Could a Drug Give Your Pet More Dog Years?
By Emily Anthes, Nov. 28, 2023, NY Times
The life of a pet dog follows a predictable trajectory. Over time, the floppy-eared puppy that keeps falling asleep in his food bowl will become a lanky-legged adolescent with an insatiable interest in squirrels — before eventually settling into
adulthood as a canine creature of habit, with a carefully chosen napping location and a well-rehearsed greeting ritual.

But as the years progress, his joints will stiffen and his muzzle will gray. And one day, which will inevitably arrive too soon, his wagging tail will finally still.

“When you adopt a dog, you’re adopting future heartbreak,” said Emilie Adams, a New Yorker who owns three Rhodesian Ridgebacks. “It’s worth it over time because you just have so much love between now and when they go. But their life spans are
shorter than ours.”

In recent years, scientists have been chasing after drugs that might stave off this heartbreak by extending the lives of our canine companions. On Tuesday, the biotech company Loyal announced that it had moved one step closer to bringing one such drug to
market. “The data you provided are sufficient to show that there is a reasonable expectation of effectiveness,” an official at the U.S. Food and Drug Administration informed the company in a recent letter. (Loyal provided a copy of the letter to The
Times.)

That means that the drug, which Loyal declined to identify for proprietary reasons, has met one of the requirements for “expanded conditional approval,” a fast-tracked authorization for animal drugs that fulfill unmet health needs and require
difficult clinical trials. The drug is not available to pet owners yet, and the F.D.A. must still review the company’s safety and manufacturing data. But conditional approval, which Loyal hopes to receive in 2026, would allow the company to begin
marketing the drug for canine life extension, even before a large clinical trial is complete.

“We’re going to be going for claiming at least one year of healthy life span extension,” said Celine Halioua, the founder and chief executive of Loyal.

Whether the drug will actually deliver on that promise is unknown. Although a small study suggests LOY-001 might blunt metabolic changes associated with aging, Loyal has not yet demonstrated that it lengthens dogs’ lives.

But the letter, which came after years of discussion between Loyal and the F.D.A., suggests that the agency is open to canine longevity drugs, Ms. Halioua said.

More are in the pipeline. A team of academic researchers is currently conducting a canine clinical trial of rapamycin, which has been shown to extend the lives of lab mice. And Loyal is recruiting dogs for a clinical trial of another drug candidate,
dubbed LOY-002.

These developments are a sign of the accelerating pace of the science and the seriousness with which researchers and regulators are taking a field that once seemed like science fiction. They also raise questions about what it might mean to succeed, said
Daniel Promislow, a biogerontologist at the University of Washington and a co-director of the Dog Aging Project, which is conducting the rapamycin trial.

“What if it works?” he said. “What are the implications?”

Lapping at the fountain of youth
-----------------------------------
Aging may be an inevitability, but it is not an unyielding one. Scientists have created longer-lived worms, flies and mice by tweaking key aging-related genes.

These findings have raised the tantalizing possibility that scientists might be able to find drugs that had the same life-extending effects in people. That remains an active area of research, but canine longevity has recently started to attract more
attention, in part because dogs are good models for human aging and in part because many pet owners would love more time with their furry family members.

“There’s not a lot you wouldn’t do if you could stack the deck in your favor to preserve the life of your hairy, four-legged child,” said Ms. Adams, the Rhodesian Ridgeback owner.

The drugs currently under investigation act in different ways. Rapamycin, which has also attracted intense interest as a potential longevity drug for humans, inhibits a protein known as mTOR, which regulates cell growth and metabolism.

Earlier this year, a team of scientists including Dr. Promislow and some of his colleagues at the Dog Aging Project published an analysis of dogs that had been randomly assigned to receive either a low dose of rapamycin or a placebo for six months.
Although the sample size was small, 27% of dog owners whose pets received the drug reported improvements in health or behavior, including increases in activity or playfulness, compared with 8% of owners whose dogs received a placebo.

LOY-001, an extended-release implant intended for large, adult dogs, is designed to modulate a different growth-related compound: insulinlike growth factor-1, or IGF-1. The IGF-1 pathway has been associated with aging and longevity in several species; in
dogs, it is known to play a key role in determining body size. Although the idea remains unproven, some scientists hypothesize that high IGF-1 levels drive both rapid growth and accelerated aging in large dogs, which generally have shorter life spans
than small ones.

