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Friday, February 4, 2022

Is COVID Still A 'National Emergency'? Biden Must Soon Decide

 by Susan Crabtree via RealClearPolitics.com,

The omicron variant may be nearing its peak in some states, but across the country it’s produced a dizzying array of conflicting signals on whether the nation should remain under a COVID national emergency or move on to an endemic “new normal.”

Omicron, for most people without co-morbidities, produces much milder symptoms than do the coronavirus’s previous variants, but it’s far more infectious, racing through schools, shutting down classrooms and forcing parents to consult their district’s ever-shifting COVID “decision trees” on a seemingly daily basis.

“When will the emergency end?” Justice Amy Coney Barrett, a mother of seven, asked during the Supreme Court’s recent vaccine mandate hearing.

It’s a question on most people’s minds.

As the country and the world enter the third year of the pandemic, many states have moved past the worst of the omicron outbreak, but in other parts of the U.S. the tally is still rising – fueling more questions about whether people are being hospitalized and dying with COVID or because of it.

There has been no consistent national reaction, leading to even more confusion about whether omicron is the beginning of the end of COVID or just another in an endless series of variants, each with its own dangers and, possibly, silver linings.

San Francisco last week announced that it will soon replace its indoor mask mandate with a kind of honor-rule system that allows added freedom if someone is fully vaccinated and boosted, although there’s no real verification system. On the other side of the country, however, New York state’s mask mandate is back in effect after an appeals court judge issued a stay on a lower court ruling that struck it down.

Meanwhile, some school boards in Virginia are in court fighting an executive order by new Republican Gov. Glenn Youngkin that allows parents to opt their children out of local school mask mandates.

After courts struck down the federal vaccine mandate for companies with more than 100 employees, President Biden subsequently rescinded the executive order. Now Starbucks, Boeing and Delta are rehiring employees fired for refusing to get the jab. Yet, other big companies are voluntarily keeping the requirement in place even as it hurts their businesses in the middle of a labor shortage.

In a particularly worrisome sign for the depleted health care field, nurses – who still must be vaccinated or face firing – are increasingly being allowed to stay on the job if they are COVID-positive but have mild symptoms or none at all.

As more people get COVID, there’s more natural immunity throughout the population, although just how much each variant provides is hard to know. Coronavirus antibodies generated by omicron infection last at least six months in 88% of cases, according to experts, but after that period the protection rate drops to 74%. Beyond that, it’s hard to predict.

It’s a disjointed patchwork of conflicting health policies and local responses, reflecting the lack of national consensus about just how disruptive the pathogen should still be.

While calls are intensifying to transition the country into treating COVID as an endemic disease – a state where its presence is constant but predictable and manageable – the Biden administration’s top experts warn it’s too soon.

“When you have over 2,000 deaths, 150,000 hospitalizations, and you have people getting infected to the tune of somewhere around 700,000 a day, we’re not there yet,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said last week.

Fauci, the national COVID icon reviled on the right while beloved on the left, then unveiled a worst-case scenario prediction for 2022: that there could be a new variant that evades vaccines and natural immunity. “I hope that’s not the case,” he said flatly.

Other health officials and political figures are striking a more hopeful note.

President Biden last week said the U.S. hasn’t yet reached its “new normal,” but added, “We’re moving toward a time when COVID-19 won’t disrupt our daily lives, when COVID-19 won’t be a crisis but something to protect against and treat.”

Cynical conservatives argue that Biden, whose flagging poll numbers are hurting Democratic prospects in November’s midterms, is shifting his rhetoric only in an attempt to convey a sense of control and calm ahead of those elections – even though omicron is still making that shift difficult if not impossible for many Americans.

When Biden took office, his plan to stop the virus relied heavily on increasing vaccinations, safely reopening schools, and pushing stimulus bills to help states and local officials battle the pandemic. But Biden and his top officials didn’t (and possibly couldn’t) anticipate omicron and the desperate need for testing that the rapid-spreader would spur. Critics and supporters alike argue the administration’s laser focus on vaccinations, including forcing people to get shots through mandates, came at the expense of producing and distributing more tests and therapeutics.

“They frankly focused on the vaccine – the vaccine did not end up being as extinguishing as we had hoped … and so they went ahead and added the booster,” Dr. Georges Benjamin, executive director of the American Public Health Association, told RealClearPolitics.

