 2 degrees Celsius above preindustrial levels, but do nothing else to prepare for rising seas, costs are projected to be more than 3 percent of global gross domestic product each year by 2100, the report says. But if countries lower emissions and prepare for sea level rise, costs can be limited to about 0.4 percent of global GDP or less, Schinko and his colleagues found. 

The study, published January 14 in Environmental Research Communications, goes beyond previous studies that estimated about 1.3 percent of global GDP in losses from seas rising on average by up to a meter (SN: 8/15/18). But where previous studies relied on one type of economic model, the new study uses three different types of macroeconomic models to test how different energy policies and emissions scenarios might play out on the global economy — as well as in specific countries — over the next eight decades. 

The researchers also considered how those economic impacts might change if coastal communities prepare for the increased risk of inundation, for example, by building dikes or sea walls (SN: 8/6/19). Previous studies had not taken all of these factors into account simultaneously. The team’s computer simulations adjusted as time went on, including local sea level rise changes and impacts from earlier years in estimating costs for later years. And the team looked at the economic effects of direct losses such as destroyed infrastructure, as well as indirect costs that can ripple through the economy, such as job losses and disrupted supply chains that can result from damage to businesses. 

Those models show that, regardless of the emissions scenario, global GDP losses will probably be relatively low overall through 2050, amounting to less than 0.4 percent annually, on average. But then, costs start to escalate — more or less depending on how much the world does to rein in climate-warming emissions and prepare for rising seas. 

The bottom line is, Schinko says, is that if we don’t do anything now, the costs and the effects of rising seas will skyrocket over the latter half of this century. “If we embark on the wrong trajectory, the impacts will be substantial.”

What’s more, “in this study, we’re only talking about the economic impacts of coastal flooding due to sea level rise, not droughts or wildfires … not salinity intrusion or loss of land” or other hazards like severe storms, Schinko says. Damages from climate change overall could be significantly worse. 

Losses from sea level rise would be spread unevenly across the world. China, for example, could lose up to 12 percent of its GDP each year by 2100; for China’s 2019 GDP, that amounts to $1.7 trillion. Losses in Japan could hit 8 percent annually; Europe, up to 6 percent annually, according to the report. 

The researchers note that their study still falls short of estimating the true cost of rising seas. For example, flooding from hurricanes and typhoons isn’t well represented, says study coauthor Daniel Lincke, a computer scientist and researcher at the Global Climate Forum in Berlin. 

Also not well-represented yet are compound floods — flooding made worse by additional high tides or heavy rainfall — which are probably the biggest problem arising from sea level rise, says coastal engineer Robert Nicholls, director of the Tyndall Centre for Climate Change Research at the University of East Anglia in Norwich, England. 

And of course, sea level rise projections themselves are a moving target. Projections based on ice melt, depending on how much greenhouse gases the world emits, vary from 25 centimeters to close to a meter by 2100. But that could change, as climate change simulations become increasingly sophisticated in incorporating more expected impacts from warmer atmospheric temperatures (SN: 1/7/20). 

Data that go into all of these models are getting better all the time, Lincke says. In just the last few months, researchers have tripled the number of people now living in areas likely to be inundated by floods over the next century, based on better elevation data (SN: 10/29/19). Studies have also revised value estimates for infrastructure and assets in floodplains around the world, revised population maps and examined changes in ocean circulation patterns that could make a big difference in sea level projections. 

The economic models used in the newest study took these revisions into account, as well as data about what’s actually happening now in coastal communities, Lincke says. Some coastal communities are doing nothing, while others are taking action to deal with climate-related flooding, for example, by building sea walls or moving expensive infrastructure (SN: 8/6/19). 

This preparation is key, researchers say. The world already is “beginning to see impacts — things like nuisance flooding along the East Coast of the U.S.,” Nicholls says. Even if countries manage to drastically curb their carbon emissions at this point, “seas will continue to rise. You can’t just turn off the tap. We have to prepare.”

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U.S. drug deaths dipped in 2018, but cocaine and meth overdoses rose


The stories that Judith
Feinberg hears from people with substance use disorder are riddled with loss:
of jobs, opportunity, security, dignity. “People really are struggling to see
that they have a viable future,” Feinberg says. “Then you take a drug … and you
don’t care until you need the drug again.”

