Do longevity drugs work?
Mysteriously, however, most people are loth to trade three square meals a day in the here and now for the promise of a longer retirement, so the search has been on for chemical alternatives to fasting. Two molecules in particular have attracted attention: rapamycin, an immunosuppressant used to stop the rejection of transplanted kidneys, and metformin, an anti-diabetes drug. June 19th saw the publication of a paper summarising the evidence of their effectiveness in animals, compared with fasting.
Both rapamycin and metformin have drawn the attention of the 'live for ever' brigade because they inhibit what is known as the mTOR pathway (indeed, mTOR stands for 'mechanistic target of rapamycin'). Overactivation of this in old age is associated with hallmarks of ageing such as inflammation. Conversely, fasting suppresses mTOR activity. That promotes autophagy, a phenomenon in which cells clear out their accumulated crud, which is reckoned lifespan-enhancing. Moreover, both substances also have the advantages of having undergone safety trials as part of approval for their on-label uses, and of being off-patent, and therefore cheap.
Being off-patent, however, cuts both ways. It means commercial sponsors for human clinical trials are hard to find, since they cannot monopolise sales. As a result the Targeting Ageing with Metformin (TAME) trial, a proposal sponsored by the American Federation for Aging Research, a charity, and approved by the Food and Drug Administration in 2015, remains in abeyance for lack of funds. Rapamycin, by contrast, has been tested in what is known as the PEARL (Participatory Evaluation of Ageing with Rapamycin for Longevity) trial, which began in July 2020. But this found no strong evidence that it worked.
Animal tests have proved more definitive. The new paper, published in Aging Cell by Edward Ivimey-Cook of Glasgow University and his colleagues, gathers all the vertebrate-trial evidence that the authors could find. This amounts to 167 studies on eight species, ranging from fish to monkeys. The answers seem clear-cut. To no one's surprise, calorie restriction works. So, to a pretty-much equal extent, does rapamycin. But metformin does not.
That is a blow to those, their number unknown but probably amounting to thousands, who have twisted their doctors' arms to get an off-label prescription of it for life extension. But it is a boost to those who have opted for rapamycin. These include Vinod Khosla, one of Silicon Valley's best-known venture capitalists, and, until recently, Bryan Johnson, another Californian techie, who has made a second career out of his quest for immortality. Mr Johnson, however, dropped rapamycin in 2024 because of its side-effects (abnormal lipid and glucose levels, elevated heart rate and increased risk of skin infection).
All of which is interesting. But for mere mortals who want a long and healthy life without the risk of rapamycin's side-effects the advice remains the same: eat wisely, drink moderately, exercise regularly, sleep well. And stub that cigarette out.
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NDTV
3 hours ago
- NDTV
US FDA Vaccine Chief Vinay Prasad Leaves Agency 3 Months After Appointment
Washington: The Food and Drug Administration's polarizing vaccine chief is leaving the agency after a brief tenure that drew the ire of biotech executives, patient groups and conservative allies of President Donald Trump. Dr. Vinay Prasad 'did not want to be a distraction' and was stepping down from his role as the FDA's top vaccine regulator 'to spend more time with his family,' a spokesperson for the Department of Health and Human Services said in a statement late Tuesday. Two people familiar with the situation told The Associated Press that Prasad was ousted following several recent controversies. They spoke on condition of anonymity to discuss internal personnel matters. Prasad did not immediately respond to requests for comment Wednesday morning. FDA's drug center director, Dr. George Tidmarsh, will take over Prasad's job in an acting role, according to an agency email shared with the AP. Tidmarsh started at the FDA last week after a decades-long career as a pharmaceutical executive and adjunct professor. Prasad joined the FDA in May from the University of California San Francisco, where he frequently criticized the FDA's approach to drug approvals and COVID-19 vaccines. His contrarian approach appeared to match that of his boss FDA Commissioner Marty Makary, who repeatedly praised Prasad's work and intellect. But in recent weeks Prasad became a target of right-wing activists, including Laura Loomer, who flagged Prasad's past statements criticizing Trump and praising liberal independent Senator Bernie Sanders. 'How did this Trump-hating Bernie Bro get into the Trump admin???' Loomer posted on X last week. Trump previously fired several national security officials a day after Loomer raised concerns about their loyalty. Prasad also attracted scrutiny for his handling of a recent safety issue surrounding the only approved gene therapy for Duchenne's muscular dystrophy. Under his direction, shipments of the therapy were briefly halted after a series of patient deaths, then resumed late Monday following vocal pushback from families of boys with the fatal muscle-wasting disorder. Prasad has long been skeptical of the therapy and other muscular dystrophy drugs sold by the drugmaker, Sarepta Therapeutics. As an academic, Prasad gained prominence by attacking the FDA for being too lenient in its standards for approving cancer drugs and other new therapies. That approach is at odds with Trump's Republican supporters, who generally favor speedier approvals and unfettered access to experimental treatments. During Trump's first term he signed the ' Right to Try ' law, a largely symbolic piece of legislation that won popular support from conservatives seeking to give terminal patients expanded access to unproven drugs. Prasad's decision to pause Sarepta's therapy was criticized last week by a columnist and the editorial board of The Wall Street Journal. Separately, Prasad's division issued three rejection letters this month to small biotech firms seeking approval for new gene therapies. Those drugs have been vigorously embraced by many of the anti-abortion groups in Trump's base for their potential to address intractable diseases that sometimes lead parents to terminate pregnancies. Prasad's predecessor in at FDA, Dr. Peter Marks, oversaw a dramatic rise in approvals for new gene therapies, which aim to treat or prevent disease by replacing or modifying a portion of patients' genetic code. Prasad has been an outspoken critic of Marks' leadership at FDA, which included overseeing the approval of the first COVID vaccines and therapies.