“In emergencies, the issue isn’t whether you made a decision that turns out not to be the ideal one; the issue is how you recover – and this administration has recovered well.”

But others argue just the opposite – that Biden waited far too long to pivot to more testing, and that the tests the administration is providing every American for free will only reach most people after the omicron peak has subsided.

“The Biden administration has failed its COVID test,” declares a recent headline in the Guardian, a left-leaning British newspaper.

In Europe, where the omicron surges have peaked ahead of the U.S., officials are more optimistic and appear more determined to move on and learn to live with COVID and any variants it spawns. The top European regional official at the World Health Organization recently   that “omicron offers plausible hope for stabilization and normalization.”

British Prime Minister Boris Johnson a week ago announced an easing of coronavirus restrictions in England amid growing calls from inside and outside of his party for him to resign over his repeated violation of the rules.

Denmark, meanwhile, has announced plans to scrap all of its coronavirus restrictions and reclassify COVID-19 as a disease that no longer poses a threat to society despite infections remaining at record-high levels.

In the next month, Biden must decide whether to extend the national emergency status, which expires at the end of February. It’s a big decision with both practical and symbolic consequences. The emergency declaration, coupled with the public health emergency pronouncement issued by the Department of Health & Human Services, gives the federal government several critical tools to remove legal barriers and regulatory red tape, including the manufacturing of personal protective equipment by sources not yet completely reviewed by the Food and Drug Administration. It also allows HHS to use funding and authority under the Defense Production Act to improve onshore and near-shore production of vital resources. Additionally, it gives Federal Emergency Management Agency the ability to dispense PPE from the strategic national stockpile.

When it comes to health care providers, the emergency declarations authorize a long list of waivers from federal requirements – including expanding the type of health care professionals who can offer telehealth services billable under Medicare and Medicaid. It also allows hospitals and long-term care facilities to screen patients at locations offsite to prevent the spread of COVID.

The American Hospital Association earlier this month called on the federal government to renew both emergencies to ensure continued support for heavily burdened hospitals.

“The emergency declarations have proven critical in equipping hospitals and health systems with the tools and resources necessary to manage the recent COVID-19 surges and ensure high-quality care in this unprecedented environment,” the AHA wrote. “In their absence, the challenges of the pandemic will be exponentially more difficult to overcome.”

In mid-January, HHS Secretary Xavier Becerra extended his department’s public health emergency, continuing the declaration for another 90 days. This is the eighth time it has been extended since Becerra’s predecessor, Alex Azar, first announced it in January 2020.

But the White House hasn’t said whether it will extend the broader national emergency. A White House aide initially said he would look into the matter but didn’t respond to several follow-up questions from RCP.

Benjamin suggested Biden could follow HHS’s lead and provide just a 90-day extension instead of the year-long one he issued last year.

In addition to its practical impact on health care across the country, Biden’s decision will inevitably be politicized. Critics are likely to characterize any move to extend the emergency as proof that Biden didn’t shut down the virus as promised during his 2020 campaign – and to remind voters that the number of deaths during the first year of his presidency were similar to or only slightly less than the first year of the pandemic under Trump, despite having the vaccine in place.

Critics seized on Biden’s comments to U.S. governors in early January that there is “no federal solution” to the disease. Afterward, White House Press Secretary Jen Psaki and others tried to explain that Biden meant the federal government cannot solve the pandemic alone without working in partnership with governors and leaders at the local level.

But that explanation only poured fuel on the fire. Bobby Jindal, the two-term former governor of Louisiana, penned an op-ed for the Washington Examiner arguing that the milder omicron strain should spur a transition to endemic status.

“Emergency order expiration dates are looming,” he wrote. “… Policymakers need to relinquish emergency powers at the end of the surge and plot a sustainable path forward.”

Jindal quoted Dr. Monica Gandhi, a University of California, San Francisco infectious disease expert, who months ago predicted that COVID-19 would become endemic, like the flu, always circulating with seasonal peaks. The transition should occur when disease severity decreased and the immunity from vaccines and prior infections increased, she reasoned.

“We are amid that transition,” Jindal argued in his op-ed.

Four front-line health care providers also with UCSF agree. Last week they sent an online petition to California Gov. Gavin Newsom, all public school superintendents, and every county public health officer in the state, calling for a pivot in language that recognizes the virus as an “endemic.” This pivot, they argued, should coincide with an end to remaining restrictions, “particularly as they apply to children.”