For years, that drug was very
likely an opioid. But Feinberg, a physician at West Virginia University School
of Medicine in Morgantown who studies infectious diseases and injection drug
use, recently has seen shifts in the addictive substances used. And it’s
occurring not just in West Virginia — which has the highest rate of drug overdose deaths in
the nation, at 51.5 deaths per 100,000 people — but across the country, the U.S. Centers for Disease
Control and Prevention reported January 30.

Fueled by a plentiful
supply, people have increasingly been turning to such stimulants as cocaine and
methamphetamine — so much so that the rates of overdose deaths for those drugs each
surpassed that of prescription opioids in 2018.

There’s a small bit of hope:
After two decades of rising numbers, around 3,000 fewer people overall died of a drug overdose in 2018 than in 2017. But with 67,367 deaths, 2018 ranks
as the second-worst year for drug overdoses in U.S. history. It’s too soon to
say whether the nudge downward is a blip or the start of a meaningful drop.

In part, that may depend
upon whether the rise in stimulant use over much of the last decade continues. In
2018, the rate of overdose deaths involving cocaine was 4.5 per 100,000, more
than triple what it was in 2012; for methamphetamine and similar drugs, the
rate jumped from 0.8 to 3.9 per 100,000 during that period. Each now surpasses
the death rate from prescription opioids, and cocaine’s rate is just shy of

While the rates of overdose
deaths for prescription opioids and heroin each fell from 2017 to 2018,
suggesting some success in national efforts to address the opioid epidemic, deaths
from fentanyl and other synthetic opioids (SN: 5/1/18) continue to go
up, hitting 9.9 per 100,000 in 2018.

Opioids are depressants that
slow the body down and can halt breathing (SN: 3/29/18).
In contrast, stimulants like methamphetamine and cocaine ramp up the body,
increasing blood pressure, heart rate and body temperature. The drugs can also
make a person hallucinate or feel anxious or paranoid. An overdose can lead to
a fatal heart attack or stroke.

Although the outward effects
on a person’s body are different, stimulants and depressants both produce a
feeling of euphoria in the user. The drugs also lead to the release of dopamine,
a brain chemical that encourages a person to repeat pleasurable activities. “It’s
that dopamine release that is the hallmark of addiction,” Feinberg says.

Which drugs rise to the
forefront of the nation’s ongoing addiction crisis can change depending on
availability and cost. “We know that drug use comes in cycles,” says Jane
Maxwell, an epidemiologist at the University of Texas at Austin who tracks
trends in drug use. That cyclic nature, she says, partly depends upon what’s
easy to get.

Cocaine, for example, is
making a comeback, after being a major drug of abuse in the ’70s and ’80s. Colombia
is the primary source of cocaine in the United States. Since the country signed
a peace treaty with guerrilla fighters in 2016, coca plant cultivation and
cocaine production have risen, Maxwell says. That has increased the supply and
decreased the cost of the drug in the United States.

There’s also a large supply
of methamphetamine in the United States, but what’s widely available today is
more potent — with more potential for abuse — than in the past. The stimulant
used to be made from pseudoephedrine or ephedrine, ingredients in cold
medicines, but the United States limited over-the-counter sales of those drugs
in 2006. Today, meth is largely produced in Mexico in what’s known as the “P2P”
production method (Walter White turned to this method in later seasons of the
television series Breaking Bad). That
process creates a chemical form of meth that “has much more of a euphoric
effect,” Maxwell says.

Right now, the public health
toolkit against stimulant addiction lacks any pharmaceutical help, which
severely hampers the response. To counter the opioid epidemic, medications are
available, including buprenorphine to treat dependence on opioids and naloxone
to reverse an overdose. But no drugs have been approved to manage addiction to stimulants.

With the drugs that lead to
substance use disorders shifting over time, “all of this stuff is a moving
target,” Feinberg says. Focusing efforts on a particular drug doesn’t address
the larger societal problems that underlie substance use, she argues. “The real
question in my mind is, why do so many people in this country need to find
oblivion in some chemical experience?”

Media Invited to Inside Look at NASA Marine Cloud Study

Media are invited to preview a NASA airborne science campaign to help improve weather and climate predictions at 9 a.m. EST Tuesday, Feb. 25, at NASA’s Langley Research Center in Hampton, Virginia.