Drugs That Could Slow Aging May Hold Promise for Protecting the Elderly from COVID-19
Although recent data has shown the coronavirus poses a greater risk to young people than previously understood, the ensuing COVID-19 disease is clearly far more dangerous for older people than it is for the young.
If we want to lower the COVID-19 fatality rate, we must also make fortifying our most vulnerable hosts a central part of our approach.
While our older adults have accrued tremendous knowledge, wisdom, and perspective over the years, their bodies have over time become less able to fight off viruses and other insults. The shorthand name for this increased susceptibility is aging.
We may have different names for the diseases which disproportionately kill us -- cancer, heart disease, and dementia among them – but what is really killing us is age. The older we are, the greater the chance we'll die from one or another of these afflictions. Eliminate any one completely - including cancer - and we won't on average live that much longer. But if we slow aging on a cellular level, we can counter all of these diseases at once, including COVID-19.
Every army needs both offensive and defensive capabilities. In our war against COVID-19, our offense strategy is to fight the virus directly. But strengthening our defense requires making us all more resistant to its danger. That's why everyone needs to be eating well, exercising, and remaining socially connected. But if we want to lower the COVID-19 fatality rate, we must also make fortifying our most vulnerable hosts a central part of our approach. That's where our new fight against this disease and the emerging science of aging intersect.
Once the domain of charlatans and delusionists, the millennia-old fantasy of extending our healthy lifespans has over the past century become real. But while the big jump in longevity around the world over the past hundred years or so is mostly attributable to advances in sanitation, nutrition, basic healthcare, and worker safety, advances over the next hundred will come from our increasing ability to hack the biology of aging itself.
A few decades ago, scientists began recognizing that some laboratory animals on calorie-restricted diets tended to live healthier, longer lives. Through careful experiments derived from these types of insights, scientists began identifying specific genetic, epigenetic, and metabolic pathways that influence how we age. A range of studies have recently suggested that systemic knobs might metaphorically be turned to slow the cellular aging process, making us better able to fight off diseases and viral attacks.
Among the most promising of these systemic interventions is a drug called metformin, which targets many of the hallmarks of aging and extends health span and lifespan in animals. Metformin has been around since the Middle Ages and has been used in Europe for over 60 years to treat diabetes. This five-cent pill became the most prescribed drug in the world after being approved by the FDA in 1994.
With so many people taking it, ever larger studies began suggesting metformin's positive potential effects preventing diabetes, cardiovascular diseases, cancer, and dementia. In fact, elderly people on metformin for their diabetes have around a 20 percent lower mortality than age-matched subjects without diabetes. Results like these led scientists to hypothesize that metformin wasn't just impacting a few individual diseases but instead having a systemic impact on entire organisms.
Another class of drug that seems to slow the systemic process of aging in animal models and very preliminary human trials inhibits a nutrient-sensing cellular protein called mTOR. A new category of drugs called rapalogues has been shown to extend healthspan and lifespan in every type of non-human animal so far tested. Two recent human studies indicated that rapalogues increased resistance to the flu and decreased the severity of respiratory tract infections in older adults.
If COVID-19 is primarily a severe disease of aging, then countering aging should logically go a long way in countering the disease.
These promising early indications have inspired a recently launched long-term study exploring how metformin and rapalogues might delay the onset of multiple, age-related diseases and slow the biological process of aging in humans. Under normal circumstances, studies like this seeking to crack the biological code of aging would continue to proceed slowly and carefully over years, moving from animal experiments to cautious series of human trials. But with deaths rising by the day, particularly of older people, these are not times for half measures. Wartimes have always demanded new ways of doing important things at warp speeds.
If COVID-19 is primarily a severe disease of aging, then countering aging should logically go a long way in countering the disease. We need to find out. Fast.
Although it would be a mistake for older people to just begin taking drugs like these without any indication, pushing to massively speed up our process for assessing whether these types of interventions can help protect older people is suddenly critical.