The change.org petition had more than 30,000 signatures by Sunday evening. “We are particularly concerned about the toll that our state policies continue to have on children and teens,” the doctors wrote. “We are writing to ask California officials to acknowledge the endemic nature of COVID-19 after the omicron surge and immediately shift our public dialogue toward defining a path for removing all remaining COVID-19 restrictions in public schools.”

In addition to promising to shut down COVID, the Biden administration pledged to let scientists and public health experts drive its pandemic strategy. But omicron has produced such differing opinions among health experts and scientists that it’s scrambled the plan to have consistent and authoritative public policies, according to some health experts.

Lindsay F. Wiley, a health law professor at UCLA, said recent missteps by the CDC have once again damaged public trust and reinforced public perception that the administration’s guidance is “pretty chaotic.”

“There’s confusion after the CDC changes its guidance, and [it] has not always provided a robust explanation or justification for that change,” she told RCP, noting the back-and-forth on mask guidance and more recent changes governing isolation and quarantine that at first did not incorporate any kind of testing.

But, “the national emergency [declaration] is a much different framework than most people assume,” Wiley added, “so [it’s] still playing an important role and is still an appropriate measure in my opinion.”

Benjamin agreed, although he recommends Biden extend it for only a few months at a time, instead of continuing the declaration for a full year. Potential new variants are developing, and though Benjamin said they thus far don’t seem too worrisome, he warned of unpredictable twists and turns ahead.

He described three possible future COVID scenarios. The worst-case one, as Fauci outlined, would involve the development of an extremely infectious and lethal variant similar to delta. Another possibility is more seasonal outbreaks of COVID, as with the flu. And the third, he said, are spats of reoccurring lethal outbreaks in different states, which would require resources being moved around to put those fires out.

“We're still tracking other new variants that are developing day by day,” he said. “We don't think that there are problems, but this is going to be an issue for a while.”

https://www.zerohedge.com/political/covid-still-national-emergency-biden-must-soon-decide

Quebec discovery could help decrease the mortality rate of COVID-19

 A researcher in Quebec hopes to have achieved a breakthrough in COVID-19 research that could lead to a better immune response for those infected with the novel coronavirus, and ultimately help lower the mortality rate.

Jérôme Estaquier, a researcher at the Université of Laval Research Center in Quebec City, has been working in the field of AIDS research for 30 years.

Estaquier and an international team found that the reduction and loss of T lymphocytes (T cells), which is a type of white blood cell, is the same in those with COVID-19 and those who have AIDS.

“We found that those with COVID-19 that are in the intensive care unit develop abnormal lymphocyte cell life, suggesting that this may have an impact for an individual against COVID-19,” Estaquier said.

“During COVID infection, 60 per cent of patients develops lymphopenia, which means that we are losing lymphocytes, which are essential to fight microbial viruses like COVID-19. So if you are losing lymphocyte it impacts the person to develop a strong immune response.”

T lymphocytes cells are vital to destroying any virus that enters the body. With the rapid death of these cells, those infected with COVID do not have an adequate immune response.

With this discovery, Estaquier says we can be more proactive for those with COVID-19 in intensive care.

“They are able to use a small compound to restore and to prevent cell death in COVID-19 patients. So by suggesting that we are improving the capacity of T cells in someone, this may have some beneficial effect in the immune response against COVID.”

The research team believes this could allow for early treatment to support the immune defence for those with AIDS as well.

“This is our next step, of course, to develop a clinical trial to assess whether the compound that we have written about in this manuscript can prevent immune deficiency that we observe in the severe disease of a patient.”

Estaquier says he hopes his research will be sustained and funded, as this discovery is important to provide a new therapeutic approach, one that will allow for a better immune response for those who would otherwise be in critical care.

The research was published in the journal “Cell Death and Differentiation.”

https://montreal.citynews.ca/2022/02/02/quebec-discovery-mortality-covid19/

Iowa COVID-19 dashboard to be decommissioned in Feb. as emergency proclamation expires

 Iowa will soon decommission its COVID-19 websites, after Governor Kim Reynolds signed the final extension of the state's Public Health Disaster Emergency Proclamation, her office announced Thursday.

The Public Health Disaster Emergency Proclamation, which will now expire on February 15, was first issued on March 17, 2020, and included provisions related to pandemic response. Reynolds says that the remaining provisions in the proclamation focus on addressing workforce issues, which would be better addressed by legislation and other more permanent solutions.

