Scientists at Harvard have made considerable strides toward discovering a Fountain of Youth. By altering laboratory mice epigenomes, they’ve managed to reverse signs of aging.
Epigenetic changes, or chemical modifications to DNA that alter gene activity without altering its sequence, were recently published in Cell. The findings can be seen here.
What are they?
Scientists have made major strides toward discovering the proverbial Fountain of Youth after rejuvenating worn-out organs in elderly mice. A team from Harvard University reversed the aging process for these creatures, restoring their sense of smell, ability to reproduce, and memory capabilities – potentially opening the way towards treatments that extend human lifespan and slow age-related diseases.
Researchers utilized CRISPR gene editing technology to produce temporary yet quickly healing cuts in mice’s DNA, mimicking daily cell damage that causes epigenetic changes that accelerate aging processes – all without permanent consequences or irreversibility, according to researchers.
After cutting cuts in their mice’s DNA, scientists injected them with a combination of three Yamanaka factors that reversed epigenetic changes that had taken place and made them look and act younger; it also promoted cell production in their muscles, kidneys and eyes.
Researchers are exploring whether similar techniques could be applied to humans. Their hope is that such therapies could extend people’s lives and improve their quality of life.
Harvard team’s bold claim may seem far-fetched, but their evidence to back them up speaks for itself. Their studies on various tissues and organs, such as optic nerve, brain tissue, kidney and muscle have yielded promising results; plus they recently documented improved vision and longer lifespans among monkeys.
Scientists from HMS’ Sinclair Lab believe that epigenetics rather than mutations are at the core of how humans and other mammals age. Their research indicates that chemical exposure such as smoking cigarettes may induce epigenetic changes that lead to premature aging in people and other mammals.
Researchers conducted their latest study by injecting older mice with a molecule that activated the genetic switch that keeps telomeres from becoming shorter over time. Normally turned off in adult cells as an evolutionary compromise to avoid cancer, activating this gene restores its functionality and delays cell aging caused by shrinking telomeres.
How did they do it?
Harvard scientists used temporary DNA “cuts” that mimicked lifestyle and environmental effects to alter mice epigenetic patterns; this led them to age much faster than expected with signs of frailty and tissue degradation as well as high levels of biomarkers that indicate age like DNA damage and accumulation of toxins.
The team administered gene therapy to reverse the epigenetic changes they’d caused. This reinstated genes responsible for keeping telomeres long and slowing aging; as a result, their cells became younger and less damaged than before.
Scientists generally agree that most aging processes are determined by epigenetics rather than mutations to our genetic code that lead to cancer and other diseases. Since the discovery of Yamanaka factors, several labs have used these factors to reverse aging in mice; but Harvard study marks the first attempt without resorting to surgically joined parabiotic systems involving younger mice being placed with older ones.
Researchers have shown that the ICE technique can rejuvenate cells in mice’s retina, brain, muscle and kidneys – although researchers still need to find an efficient method of applying gene switch evenly throughout all cells so the whole body is restored simultaneously.
Even though this research is encouraging, longevity experts remain doubtful that there will be a definitive cure for aging any time soon. Dr. Luigi Fontana of the Manual of Healthy Longevity & Wellbeing notes that while biological aging might seem out of our grasp for now, there are other steps we can take to increase lifespan – like eating a balanced diet with nutritious foods like herbs and spices; engaging in moderate exercise; relieving stress levels by managing emotions better and getting enough restful sleep each night.
Another challenge in the research involved mice having an extra gene called hTERT that produced telomerase, an enzyme that prevents their telomeres from shortening too quickly and initiating senescence. While humans possess this same gene, its activation has been blocked as it could allow cancer cells to proliferate unchecked and cause tumors; researchers have attempted reactivating it but so far without success.
What are the results?
Scientists have developed an innovative technique that reverses cell aging without altering DNA, potentially revolutionizing treatments for age-related diseases and improving regenerative medicine practices – while also moving us closer towards our dream of whole-body rejuvenation.
Scientists made their breakthrough by breeding mice with genetic mutations that caused them to lack an enzyme called telomerase, which prevents chromosome ends from shortening with each cell division and eventually leading to organ and tissue degeneration as we get older. When scientists activated this mutant mouse strain’s switch for telomerase production they saw complete reverse of all signs of aging such as decreased smell sensitivity, shrinking brains, infertility, damaged spleens and intestines as well as aged-looking organs.
Researchers recently published in Aging their success at turning back time on aged mice by activating quiescent adult stem cells and reinstating telomerase. Reactivated adult stem cells then produced new neurons as well as myelin sheaths which surround nerve cells; both features that had thinned in older animals. Furthermore, animals showed improved exercise ability, with their olfactory systems back to normal functioning – turning back the clock!
Researchers devised a new tool to assess biological age of mice rather than chronological age, by counting how many sites on their genome lost methyl groups used for controlling gene activity – older mice lost more methyl groups over time as more sites lost them than younger ones did. They then injected each mouse with an OSK virus containing OSK genes to activate telomerase, thus reversing ageing processes.
The mice regained their olfactory function, increased exercise capacity and became fertile once again. Their hearts returned to normal health while their spleens and intestines were repaired; furthermore, their olfactory system in their brains was also restored as their skeletal muscles returned to youth status. Now, our team is exploring whether this OSK technique can be replicated across other mouse models as well as potential human candidates.
What are the implications?
Researchers from Harvard Medical School have created a chemical cocktail to reverse the aging of mice by rejuvenating old cells within muscles, tissues, and organs. They did so through epigenetics – altering how genes work instead of changing DNA sequence – which has shown their results can affect aging as much as genetic mutations do. Their results, published January 12th 2019, demonstrate this fact.
Harvard researchers worked with the mouse telomerase gene, which helps maintain protective caps at the ends of chromosomes. Each time cells divide, their protective caps shorten with each cell division until eventually they cause self-destruction or become too damaged for normal function – this process is known as cellular senescence and contributes to many symptoms associated with aging like reduced immunity, infertility and cognitive decline.
Researchers engineered a mouse telomerase gene with switchable off/on capabilities in order to produce mice with short telomeres, then gave the animals six chemical cocktails that reversed key signs of aging by rejuvenating senescent cells without altering normal function or altering cellular identity. Their research suggests these chemicals might work for people as well; however, raising levels of telomerase would increase cancer risks significantly.
Harvard team’s experiment to turn back time in laboratory animals ran into difficulties as it wasn’t known whether induced DNA breaks mirrored natural ones, making it hard to prove they caused any reversal in aging in mice. A similar strategy is employed by rejuvenation-focused company Rejuvenate under Noah Davidsohn – who participated in this research study as their Chief Scientific Officer.
Rejuvenate is working on a pill to deliver epigenetic factors to activate telomerase and other key genes, and hopes to conduct human trials within 10 years. Other experts remain dubious of Rejuvenate’s “antiaging” therapies due to ample information available about how best to slow aging – such as eating healthier, exercising regularly and getting adequate rest.