To do this, we need U.S. government agencies like the Department of Health and Human Services' Biomedical Advanced Research and Development Authority (BARDA) to step up. BARDA currently only funds COVID-19 clinical trials of drugs that can be dosed once and provide 60 days of protection. Metformin and rapalogues are not considered for BARDA funding because they are dosed once daily. This makes no sense because a drug that provides 60 days of protection from the coronavirus after a single dose does not yet exist, while metformin and rapalogues have already passed extensive safety tests. Instead, BARDA should consider speeding up trials with currently available drugs that could help at least some of the elderly populations at risk.
Although the U.S. Food and Drug Administration and Centers for Disease Control are ramping up their approval processes and even then needs to prioritize efforts, they too must find a better balance between appropriate regulatory caution and the dire necessities of our current moment. Drugs like metformin and rapalogues that have shown preliminary efficacy ought to be fast-tracked for careful consideration.
One day we will develop a COVID-19 vaccine to help everyone. But that could be at least a year from now, if not more. Until we get there and even after we do, speeding up our process of fortifying our older populations mush be a central component of our wartime strategy.
And when the war is won and life goes back to a more normal state, we'll get the added side benefit of a few more months and ultimately years with our parents and grandparents.
Breakthrough drones deliver breast milk in rural Uruguay
Until three months ago, nurse Leopoldina Castelli used to send bottles of breast milk to nourish babies in the remote areas of Tacuarembó, in northern Uruguay, by way of ambulances or military trucks. That is, if the vehicles were available and the roads were passable, which wasn’t always the case. Now, five days per week, she stands by a runway at the hospital, located in Tacuarembó’s capital, watching a drone take off and disappear from view, carrying the milk to clinics that serve the babies’ families.
The drones can fly as far as 62 miles. Long distances and rough roads are no obstacles. The babies, whose mothers struggle to produce sufficient milk and cannot afford formula, now receive ample supplies for healthy growth. “Today we provided nourishment to a significantly larger number of children, and this is something that deeply moves me,” Castelli says.
About two decades ago, the Tacuarembó hospital established its own milk bank, supported by donations from mothers across Tacuarembó. Over the years, the bank has provided milk to infants immediately after birth. It's helped drive a “significant and sustained” decrease in infant mortality, says the hospital director, Ciro Ferreira.
But these children need breast milk throughout their first six months, if not longer, to prevent malnutrition and other illnesses that are prevalent in rural Tacuarembó. Ground transport isn't quick or reliable enough to meet this goal. It can take several hours, during which the milk may spoil due to a lack of refrigeration.
The battery-powered drones have been the difference-maker. The project to develop them, financed by the UNICEF Innovation Fund, is the first of its kind in Latin America. To Castelli, it's nothing short of a revolution. Tacuarembó Hospital, along with three rural clinics in the most impoverished part of Uruguay, are its leaders.
"This marks the first occasion when the public health system has been directly impacted [by our technology]," says Sebastián Macías, the CEO and co-founder of Cielum, an engineer at the University Republic, which collaborated on the technology with a Uruguayan company called Cielum and a Swiss company, Rigitech.
The drone can achieve a top speed of up to 68 miles per hour, is capable of flying in light rain, and can withstand winds of up to 30 miles per hour at a maximum altitude of 120 meters.
"We have succeeded in embracing the mothers from rural areas who were previously slipping through the cracks of the system," says Ferreira, the hospital director. He envisions an expansion of the service so it can improve health for children in other rural areas.
Nurses load the drone for breast milk delivery.
Sebastián Macías - Cielum
The star aircraft
The drone, which costs approximately $70,000, was specifically designed for the transportation of biological materials. Constructed from carbon fiber, it's three meters wide, two meters long and weighs 42 pounds when fully loaded. Additionally, it is equipped with a ballistic parachute to ensure a safe descent in case the technology fails in midair. Furthermore, it can achieve a top speed of 68 miles per hour, fly in light rain, and withstand winds of 30 miles per hour at a height of 120 meters.