The state says that Iowa is not alone in ending its public health proclamation, as almost half of all states have already discontinued theirs.  

The state says that its COVID-19 dashboard (coronavirus.iowa.gov) and its vaccine resources website (vaccinateiowa.gov) will now be decommissioned on February 16. However, certain COVID-19 data points will still be available on the IDPH website

Reynolds says that the state will begin to manage COVID-19 similar to how it manages and tracks the flu.

“We cannot continue to suspend duly enacted laws and treat COVID-19 as a public health emergency indefinitely. After two years, it’s no longer feasible or necessary. The flu and other infectious illnesses are part of our everyday lives, and coronavirus can be managed similarly,” Reynolds stated. “State agencies will now manage COVID-19 as part of normal daily business, and reallocate resources that have been solely dedicated to the response effort to serve other important needs for Iowans.” 

The data still reported on the IDPH website (idph.iowa.gov) will include information on positive tests, cases by county, deaths, and vaccinations. The state asserts that this will create greater efficiency and help staff get back to their original roles. 

According to Garcia, in a press meeting following the announcement, a number of IDPH staff are tied up managing the data, and could be better used elsewhere. She cited for an example, the increased number of suicides being seen in central Iowa.

“While our COVID-19 reporting will look different, Iowans should rest assured that the state health department will continue to review and analyze COVID-19 and other public health data daily, just as we always have,” IDPH Director Kelly Garcia stated. “The new format will include data points that Iowans are used to seeing, but moves us closer to existing reporting standards for other respiratory viruses. This new phase also assures that our teams, who have been deeply committed to the COVID-19 response, can return to their pre-pandemic responsibilities, and refocus on areas where the pandemic has taken a hard toll.” 

At the press meeting following the announcement reporters asked Garcia if Iowa was now looking at COVID-19 as an endemic disease rather than a pandemic. 

"Yes ultimately that will be the case. We aren't there yet because that means steady, and we are still on the downside of a peak, thankfully on the downside," said Garcia. "Every indicator tells us that we peaked a couple of weeks ago, maybe 10 days ago, around the 18th of last month. But we'll need to hold steady to meet that definition.

Iowa will still be reporting COVID-19 data to the CDC, which will continue to provide some state-level data. The State Hygienic Lab will also continue to operate its at-home testing program. 

Because it's not a prerequisite, Iowa will still receive federal coronavirus-related funds without a disaster proclamation in place. 

https://www.kwwl.com/coronavirus/iowas-covid-19-dashboard-to-be-decommissioned-in-february-after-reynolds-will-let-emergency-proclamation/article_7a242834-8528-11ec-8d26-2bb651161493.html

IRADIMED CORPORATION 2021 Financial Results and Guidance

 Year Ended December 31, 2021

For the year ended December 31, 2021, the Company reported revenue of $41.8 million compared to $31.7 million for the same period in 2020. Net income was $9.3 million, or $0.74 per diluted share, compared to $1.4 million, or $0.11 per diluted share for the same period in 2020. The increase in net income and diluted earnings per share is primarily the result of a $10.1 million increase in revenue and a $2.5 million decrease in general and administrative expenses, partially offset by a $2.5 million increase in income tax expense for the year ended December 31, 2021. During the year ended December 31, 2020, the Company recognized total general and administrative expense of $3.2 million related to our former CEO.

Non-GAAP net income was $10.4 million, or $0.83 per diluted share, for the year ended December 31, 2021, and excludes $1.1 million of stock compensation expense, net of tax expense. Non-GAAP net income for the year ended December 31, 2020 was $5.0 million, or $0.40 per diluted share, which excludes $1.3 million of on-going stock compensation expense, net of tax, and $2.4 million of expenses, net of tax, related to the separation of our former CEO.

Financial Guidance

For the full year 2022, the Company expects to report revenue of $51.4 million to $52.2 million, GAAP diluted earnings per share of $0.82 to $0.90, and non-GAAP diluted earnings per share of $0.91 to $1.01, which assumes a normalized tax rate.

For the first quarter 2022, the Company expects to report revenue of $12.1 million to $12.3 million, GAAP diluted earnings per share of $0.16 to $0.18, and non-GAAP diluted earnings per share of $0.20 to $0.21, which assumes a normalized tax rate.

