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.
Saliva May Help Diagnose PTSD in Veterans
As a bioinformatician and young veteran, Guy Shapira welcomed the opportunity to help with conducting a study to determine if saliva can reveal if war veterans have post-traumatic stress disorder, or PTSD.
The research team, which drew mostly from Tel Aviv University’s Sackler Faculty of Medicine and Sagol School of Neuroscience, collected saliva samples from approximately 200 veterans who suffered psychological trauma stemming from the years they spent fighting in the First Lebanon War in 1982. The researchers also characterized the participants’ psychological, social and medical conditions, including a detailed analysis of their microbiomes.
They found that the former soldiers with PTSD have a certain set of bacteria in their saliva, a distinct microbiotic signature that is believed to be the first biological marker for PTSD. The finding suggests that, in the future, saliva tests could be used to help identify this disorder. As of now, PTSD is often challenging to diagnose.
Shapira, a Ph.D. student at Tel Aviv University, was responsible for examining genetic and health-related data of the veterans who participated – information that had been compiled steadily over four decades. The veterans provided this data voluntarily, Shapira says, at least partly because the study carries important implications for their own psychological health.
The research was led by Illana Gozes, professor emerita of clinical biochemistry. “We looked at the bacteria in their blood and their saliva,” Gozes explains. To discover the microbial signatures, they analyzed the biometric data for each soldier individually and as a group. Comparing the results of the participants’ microbial distribution to the results of their psychological examinations and their responses to personal welfare questionnaires, the researchers learned that veterans with PTSD – and, more generally, those with significant mental health issues – have the same bacterial content in their saliva.
“Having empirical metrics to assess whether or not someone has PTSD can help veterans who make their case to the Army to get reparations,” Shapira says.
More research is required to support this finding, published in July in Nature’s prestigious Molecular Psychiatry, but it could have important implications for identifying people with PTSD. Currently, it can be diagnosed only through psychological and behavioral symptoms such as flashbacks, nightmares, sleep disorders, increased irritability and physical aggressiveness. Veterans sometimes don’t report these symptoms to health providers or realize they’re related to the trauma they experienced during combat.
The researchers also identified a correlation that indicates people with a higher level of education show a lower occurrence of the microbiotic signature linked to PTSD, while people who experienced greater exposure to air pollution show a higher occurrence of this signature. That confirms their finding that the veterans’ health is dependent on their individual biology combined with the conditions of their environment.
“Thanks to this study, it may be possible in the future to use objective molecular and biological characteristics to distinguish PTSD sufferers, taking into account environmental influences,” Gozes said in an article in Israel21c. “We hope that this new discovery and the microbial signatures described in this study might promote easier diagnosis of post-traumatic stress in soldiers so they can receive appropriate treatment.”
Gozes added that roughly a third of the subjects in their study hadn’t been diagnosed with PTSD previously. That meant they had never received any support from Israel’s Ministry of Defense or other officials for treatment and reparations, the payments to compensate for injuries sustained during war.
Shapira’s motivation to participate in this study is personal as well as professional: in addition to being veteran himself, his father served in the First Lebanon War. “Fortunately, he did not develop any PTSD, despite being shot in the foot...some of his friends died, so it wasn’t easy on him,” says Shapira.
“Having empirical metrics to assess whether or not someone has PTSD can help veterans who make their case to the Army to get reparations,” Shapira says. “It is a very difficult and demanding process, so the more empirical metrics we have to assess PTSD, the less people will have to suffer in these committees and unending examinations that are mostly pitched against the veterans because the state is trying to avoid spending too much money.”
The Friday Five Weekly Roundup in Health Research
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the promising studies covered in this week's Friday Five:
- The right facial expression for your mental health
- Can virtual reality reduce pain?
- Lab made blood vessels
- Gene editing muscles to lower blood sugar
- A magic ingredient coming from exhaust vents