The New Anti-Aging: How the pandemic has unlocked new ways to lower your biological age
While most scientists view Covid-19 as a viral respiratory disease, Nir Barzilai takes a slightly different perspective. Instead Barzilai, founder of the Research Institute on Aging at Albert Einstein College of Medicine in New York, sees it as a disease of aging. The grim statistics show he is right. In Europe, people over 60 have accounted for 90% of the victims since the beginning of August. Although the impact of Covid-19 has been universal, the elderly have been disproportionately affected. “This virus has no eyes, but it could immediately see who is older and more vulnerable,” Barzilai says. For Barzilai and other geroscientists – scientists who study the biology of aging – this presents an opportunity. They have long argued that we need a different perspective to tackle many chronic diseases, from cancer to Alzheimer’s. As all of these diseases become more common with age, geroscientists have suggested that therapies that attempt to reverse some of the cellular mechanisms of aging could make older individuals more resistant to a whole range of diseases. The premise of this approach is that while we usually measure age chronologically, the number of years we’ve been alive, your biological age says a lot more about your health. Biological age is indicated through various biomarkers ranging from telomere length – the tips of chromosomes – to changes in DNA expression and even the gut microbiome. Some 55-year-olds may be biologically equivalent to 45, making them more resistant to disease, while others may be much older, due to lifestyle or genetics. Since the 1930s, scientists have identified some drugs that appear to be capable of reversing biological aging in mice. Over the past nine months, the pandemic has provided mounting evidence that they may be able to do the same in humans. “Covid has moved anti-aging from hope to promise,” says Barzilai. “The promise is that aging is flexible and can be manipulated, which is something we have proven again and again in animals.” The eight hallmarks of aging Geroscientists have defined eight hallmarks of biological aging, which if targeted can improve the health and lifespan of animals. These hallmarks range from waning immune function, decreased quality and quantity of mitochondria – our cells’ energy factories – and a reduced ability of cells to perform waste disposal and remove toxins or viruses. There are drugs that can affect some signs of aging, including resveratrol, a compound found naturally in foods like blueberries, but the impact of Covid-19 has sparked particular interest in a cheap and commonly available drug called metformin, which has been used to treat diabetes for over fifty years, thanks to its ability to lower glucose levels. But recently, epidemiologists have begun to notice that people who take it for diabetes also appear to have reduced rates of cardiovascular disease and cancer. When the pandemic began, a first study from a Wuhan hospital sparked particular interest. It showed that diabetics who took metformin were far less likely to die from Covid-19 than diabetics who didn’t take the drug. Geroscientists all over the world have taken note. “Due to the number of people contracting Covid-19, we have been able to collect data on metformin and its impact on reducing mortality, which otherwise would have taken years to collect,” says Vadim Gladyshev, a biochemist at Harvard Medical School. Soon, further studies yielded similar results. Doctors at the University of Minnesota found that metformin reduced mortality rates in more than 6,000 Covid-19 patients with diabetes, even if only in women. Barzilai thinks he understands why. In a paper published earlier this year, it showed that metformin targets all eight hallmarks of aging simultaneously. Now, this accumulation of evidence has helped convince investors to provide $ 75 million in funding for a landmark randomized control study called TAME. Set to begin in June 2021, it aims to see if administering metformin to older people for 4-5 years can give them more years of good health. If this is successful, it could see regulator-cleared metformin as the world’s first clinically proven anti-aging therapy. Artificial Intelligence Recommendations In April, Thomas Jefferson University pharmacologist Edwin Lam was reviewing AI-based predictions of potential Covid-19 treatments and found that a drug called rapamycin was ranked higher than many alternatives. highly advertised. Rapamycin is currently used to prevent organ transplant rejection, but geroscientists have been interested in its effects on longevity for decades. It specifically targets a pathway called mTOR, which is a major driver of many of the cellular degradation processes that occur with aging. Since rapamycin inhibits mTOR, it can help reactivate different parts of the immune system, making them behave like a younger person. Boston-based biotech company resTORbio has already shown that forms of rapamycin can reduce respiratory infection rates in over 65s. They are now conducting a clinical trial in the United States, considering whether to administer rapamycin to nursing home residents on on a daily basis, it could protect them from severe Covid-19 infection. If successful, it could pave the way for rapamycin to become a new treatment to protect older people from seasonal infections and future viral outbreaks. New hopes for Alzheimer’s The renewed interest in biological aging due to Covid-19 could also bring benefits to other diseases linked to the aging process, in particular Alzheimer’s. For years, pharmaceutical companies have attempted to develop treatments that target the accumulation of amyloid proteins in the brain during the course of the disease. With Covid-19 increasing the spotlight on how aging makes people more vulnerable to disease, Alzheimer’s scientists have begun to consider alternative approaches. “I think neurologists are becoming more open to the idea that we have been too insensitive to the context of aging in which Alzheimer’s occurs,” says Jeffrey Cummings, professor of neurology at UCLA. “Most patients have their disease onset around the age of 80, where this accumulation of multiple negative influences on cognitive function accumulates.” One particular clue as to how to prevent this buildup may lie in our DNA. As we age, telomeres shorten, leading to a variety of cellular changes. However, in 1984 biologists Elizabeth Blackburn and Carol Greider discovered an enzyme produced in cells called telomerase that naturally prevents telomere shortening, a discovery that earned them the 2009 Nobel Prize. Telomerase levels also decline with age. , but in recent years, pharmaceutical companies have begun to question whether artificially increasing telomerase through drugs can prevent age-related diseases. Seoul-based pharmaceutical company GemVax has developed a product called GV1001 that increases telomerase levels in cells, with the aim of seeing if it can prevent the decline of Alzheimer’s patients and prevent the onset of the disease altogether. In a recent phase II clinical trial in patients with moderate to severe Alzheimer’s, they reported promising results on an assessment tool called the Battery for Severe Damage (SIB) scale. “The results exceeded our expectations,” said Jay Sangjae Kim, president of GemVax. With the main test – a Phase III trial due to start in 2021 – still to come, the results are to be viewed with caution, but the success of GV1001 has the potential to produce a new frontier of telomerase-based drugs for age-related diseases.