The Company’s non-GAAP diluted earnings per share guidance excludes stock-based compensation expense, net of tax, which the Company expects to be approximately $1.4 million and $0.3 million for the full year and first quarter 2022, respectively.

https://www.biospace.com/article/releases/iradimed-corporation-announces-fourth-quarter-2021-financial-results/

UCB: Positive data in myasthenia gravis with zilucoplan phase 3 study

 

- Positive topline results show the Phase 3 RAISE (NCT04115293) zilucoplan trial met primary and all key secondary endpoints in adults with generalized myasthenia gravis
- The results show a favorable safety profile and good tolerability
- UCB plans to proceed with zilucoplan regulatory submissions later this year
- Results follow recent positive topline data from the Phase 3 MycarinG study investigating rozanolixizumab, a monoclonal antibody also being developed by UCB in the same indication
- These results are the latest in a series of positive phase 3 data announcements by the company across its product pipeline

Financials Indicate Novartis’ Sandoz Division Could Be a Tough Sell

 Novartis reported its full-year financials this week for 2021, and overall, the news was good. Full-year net sales grew 4%, fourth-quarter sales were up 6% and operating income increased 13%. Of concern, however, is the company’s Sandoz generics unit. Net sales were $2.5 billion, with volume adding 11% to growth, but pricing impacting knocked off 9%. European sales were 4% and U.S. sales dropped 8%.

The company is currently running a strategic review of Sandoz with the possibility of a sale. But Novartis expects revenue for Sandoz to continue dropping in the U.S. this year, which will make it a difficult sell. The asking price is likely to be $25 billion or more, although the company has yet to decide which parts will be on the market. Insiders say part of the issue is that some of Sandoz’s production is so thoroughly tangled with other parts of Novartis’ business it can be hard just to split off products.

Richard Saynor, chief executive officer of Sandoz, provided more context, saying, “As we go into 2022, we’re seeing good growth from the rest of the world. And really, the challenge continues to be the U.S. And that’s slowly— the impact of price clearly drives the issues in the U.S., but we’re slowing stabilizing. And so really I see 2022 is a year where the rate of decline in the U.S. does stay low, but it does drag down the overall business.”

In the company’s report, Chief Executive Officer Vas Narasimhan said he would decide on Sandoz by the fourth quarter but keeping all options open in the meantime. Narasimhan told Bloomberg Television that the division has picked up “a lot of interest” from private equity firms and other generic drug companies. “We still need to see, of course, concrete proposals. It’s all in flux at the moment. We’re very much in a position of listening.”

Meanwhile, Narasimham has indicated the company is “aggressively defending each group of patents” on its cardiovascular blockbuster, Entresto. Entresto sales climbed 40% over the year. Additional growth drivers were Cosentyx, which jumped 17%, Zolgensma, which rocketed 46%, Promacta/Revolade (15%) and Kisqali (36%).

Narasimhan stated, “Novartis delivered another year of solid operational performance with mid-single-digit top-line growth, margin expansion, and strong free cash flow. Our in-market growth drivers continue to perform well across geographies, supporting our confidence in our mid and long-term growth outlook. Despite some pipeline setbacks, we delivered important innovation milestones including Entresto, 177Lu-PSMA-617, iptacopan, Kisqali, and Leqvio.”

Continuing, he said, “Looking ahead, we are focused on delivering on our pipeline and key technology platforms, which includes 20+ potential assets with significant sales, to be approved by 2026. We remain balanced in our capital allocation priorities as we continue to invest in innovation alongside returning capital to our shareholders.”

One big plus for the company is it sold its investment in Roche Holding AG for $20.7 billion. Using the proceeds and a strong Free Cash Flow, the company repaid $23.6 billion of its debt last year.

That’s the sort of combination that has investors and analysts asking the company if it plans any big mergers and acquisitions (M&A). Narasimhan basically said no when asked if the company would do a larger M&A, meaning $30 billion or larger.

“Our focus is bolt-on. Bolt-on deals, most of the deals we’ve done, as I mentioned earlier, have been sub-$1 billion upfront with payouts for the total deal value of less than $2 billion, as in recent times, including the four deals that we recently signed. And we continue to focus our energies there. We look at larger assets,” said Narasimhan.

https://www.biospace.com/article/novartis-sandoz-division-may-be-a-tough-sell/

Is There a Cure for Aging?

 Heart disease. Cancer. Diabetes. Dementia.

Researchers spend billions of dollars every year trying to eradicate these medical scourges.