Mint
8 hours ago
- Mint
‘Combat cocktail': How America overmedicates veterans
Hundreds of thousands of veterans with PTSD have been prescribed simultaneous doses of powerful psychiatric drugs. The practice, known as 'polypharmacy," can tranquilize patients to the point of numbness, cause weight gain and increase suicidal thoughts when it involves pharmaceuticals that target the central nervous system, according to scientific studies and veterans' accounts. The VA's own guidelines say no data support drug combinations to treat PTSD. The Food and Drug Administration warns that combining certain medications such as opioids and benzodiazepines can cause serious side effects, including death. Nonetheless, prescribing cocktails of such drugs is one of the VA's most common treatments for veterans with PTSD, and the number of veterans on multiple psychiatric drugs is a growing concern at the agency, according to interviews with more than 50 veterans, VA health practitioners, researchers and former officials, and a review of VA medical records and studies. Polypharmacy has multiple definitions when it comes to central nervous system drugs. The VA defines it as taking five or more medications at the same time, while some medical researchers say it's two or more and the American Geriatrics Society defines it as three or more. There is an emerging medical consensus among VA doctors and researchers that taking multiple central nervous system drugs can wreak havoc on patients. Interactions between such drugs aren't well understood, and their effects in combination can be unpredictable and extreme. The VA maintains that the best treatment for PTSD is talk therapy. But therapists are scarce and wait times are long, so overwhelmed doctors default to pills. Because there is no single drug designed specifically to treat PTSD, veterans often end up on drug cocktails as multiple specialists try to ease a variety of symptoms and prevent harm or suicide, according to VA clinical staff, studies and veterans. 'When it comes to the challenge of polypharmacy in these populations, it's constantly chasing your tail," said Dr. Ryan Vega, a chief healthcare innovation official at the VA until 2023, who still treats veterans. 'It is where medicine is more art than science. We have medications that treat those symptoms but are we addressing the root cause?" Nearly 60% of VA patients with PTSD were taking two or more central nervous system drugs at the same time in 2019, the latest year for which data are publicly available, according to a VA study. That works out to more than 520,000 patients, up 62% from a decade earlier, driven by a near doubling of the number of VA patients with PTSD due to more combat tours and better screening. One silver lining highlighted by the study was that the percentage of PTSD veterans on five or more CNS medications declined to 7% from 12%, largely due to internal efforts to deprescribe opioids and benzodiazepines. (Central nervous system drugs affect the brain and spinal cord; psychiatric medications are a subset of CNS drugs). The VA declined requests from The Wall Street Journal to provide more recent polypharmacy numbers for veterans in its care. The VA has long been aware of the risks of overprescribing, and has internal research since at least 2016 showing the potential harms, including increased risk of suicide. The internal polypharmacy data 'was pretty concerning," said Dr. Shereef Elnahal, who headed the VA health system until early this year. He recalled a veteran advocate who told him about three veterans on more than five psychiatric drugs each who died by suicide, one after the other. They had been 'walking around like zombies" before they took their own lives, the advocate told him. The VA's use of psychiatric drugs has come under scrutiny from members of Congress and advocacy groups as the veteran suicide rate is roughly double that of U.S. adults who didn't serve. Studies by VA researchers link the simultaneous use of multiple psychiatric drugs to suicide risk among veterans, including a 2016 paper that found Iraq and Afghanistan war veterans taking five or more central nervous system drugs faced higher risks of overdose and suicidal behaviors. Yet the agency has been slow to mandate changes. It has failed to implement nationwide electronic systems to alert doctors when they prescribe multiple psychiatric drugs, despite evidence from its own studies that these alerts improve care. The VA doesn't uniformly require written informed consent for all psychiatric drugs with suicide risk, something that veterans groups and some members of Congress are urging. Some veterans who have resisted taking cocktails of drugs say they were warned by VA and military doctors that refusing them could jeopardize their eligibility for disability benefits, which can reach $4,500 a month. 