Loyal’s own research, which has not yet been published, suggests that LOY-001 does reduce IGF-1 levels in dogs and that it might curb aging-related increases in insulin; an observational study of nearly 500 dogs also suggested that lower insulin levels
were correlated with reduced frailty and a higher quality of life.

“It’s quite an exciting approach,” said Colin Selman, a biogerontologist of aging at the University of Glasgow, who was not involved in the research and had not personally reviewed the company’s data.

But proving that a drug can actually extend canine lives will require large, time-consuming clinical trials. Although some are currently underway, it will be at least several more years before the results are in. And regardless of the drug, researchers
will need to demonstrate that it adds good, healthy years to a dog’s life, rather than just drawing out their decline, experts said.

“If it proves true that it extends life span, I’m only interested in that if the period of life that is extended is good quality life,” said Dr. Kate Creevy, a veterinarian at Texas A&M and the chief veterinary officer of the Dog Aging Project. “
I don’t want to make my dog live an extra two years in poor health.”

Canine conundrums
-------------------
It is too soon to say what longevity drugs will cost, but Ms. Halioua predicted that LOY-001 would work out to “mid-double-digit dollars per month.”

For some owners, cost will not be a deterrent, said Karen Cornelius of Illinois, who has owned mastiffs and other “giant” breeds for decades. Many died when they were about 9 years old, said Ms. Cornelius, who runs several Facebook groups for owners
of giant dogs.

“We were just having a discussion on one of my forums yesterday about how short-lived they were, and how people would give almost anything if they could extend that life,” she said.

Some ethicists worried that this enthusiasm could be exploited, especially if the drugs are advertised as fountains of canine youth while questions of long-term safety and efficacy remain unresolved. The dogs themselves cannot give consent, they noted.

“Is it in their best interest to live a little bit longer when there’s some risk to taking these drugs?” said Rebecca Walker, a philosopher and bioethicist at the University of North Carolina at Chapel Hill, who said she would not give a longevity
drug to her golden retriever. “Or is it really in the best interest of their owners, who are very attached to them?”

So far, the worst side effect of LOY-001 has been mild and temporary gastrointestinal distress, Ms. Halioua said, although she acknowledged that the bar for safety would be “extremely, extremely, extremely high.”

Longevity drugs are intended for healthy dogs, which changes the risk-benefit calculus. “It’s one thing if a dog is on death’s door and you’re giving them some late-breaking treatment,” said Bev Klingensmith, a Great Dane breeder in Iowa who
also has a Great Dane and a golden retriever of her own. “Giving my young, healthy dog a brand-new drug would seem a little scary.”

Even drugs that deliver on all their promises will raise ethical questions. “If animals are living longer, do we have the resources and commitment to provide lives worth living?” Dr. Anne Quain, a veterinarian and an expert on veterinary ethics at
the University of Sydney, said in an email. “What if we see more dogs outliving their owners?”

Reforming the breeding practices that have contributed to life-shortening health problems in many dogs and expanding access to basic veterinary care might be a better way to improve canine lives, she added. “We can save many ‘dog years’ by ensuring
that as many dogs have access to that care as possible,” she said.

And while scientists gather more data on potential longevity drugs, there are steps that dog owners can now take to foster healthier aging, experts said, including keeping their dogs lean and providing ample exercise and mental stimulation.

Ms. Halioua admitted to having a soft spot for senior dogs. “They just want a nice bed to sleep on,” she said, as her elderly Rottweiler, Della, napped. Della, who has lymphoma and dementia, is not on LOY-001 because enrolling her in the company’s
studies would present a conflict of interest, Ms. Halioua said, but the dog seemed happy, she noted.

Ultimately, even if scientists can delay a pet owner’s heartbreak, they are unlikely to prevent it altogether. “These are definitely not immortality or radical life-span-extension drugs,” Ms. Halioua said in an email. She added, “Nothing we are
developing could make a dog live forever.”

https://www.nytimes.com/2023/11/28/science/longevity-drugs-dogs.html

https://www.med.unc.edu/socialmed/directory/rebecca-walker/

=============

A Giant Inland Sea Is Now a Desert, and a Warning for Humanity
By Jacob Dreyer, Nov. 28, 2023, NY Times
Walking toward the shrinking remnants of what used to be the Aral Sea in Uzbekistan was like entering hell.