Yet even if we discover cures to these and all other chronic conditions, it won't change our ultimate prognosis: death.


"That's because you haven't stopped aging," says Jay Olshansky, PhD, a professor of epidemiology and biostatistics at the University of Illinois at Chicago School of Public Health.


But what if we could? What if we are trying to extend longevity in the wrong way? Instead of focusing on diseases, should we take aim at aging itself?


Some scientists think so. Fueled in part by a billion dollars of investor money, they are attempting to reverse-engineer your molecular biological clock. Their goal? To eliminate not merely diseases that kill people, but to prevent death itself.

Hacking the Code for Immortality

Aubrey de Grey, PhD, a biomedical gerontologist, has drawn wide attention for his belief that the first person who will live to be 1,000 years old is already among us.

He believes there's no cap on how long we can live, depending on what medicines we develop in the future.

Dr Aubrey de Grey

"The whole idea is that there would not be a limit on how long we can keep people healthy," de Grey says. He's the chief science officer and co-founder of the SENS Research Foundation, which funds research on how to put the brakes on aging.


De Grey's view, in theory, isn't so far-fetched.

Scientists have studied the immortal jellyfish, Turritopsis dohrnii. It's the only animal that can cheat death by reverting from adulthood back to its polyp stage when threatened with danger or starvation.


Other clues to possible eternal life also may exist underwater. Certain marine clams can live more than 500 years. And lobsters stock a seemingly limitless supply of a youthful enzyme that has some scientists wondering if the crustacean, under the best conditions, just might live forever.


Some day, anti-aging drugs may 'eliminate damage from the body by resetting or turning back the clock.' Dr Aubrey de Grey, biomedical gerontologist

Among humans, researchers have been studying "super-agers" — people who not only live exceptionally long, but also do so without many of the chronic diseases that plague their peers. That's even though they share some of the same bad habits as everyone else.

"They are making it past the age of 80 with their minds completely intact. That's what's so unusual," Olshansky says. The rest of their bodies are doing better than those of average 80-year-olds, too.

People who reached ages 95 to 112 got cancer, heart disease, diabetes, osteoporosis, and stroke up to 24 years later than those with average lifespans, data show. Figuring out why might pave the way for targeted gene therapy to mimic the DNA of these nonagenarians and centenarians.


"There's likely to be secrets contained within their genome that are eventually discovered that will help us develop therapeutic interventions to mimic the effects of decelerated aging," Olshansky says.


Treating aging this way may offer a bigger payoff than targeting individual diseases. That's because even if you manage to dodge any illnesses, there's ultimately no escaping old age.

"Longevity is a side effect of health," de Grey says. "If we can keep people healthy, then their likelihood of dying is reduced."

Aging as a Preventable Condition

In 2015, Michael Cantor was prescribed metformin for prediabetes. Once that was under control, his doctor said Cantor could quit the drug. But Cantor had heard about studies testing it as an anti-aging drug. The 62-year-old Connecticut-based attorney asked if he could stay on it. A year ago Cantor's wife, Shari, who is mayor of West Hartford, CT, started to take metformin, too.

"I read the articles, they made a lot of sense to me, and with the number of people that have been taking this drug worldwide for decades, I felt like there was nothing to lose," he says.

The couple can't say if their daily doses have led to any changes in how they look or feel. After all, they're taking the pills not to treat current ailments but to prevent ones in the future.

Dr Nir Barzilai

They may have answers soon. Nir Barzilai, MD, director of the National Institutes of Health's Nathan Shock Centers of Excellence in the Basic Biology of Aging, is leading a study that hopes to prove aging is a preventable health condition. The TAME (Targeting Aging with Metformin) study is designed to do this by demonstrating that metformin, a cheap and widely prescribed pill for diabetes, may also be an anti-aging elixir.


If the results are what they think they will be, the whole world could go on metformin and extend life for everybody. Dr Nir Barzilai, lead researcher on Targeting Aging with Metformin study

The TAME trial is currently in phase III — typically the final step of research into any treatment before drugmakers can apply for FDA approval.

Earlier studies found that people with type 2 diabetes who take metformin have lower death rates from any cause, compared to peers who don't take the drug. Metformin also seems to help curb incidence of age-related diseases, including heart disease, dementia, and Alzheimer's. It also may lower the risk of many types of cancer as well as raise the chances of survival. Observations made since the beginning of the COVID-19 pandemic suggest that people who get the virus while taking metformin are less likely to land in the hospital or die from it.