'I've been mortified by practically every veteran I've seen having been prescribed multiple psychiatric medications, often without a timely referral to therapy or without any referral at all," said Janie Gendron, a therapist who worked for the Defense Department and has seen hundreds of active-duty service members and veterans in the past 25 years. Scott Griffin helps his son prepare for karate class at his home in Allison Park, Pa. A VA spokesman said the agency is looking into the issues raised by the Journal, and that the Trump administration is seeking to address serious problems it has identified in veterans' healthcare that weren't solved by the Biden administration. VA Secretary Doug Collins said at a congressional hearing in May that the agency is pursuing the potential use of alternative therapies, such as psychedelics, to offer more options and reduce the risk of suicide among veterans. The rise of the combat cocktail for PTSD has its roots in the overreliance on a single class of drugs: benzodiazepines. By the 1970s, the military and VA relied heavily on Valium and, later, Xanax as a primary treatment for traumatized service members and veterans returning from deployment. But in the 1990s, Defense Department researchers observed that high doses often yielded poor clinical outcomes, and, along with the VA, ultimately advised against their long-term use on veterans in 2004. Still, against the guideline, the VA has doled out benzodiazepines to more than 1.7 million patients with PTSD diagnoses since 2005, its own data show. It took nearly a decade for the use of those drugs to start to decline. At the same time, prescriptions to veterans with PTSD rose for other powerful psychiatric drugs. VA doctors and patients say that existing tools to limit the number of psychiatric drugs a patient takes, and guidance to avoid the use of benzodiazepines and certain antipsychotics for veterans with PTSD, are frequently ignored. After his best friend's suicide in 2013, Iraq war veteran Doug Gresenz was diagnosed with PTSD and borderline personality disorder and eventually put on six psychotropic drugs. After one medication's dosage was increased, he attempted suicide and was hospitalized. When he protested the volume of medications there, he said VA doctors questioned his commitment to recovery and told him he needed the pills to lead a normal life. 'I was guilt-tripped," he said. In 2016 alone, VA doctors prescribed him more than a dozen drugs, including antidepressants, antipsychotics, muscle relaxants and medications for nightmares, anxiety, pain and sleep, medical records show. Over little more than a decade, he received more than two dozen central nervous system medications. He recalled complaining to VA doctors that he was 'so doped up" he would have accidents before getting to the bathroom. 'I remember thinking: I'm literally poisoning myself," he said. In 2018, he quit benzodiazepines cold turkey and began to taper off the other drugs. Within a couple of weeks, he collapsed, unable to use his legs. He developed a stutter and extreme light sensitivity. Violent spasms led to another fall, which caused complications that resulted in a severe foot injury and, eventually, an amputation last year. After quitting benzodiazepines cold turkey and tapering off other drugs, Doug Gresenz collapsed. Complications from falls led to a foot injury so severe that doctors ultimately had to amputate walks back to his house with his two dogs in Aransas Pass, Texas. The VA recommends any one of three antidepressants for PTSD—sertraline (Zoloft), paroxetine (Paxil) and venlafaxine (Effexor). But doctors are free to prescribe other additional drugs off-label—and many do. 'It's super normal to see someone on five or six medications," said Mary Neal Vieten, a retired Navy psychologist who has worked with thousands of members of the military and veterans. 'That's like an everyday thing." Trauma has been medicalized, she said. 'They're acting as if the problem is in the person," she said. Instead, it's a normal response to an overwhelming experience, she said. The culture of combat cocktails begins for some who are diagnosed with PTSD while still on active duty. In the military, too, drugs have long been given priority over psychotherapy, according to many veterans, former VA officials and therapists. One Navy chaplain said his repeated calls to the Navy for more mental health resources went unanswered despite his documentation of more than 70 critical events, including suicide attempts, at a high-stress installation with nuclear submarines. When the chaplain himself grew suicidal, Navy doctors suggested that refusing the three-medication cocktail they prescribed could lead to discharge without benefits, instead of medical retirement with care. Some veterans enter VA care dependent on psychiatric drugs that they were prescribed to improve combat readiness. They include Air Force veterans given 'stop-and-go" pills—stimulants followed by sleeping pills. Michael Valentino, who was chief pharmacist at the VA until 2021, said he grew alarmed by the rising numbers of service members entering VA care on stimulants without a diagnosis justifying it. 