Inside, the drones feature three refrigerated compartments that maintain a stable temperature and adhere to the United Nations’ standards for transporting perishable products. These compartments accommodate four gallons or 6.5 pounds of cargo. According to Macías, that's more than sufficient to carry a week’s worth of milk for one infant on just two flights, or 3.3 pounds of blood samples collected in a rural clinic.
“From an energy perspective, it serves as an efficient mode of transportation and helps reduce the carbon emissions associated with using an ambulance,” said Macías. Plus, the ambulance can remain available in the town.
Macías, who has led software development for the drone, and three other technicians have been trained to operate it. They ensure that the drone stays on course, monitor weather conditions and implement emergency changes when needed. The software displays the in-flight positions of the drones in relation to other aircraft. All agricultural planes in the region receive notification about the drone's flight path, departure and arrival times, and current location.
The future: doubling the drone's reach
Forty-five days after its inaugural flight, the drone is now making five flights per week. It serves two routes: 34 miles to Curtina and 31 miles to Tambores. The drone reaches Curtina in 50 minutes while ambulances take double that time, partly due to the subpar road conditions. Pueblo Ansina, located 40 miles from the state capital, will soon be introduced as the third destination.
Overall, the drone’s schedule is expected to become much busier, with plans to accomplish 20 weekly flights by the end of October and over 30 in 2024. Given the drone’s speed, Macías is contemplating using it to transport cancer medications as well.
“When it comes to using drones to save lives, for us, the sky is not the limit," says Ciro Ferreira, Tacuarembó hospital director.
In future trips to clinics in San Gregorio de Polanco and Caraguatá, the drone will be pushed to the limit. At these locations, a battery change will be necessary, but it's worth it. The route will cover up to 10 rural Tacuarembó clinics plus one hospital outside Tacuarembó, in Rivera, close to the border with Brazil. Currently, because of a shortage of ambulances, the delivery of pasteurized breast milk to Rivera only occurs every 15 days.
“The expansion to Rivera will include 100,000 more inhabitants, doubling the healthcare reach,” said Ferreira, the director of the Tacuarembó Hospital. In itself, Ferreira's hospital serves the medical needs of 500,000 people as one of the largest in Uruguay's interior.
Alejandro Del Estal, an aeronautical engineer at Rigitech, traveled from Europe to Tacuarembó to oversee the construction of the vertiports – the defined areas that can support drones’ take-off and landing – and the first flights. He pointed out that once the flight network between hospitals and rural polyclinics is complete in Uruguay, it will rank among the five most extensive drone routes in the world for any activity, including healthcare and commercial uses.
Cielum is already working on the long-term sustainability of the project. The aim is to have more drones operating in other rural regions in the western and northern parts of the country. The company has received inquiries from Argentina and Colombia, but, as Macías pointed out, they are exercising caution when making commitments. Expansion will depend on the development of each country’s regulations for airspace use.
For Ferreira, the advantages in Uruguay are evident: "This approach enables us to bridge the geographical gap, enhance healthcare accessibility, and reduce the time required for diagnosing and treating rural inhabitants, all without the necessity of them traveling to the hospital,” he says. "When it comes to using drones to save lives, for us, the sky is not the limit."
After spaceflight record, NASA looks to protect astronauts on even longer trips
At T-minus six seconds, the main engines of the Atlantis Space Shuttle ignited, rattling its capsule “like a skyscraper in an earthquake,” according to astronaut Tom Jones, describing the 1988 launch. As the rocket lifted off and accelerated to three times the force of Earth's gravity, “It felt as if two of my friends were standing on my chest and wouldn’t get off.” But when Atlantis reached orbit, the main engines cut off, and the astronauts were suddenly weightless.