It's not clear exactly how metformin works to do all that. The compound was originally derived from Galega officinalis, also known as goat's rue, a perennial plant used as medicine since medieval times.

Barzilai says he hopes to prove that aging is a preventable condition.

"If the results are what they think they will be, the whole world could go on metformin and extend life for everybody — extend your good quality of life," Barzilai says. "That's what we all want. Every extra year that we could get where we're still vigorous and vital would be amazing."

Long Life vs Healthy Life

Some researchers argue that only the "healthspan" — the period of life free of illness — is worth extending. Of course, a healthy lifestyle can add years to most people's lives and actually improve cellular aging. Some of the biggest payoffs come from quitting or never smoking, logging more than 5½ hours of physical activity per week, and keeping a normal weight.

Drugs may be able to do that as well by interrupting common markers of aging, including telomere length, inflammation, oxidative stress, and slower cell metabolism.

"You don't have to target all of these hallmarks to get improvement" in healthspans, says Barzilai, who also is director of the Institute for Aging Research at the Albert Einstein College of Medicine in the Bronx and scientific director of the American Federation for Aging Research.

"If you target one, you show benefit in the others."

The medical term for growing old is senescence. Buffeted by DNA damage and stresses, your cells deteriorate and eventually stop multiplying, but don't die.

That slowdown may have big consequences for your health. Your genes become more likely to get mutations, which can pave the way for cancer. Mitochondria, which produce energy in the cell, struggle to fuel your body. That can damage cells and cause chronic inflammation, which plays a part in diabetes, arthritis, ulcerative colitis, and many other diseases.

One major hallmark of aging is the growing stockpile of these senescent cells. Damaged cells become deactivated as a way to protect your body from harmful or uncontrolled cell division. But like the rotten apple that spoils the whole bunch, senescent cells encourage their neighbors to turn dysfunctional, too. They also emit proteins that trigger inflammation. Your body naturally removes these dormant cells. But older immune systems have a harder time cleaning up, so the senescent cells are more likely to hang around.

Flushing out this accumulated debris may be one way to avert aging, some experts say.

De Grey also believes that could be done with drugs.

"These therapies would actually repair [cellular] damage," he says. "They'll eliminate damage from the body by resetting or turning back the clock."

James Kirkland, MD, PhD, of the Mayo Clinic is one researcher exploring this theory. He gave a mixture of the cancer drug dasatinib and a plant pigment called quercetin to people with diabetic kidney disease. Quercetin is an antioxidant that gives grapes, tomatoes, and other fruits and vegetables their flavor.

A small phase I clinical trial showed that the dasatinib-quercetin combination got rid of senescent cells in the tissues of people with the disease.

The researchers don't know yet if the results will translate into prolonged youth. They also don't know how high a dosage is needed and what long-term problems the treatment might cause. People with chronic leukemia take dasatinib for years with few serious ill effects.

In another recent study, scientists used oxygen therapy to tackle senescent cells. Thirty-five adults ages 64 and older received oxygen therapy in a pressurized chamber. After 60 daily sessions, they showed a decrease in senescent cells and improvement to the length of DNA segments called telomeres. Shortened segments of telomeres are thought to be another marker of aging.

Researchers are also looking to the gene editing technology CRISPR for anti-aging treatments, but the testing is only in mice so far.

Barzilai hopes that if the metformin trial succeeds, it will open the floodgates to a wave of new drugs that can stop or reverse human aging. Some of the major players in this field include Juvenescence, AgeX Therapeutics, LyGenesis, and Life Biosciences, which Barzilai founded.

"Until aging is seen as preventable, health plans won't have to pay for this type of treatment," he says. And if health plans won't cover aging, pharmaceutical companies have little incentive to invest in drug development.

That may be the only thing standing between humans and unprecedented lifespans. The Census Bureau projects that Americans born in 2060 should live an average of 85.6 years, up from 78.7 years in 2018. De Grey's prediction tops that mark by a factor of about 50. He believes that the life expectancy for someone born in 2100 may well be 5,000 years.

Barzilai, for his part, has a prediction that's seemingly more modest.

"We die at 80. Getting an additional 35 years is relatively low-hanging fruit," he says. "But I don't believe that is a fixed limit."

https://www.medscape.com/viewarticle/967916