'Then the VA has the burden of trying to undo it." A Pentagon official said several medications at once are sometimes necessary for patients with multiple medical problems or who are treatment-resistant, adding that 'records are reviewed to determine if the treating provider has provided clinical justification for the use of polypharmacy." Service members and their families are offered 'a robust and comprehensive array" of mental health programs, the official said. Psychiatric drugs work by affecting levels of chemical messengers in the brain called neurotransmitters, which send signals between nerve cells and other cells in the body. For instance, many antidepressants increase levels of serotonin, a neurotransmitter associated with mood. Benzodiazepines enhance the activity of a neurotransmitter called GABA, while some antipsychotics block dopamine receptors. Layering on several of these central nervous system agents at once can magnify their effects. Combining an antipsychotic drug that activates dopamine receptors with one that blocks dopamine can exacerbate psychosis, said Dr. Sanket Raut, a research fellow specializing in polypharmacy at Gallipoli Medical Research in Brisbane, Australia. By the same token, benzodiazepines and opioids taken together can increase the risk of overdose. 'Polypharmacy is a big problem," said Raut. 'There are many side effects: cognitive impairment, dizziness and the risk of falls." 'They give out these giant paper bags filled with medicine after your first psychiatrist appointment," said Erika Downey, a 35-year-old retired Army sergeant with PTSD. Women are more likely to be prescribed multiple drugs concurrently against guidelines, VA researchers have found. Downey's bouts of suicidal ideation while taking antidepressants, benzodiazepines and stimulants were so bad she once called a friend to come take away her gun. After that, she decided talk therapy would be the best medicine. She weaned herself off the drugs on her own over two years. She had to wait three years for a VA psychotherapy appointment. 'At the VA, you are more quick to get into a psychiatrist"—someone who can prescribe meds—'than a psychologist," she said. Erika Downey's bouts of suicidal ideation were so bad she once called a friend to come take away her hugs her daughter at home in North Carolina. Only 15% of veterans diagnosed with depression, PTSD or anxiety are offered psychotherapy in lieu of medication, according to a 2019 report by the Government Accountability Office. 'They're really leveraging the prescribing to keep up with patient demand," said Derek Blumke of the Grunt Style Foundation, a nonprofit veterans' care group. Many VA providers' impulse is to 'get them in and get them out," said Chris Figura, a patient advocate at a VA in St. Louis. Navy veteran Dick Johnson, in the VA system for three decades and diagnosed with PTSD and bipolar disorder, was prescribed more than 25 different central nervous system drugs, including antipsychotics, antidepressants and epilepsy medications, sometimes on six concurrently, his medical records show. He blames them for the collapse of his two marriages. 'They pretty much destroyed my life," Johnson said. When he worsened on one antipsychotic and experienced intense withdrawal tapering off, VA doctors tried to patch him up with a cocktail of other medicines including benzodiazepines. In 2006, he started a prolonged dose of Seroquel, a powerful antipsychotic, to get off benzodiazepines, because doctors said it was supposed to be easier to stop. His weight soared and he developed diabetes. Quitting Seroquel 'nearly killed" him, as he suffered intense vomiting, diarrhea and a near-inability to digest. He's still tapering off Paxil and Tegretol today, using a jewelry scale and sandpaper. Dr. Saraswathy Battar, a VA geriatrician, launched a passion project in 2016 to decrease the use of potentially inappropriate medications. After noticing veterans suffering from debilitating symptoms that she attributed to overprescription, she developed an electronic tool that has helped providers discontinue more than three million prescriptions. About half of VA providers are using the optional tool, she said, but they're mostly caring for older veterans or those in palliative care, while it's been hard to get mental health providers to adopt the tool. Some said they were unaware of its existence. 'Suicide and homicide get attention," but 'there's no penalty for not prioritizing polypharmacy reduction," she said. After years on psychiatric drug regimens prescribed by military and VA doctors, a growing number of veterans are taking healing into their own hands, often exploring unconventional treatments. Many veterans said they are frustrated and angry that the country spends heavily training them to be lethal, but there's little support for their fragile mental health as they reintegrate back into society. Scott Griffin, the former special operations soldier who contemplated suicide last year, reached out to a group called Veterans Exploring Treatment Solutions, or VETS, after the episode. Their suggestion: ibogaine, a powerful psychedelic derived from an African plant and illegal in the U.S., but only after tapering off his current medications. When Griffin asked his VA prescriber for help tapering, 'he point-blank refused," Griffin said. He embarked on a grueling self-taper. 