Since 1961, NASA has sent hundreds of astronauts into space while working to making their voyages safer and smoother. Yet, challenges remain. Weightlessness may look amusing when watched from Earth, but it has myriad effects on cognition, movement and other functions. When missions to space stretch to six months or longer, microgravity can impact astronauts’ health and performance, making it more difficult to operate their spacecraft.
Yesterday, NASA astronaut Frank Rubio returned to Earth after over one year, the longest single spaceflight for a U.S. astronaut. But this is just the start; longer and more complex missions into deep space loom ahead, from returning to the moon in 2025 to eventually sending humans to Mars. To ensure that these missions succeed, NASA is increasing efforts to study the biological effects and prevent harm.
The dangers of microgravity are real
A NASA report published in 2016 details a long list of incidents and near-misses caused – at least partly – by space-induced changes in astronauts’ vision and coordination. These issues make it harder to move with precision and to judge distance and velocity.
According to the report, in 1997, a resupply ship collided with the Mir space station, possibly because a crew member bumped into the commander during the final docking maneuver. This mishap caused significant damage to the space station.
Returns to Earth suffered from problems, too. The same report notes that touchdown speeds during the first 100 space shuttle landings were “outside acceptable limits. The fastest landing on record – 224 knots (258 miles) per hour – was linked to the commander’s momentary spatial disorientation.” Earlier, each of the six Apollo crews that landed on the moon had difficulty recognizing moon landmarks and estimating distances. For example, Apollo 15 landed in an unplanned area, ultimately straddling the rim of a five-foot deep crater on the moon, harming one of its engines.
Spaceflight causes unique stresses on astronauts’ brains and central nervous systems. NASA is working to reduce these harmful effects.
NASA
Space messes up your brain
In space, astronauts face the challenges of microgravity, ionizing radiation, social isolation, high workloads, altered circadian rhythms, monotony, confined living quarters and a high-risk environment. Among these issues, microgravity is one of the most consequential in terms of physiological changes. It changes the brain’s structure and its functioning, which can hurt astronauts’ performance.
The brain shifts upwards within the skull, displacing the cerebrospinal fluid, which reduces the brain’s cushioning. Essentially, the brain becomes crowded inside the skull like a pair of too-tight shoes.
That’s partly because of how being in space alters blood flow. On Earth, gravity pulls our blood and other internal fluids toward our feet, but our circulatory valves ensure that the fluids are evenly distributed throughout the body. In space, there’s not enough gravity to pull the fluids down, and they shift up, says Rachael D. Seidler, a physiologist specializing in spaceflight at the University of Florida and principal investigator on many space-related studies. The head swells and legs appear thinner, causing what astronauts call “puffy face chicken legs.”
“The brain changes at the structural and functional level,” says Steven Jillings, equilibrium and aerospace researcher at the University of Antwerp in Belgium. “The brain shifts upwards within the skull,” displacing the cerebrospinal fluid, which reduces the brain’s cushioning. Essentially, the brain becomes crowded inside the skull like a pair of too-tight shoes. Some of the displaced cerebrospinal fluid goes into cavities within the brain, called ventricles, enlarging them. “The remaining fluids pool near the chest and heart,” explains Jillings. After 12 consecutive months in space, one astronaut had a ventricle that was 25 percent larger than before the mission.
Some changes reverse themselves while others persist for a while. An example of a longer-lasting problem is spaceflight-induced neuro-ocular syndrome, which results in near-sightedness and pressure inside the skull. A study of approximately 300 astronauts shows near-sightedness affects about 60 percent of astronauts after long missions on the International Space Station (ISS) and more than 25 percent after spaceflights of only a few weeks.
Another long-term change could be the decreased ability of cerebrospinal fluid to clear waste products from the brain, Seidler says. That’s because compressing the brain also compresses its waste-removing glymphatic pathways, resulting in inflammation, vulnerability to injuries and worsening its overall health.