All around was a desert devoid of life, aside from scrubby saxaul trees. Dust swirled in 110-degree Fahrenheit heat under a throbbing red sun. I reached the edge of one of the scattered lakes that are all that remain of this once-great body of water. I
took off my shoes and waded in. The water was so full of salt that it felt viscous, not quite liquid.

In the nearby town of Muynak, black-and-white newsreels in the local museum and pictures in the family photo albums of residents tell of better times. During the Soviet era, fishing communities like Muynak ringed the sea, thriving off its bounty:
sturgeon, flounder, caviar and other staples of Soviet dinner tables. In the town I met Oktyabr Dospanov, an archaeologist who grew up along the Aral’s shores and recalls a “happy life” in his youth, when fishing boats, passenger ships and cargo
trawlers plied the sea’s waves around the clock.

But over the decades, Soviet authorities diverted rivers that flowed into the sea to irrigate cotton and other crops. The world’s fourth-largest inland body of water — which covered an area about 15% larger than Lake Michigan — gradually shrank,
triggering a domino effect of ecological, economic and community collapse, the kind of catastrophe that could befall other environmentally fragile parts of the world unless we change our ways.

By 2007, the sea’s surface area had shrunk by around 90%, leaving Muynak a landlocked way station for tourists who come to marvel at this ecological disaster, where they take selfies near rusting ship hulks that are perched high and dry in the endless
sand.

Although restoration efforts in recent years have led to small improvements in some areas, the former expanse of the Aral Sea is a blighted realm, where a scattering of far smaller, brackish lakes lie like puddles in a vast dry basin. The Aral Sea is now
the Aralkum Desert. Over the decades, soil and water were contaminated by pesticides and other pollutants, which are suspected of causing birth defects and other chronic health problems in the area.

As the Aral Sea died, the region’s once-rich pastures and forests began to degrade, according to Mr. Dospanov. Birds, insects and other wildlife that depend on the sea and its wider environment disappeared. It was as if without the sea, biodiversity
went into freefall.

Salty dust blown from the parched seabed has severely affected crops. Other livelihoods tied to the sea have also suffered, and over the decades local incomes fell and unemployment rose. The population of the region dropped as people migrated to the
Uzbek capital, Tashkent, or to Moscow, where many work in construction or other low-paying jobs and often face discrimination. An entire natural and human ecosystem was destroyed. Worse, the Soviet authorities knew what was happening, but priorities like
economic growth seemed more important. By the 1980s, authorities even considered compounding the folly by diverting water from Lake Baikal in Siberia, more than 2,000 miles away, to the Aral region. The Soviet Union collapsed before that scheme could be
carried out.

Last year, protests broke out in Karakalpakstan, the region where the Aral Sea was, after a proposal by the government of Uzbekistan that would have reduced the region’s autonomy. Many observers have noted that economic and environmental hardship
related to the sea’s demise have added to the region’s volatility.

The really scary thing about the Aral Sea is that environmental catastrophes like it are being replicated across the world. We see refugees fleeing from uninhabitable homelands, bitter conflicts over scarce resources and land, and cities threatened by
rising sea levels.

In the United States, Lake Mead and the Great Salt Lake are shrinking, and cities like Los Angeles are racing to balance their water needs with a changing climate. Agriculture, fracking, lawn maintenance and other activities are rapidly depleting
groundwater aquifers across America. Can we live with the possibility that other places are headed for a fate similar to the Aral Sea’s? The human race is using up its water and other resources like there’s no tomorrow, but as the residents of Muynak
found out, there was a tomorrow, just not the one they were hoping for.

For Mr. Dospanov, the sea was a microcosm of humanity’s deep economic and social connection to the environment. A culture and a way of life blossomed around the Aral Sea, in symbiosis with it, dependent upon it. But the sea’s destruction caused
everything else to collapse along with it, he said.

I left for Tashkent to catch a flight back to China, where I live, eager to leave Karakalpakstan behind. But I would have to wait: Beijing had been hit by the heaviest rains in years (prompting discussion of whether climate change was partly to blame),
stranding me for a while in Tashkent.

The Aral Sea stands as a grim parable, a warning of what can come from humanity’s environmental hubris. If we continue this way, waiting for somebody else to do something or letting short-term economic interests stand in the way, we may find ourselves
like Mr. Dospanov, telling visitors about how beautiful our home once was

https://www.nytimes.com/2023/11/28/opinion/climate-uzbekistan-water-aral.html

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