'I was white knuckling. I broke my teeth from clenching," he recalled, battling intense vertigo and suicidality. After 12 hours of altered consciousness on ibogaine in Mexico, Griffin took 5-MeO-DMT, a psychoactive compound most famously found in Colorado River toads' poison, which he says was a profound spiritual experience. Since returning home in March, he has discarded his pills, prays daily and spends time with family, reconnecting after years of being 'consumed by panic and anxiety." Scott Griffin, shown relaxing after work, turned to alternative medicines for relief from his PTSD symptoms. A Stanford study of 30 special operations forces veterans published last year found that ibogaine sharply reduced PTSD and related symptoms. A bipartisan bill in the House aims to fund VA research into psychedelics, which doctors caution remain largely unproven in clinical trials. Says Griffin, 'How does bark from a tree and venom off the back of a toad beat all this crap, all these pharmaceuticals they push down your throat?" Write to Shalini Ramachandran at and Betsy McKay at
Hindustan Times
a day ago
- Hindustan Times
Why Vinay Prasad Had to Go at FDA
The Food and Drug Administration (FDA) headquarters in White Oak, Md. Vinay Prasad has left the building. The hematologist and Bernie Sanders acolyte is stepping down as head of the Food and Drug Administration's gene therapy and vaccine shop after only three months on the job. This is welcome news, but there's still reason to keep a cautious eye on the agency that could assist or stymie U.S. drug innovation in this era of great biotech advances. A Health and Human Services Department spokesperson said Tuesday night that Dr. Prasad is resigning because he doesn't want to 'be a distraction.' The truth is that he was under heavy criticism from patients and these pages for undermining the Administration's goal of fast-tracking life-saving treatments. Dr. Prasad may have been chosen for the gene-therapy and vaccine job because he found common cause with conservatives in opposing the left's Covid policies. But the White House personnel shop must have missed that the doctor has long criticized the FDA from the left. He thinks the agency approves too many drugs whose costs in his view don't justify their benefits. He wanted to turn the agency into a de facto rationing body that focuses on drug cost as much as safety and efficacy. But cost isn't the FDA's job. On Dr. Prasad's new watch, the FDA has torpedoed several promising treatments for rare and deadly diseases. This includes an immunotherapy shot that helped a third of advanced melanoma patients who had relapsed after other treatments. With these disapprovals, the agency moved its standards for drug approvals and blind-sided companies. Then came the Sarepta mugging, which we told you about on Sunday. The agency used the deaths of two boys out of nearly 1,000 who had been treated with Sarepta Therapeutics's gene therapy for Duchenne muscular dystrophy as a reason to force the drug from the market. It ignored the clear benefits in slowing disease progression. The FDA wisely backed down on Monday amid an outcry from parents and criticism in these pages. The agency's lack of clear, predictable standards under Dr. Prasad was creating enormous uncertainty for the industry, especially small biotech companies, and threatened to chill investment. Dr. Prasad's inflexible positions on the design of clinical trials also risked slowing and raising costs for drug development. This is the opposite of what FDA Commissioner Marty Makary says he wants to do. 'Why does it take over 10 years for a drug to come to market?' Dr. Makary mused Wednesday on CNBC. One reason, he said, is FDA bureaucracy. 'We don't want the FDA to be a blackbox' and 'markets want predictability.' Yes, they do. But asked about the agency's recent arbitrary rejections of therapies, Dr. Makary demurred. He also hailed Dr. Prasad as a 'genius,' noting he was a prolific author of papers—many of which argue that drugs aren't worth their cost—as if this were a mark of wisdom or the right credential to be a regulator. Dr. Makary said 'we're going to continue to talk to' Dr. Prasad, which suggests the ousted official may continue to influence agency decisions from the cheap seats. Dr. Makary said Stanford professor George Tidmarsh will lead the agency's drug reviews, which isn't reassuring. In April Dr. Tidmarsh slammed previous FDA leaders for giving 'false hope' to patients by approving experimental therapies that cost 'vast amounts of money that our health case system can ill afford.' He singled out Sarepta's Duchenne drug. This won't buoy confidence in the agency. The FDA Commissioner's public support for innovation conflicts with his personnel decisions and agency actions. Would the real Dr. Makary please stand up?