The effects of long space missions were best demonstrated on astronaut twins Scott and Mark Kelly. This NASA Twins Study showed multiple, perhaps permanent, changes in Scott after his 340-day mission aboard the ISS, compared to Mark, who remained on Earth. The differences included declines in Scott’s speed, accuracy and cognitive abilities that persisted longer than six months after returning to Earth in March 2016.
By the end of 2020, Scott’s cognitive abilities improved, but structural and physiological changes to his eyes still remained, he said in a BBC interview.
“It seems clear that the upward shift of the brain and compression of the surrounding tissues with ventricular expansion might not be a good thing,” Seidler says. “But, at this point, the long-term consequences to brain health and human performance are not really known.”
NASA astronaut Kate Rubins conducts a session for the Neuromapping investigation.
NASA
Staying sharp in space
To investigate how prolonged space travel affects the brain, NASA launched a new initiative called the Complement of Integrated Protocols for Human Exploration Research (CIPHER). “CIPHER investigates how long-duration spaceflight affects both brain structure and function,” says neurobehavioral scientist Mathias Basner at the University of Pennsylvania, a principal investigator for several NASA studies. “Through it, we can find out how the brain adapts to the spaceflight environment and how certain brain regions (behave) differently after – relative to before – the mission.”
To do this, he says, “Astronauts will perform NASA’s cognition test battery before, during and after six- to 12-month missions, and will also perform the same test battery in an MRI scanner before and after the mission. We have to make sure we better understand the functional consequences of spaceflight on the human brain before we can send humans safely to the moon and, especially, to Mars.”
As we go deeper into space, astronauts cognitive and physical functions will be even more important. “A trip to Mars will take about one year…and will introduce long communication delays,” Seidler says. “If you are on that mission and have a problem, it may take eight to 10 minutes for your message to reach mission control, and another eight to 10 minutes for the response to get back to you.” In an emergency situation, that may be too late for the response to matter.
“On a mission to Mars, astronauts will be exposed to stressors for unprecedented amounts of time,” Basner says. To counter them, NASA is considering the continuous use of artificial gravity during the journey, and Seidler is studying whether artificial gravity can reduce the harmful effects of microgravity. Some scientists are looking at precision brain stimulation as a way to improve memory and reduce anxiety due to prolonged exposure to radiation in space.
Other scientists are exploring how to protect neural stem cells (which create brain cells) from radiation damage, developing drugs to repair damaged brain cells and protect cells from radiation.
To boldly go where no astronauts have gone before, they must have optimal reflexes, vision and decision-making. In the era of deep space exploration, the brain—without a doubt—is the final frontier.
Additionally, NASA is scrutinizing each aspect of the mission, including astronaut exercise, nutrition and intellectual engagement. “We need to give astronauts meaningful work. We need to stimulate their sensory, cognitive and other systems appropriately,” Basner says, especially given their extreme confinement and isolation. The scientific experiments performed on the ISS – like studying how microgravity affects the ability of tissue to regenerate is a good example.
“We need to keep them engaged socially, too,” he continues. The ISS crew, for example, regularly broadcasts from space and answers prerecorded questions from students on Earth, and can engage with social media in real time. And, despite tight quarters, NASA is ensuring the crew capsule and living quarters on the moon or Mars include private space, which is critical for good mental health.
Exploring deep space builds on a foundation that began when astronauts first left the planet. With each mission, scientists learn more about spaceflight effects on astronauts’ bodies. NASA will be using these lessons to succeed with its plans to build science stations on the moon and, eventually, Mars.
“Through internally and externally led research, investigations implemented in space and in spaceflight simulations on Earth, we are striving to reduce the likelihood and potential impacts of neurostructural changes in future, extended spaceflight,” summarizes NASA scientist Alexandra Whitmire. To boldly go where no astronauts have gone before, they must have optimal reflexes, vision and decision-making. In the era of deep space exploration, the brain—without a doubt—is the final frontier.