American researchers may have come a step closer to unlocking the fountain of youth. A breakthrough in reversing cell aging could signal a revolution in regenerative medicine and longevity science.
Genetics professor and longevity expert David Sinclair and his team have devised six chemical cocktails that effectively reverse aging in mice in just over one week by rejuvenating old cells without altering their identity.
The Yamanaka factor
Shinya Yamanaka of Kyoto University stunned scientists in 2006 when he demonstrated that adult cells could be transformed back into stem cell state by injecting four specific genes known as the Yamanaka factors into them, producing an induced pluripotent stem cell (iPSC), capable of becoming any other cell in the body – something for which he shared the 2012 Nobel Prize.
Scientists have used similar techniques to reverse aging in mice, and believe it may also be possible in humans. Reprogramming human and mouse skin cells with an embryonic genome proved effective at reversing many signs of aging such as decreased lifespan and shortening telomeres; additionally, these reprogrammed cells had longer telomeres and higher levels of an enzyme that helps repair DNA damage.
To carry out their experiments, the team relied on cells from mice with progeria, an extremely rare genetic condition characterized by DNA damage, early aging and severe organ dysfunction. To avoid damaging cells further, scientists only introduced Yamanaka factors for short periods – this limited reprogramming to neurons located solely within the brain while avoiding collateral damage such as the formation of teratoma tumours when embryonic DNA enters mature cells.
Researchers added two additional Yamanaka factors – NANOG and LIN28 – to make cells even more embryonic, then transplanted them into young mice; their lifespan increased by around 20% after transplanting their reprogrammed cells; they also discovered more active mitochondria as a sign of healthy cells in these reprogrammed ones.
Researchers caution, however, that reversing aging in whole organisms remains far off. Cellular reprogramming may not be safe or practical to implement into human bodies due to large numbers of cells returning to an embryonic state and leading to cancer and organ failure.
Harvard team’s findings are nevertheless promising, with Prof David Sinclair, an expert in aging and longevity describing them as an important step forward: “This is an impressive development; if implemented into clinical settings it could revolutionise medicine – making our dreams of increasing human lifespan a reality!” Ultimately scientists hope that they can use this technique more effectively treat age-related diseases or injuries more efficiently.
The telomerase enzyme
Scientists once believed that aging resulted from DNA mutations accumulating over time, leading cells and organs to stop functioning properly and eventually die off. But recent evidence indicates this might not always be the case. Researchers have recently discovered that certain genes can extend telomeres – the protective endcaps on every chromosome – by adding small repetitive DNA sequences at either end. This process, known as telomere maintenance, is managed by an enzyme known as telomerase. Telomerase genes can be activated or deactivated by various signals from the environment; stress, radiation exposure and oxidative damage can all cause this process to slow over time and lead to reduced activity from their gene, eventually leading to shorter telomere length and cell death.
Telomerase enzyme works to counteract the shortening of chromosome telomeres by adding small repeats of DNA at each end of chromosome during replication, providing protection from their shortening over time. Over time, most organisms’ telomeres become shorter over multiple replication cycles until reaching critical thresholds where they cause cells to switch into non-replicative state or self-destruct. Researchers have identified human and mouse genes encoding maintenance factors for telomeres which may prevent such outcomes by binding tightly and stabilizing telomerase thus prolonging its activity and prolonging its activity by binding tightly and stabilizing telomerase activity and lengthening its activity by binding tightly and stabilizing it against prolonged degradation over time.
However, these factors do not exist in all cells and therefore do not adequately counteract telomere loss. Instead, some cells express high levels of the TERT gene which encodes for the reverse transcriptase component of the telomerase complex responsible for adding short sequence repeats to each telomere. GDF-11 could activate TERT expression in certain cells to effectively counteract telomere loss and reverse cellular senescence seen in aged mice; additionally it may reduce oxidative stress, inhibit degeneration, promote healthy aging while helping maintain healthy aging as well.
The epigenome
The epigenome is a collection of chemical markers that determine which genes are turned on or off, including DNA methylation and histone modifications – chemical groups which bind directly to specific sites on the genome. A cell’s epigenetic marks are determined largely by its environment: when lacking essential nutrients, pathways become active to promote efficiency and clearance while abundant resources encourage storage or irresponsible use of resources.
Harvard researchers discovered that creating temporary DNA breaks induced epigenetic changes that mimicked those experienced during early development, with their team’s reprogramming factors helping reverse them and create mice who appeared both younger and healthier than before.
Scientists have long held the belief that DNA mutations are the root cause of aging. But Harvard researchers’ work suggests otherwise: that epigenetic information becomes slowly lost as time goes by, leading to biological decline and ageing of our bodies. Their experiment is an early test of this new theory of aging.
But the results were encouraging: They showed that gene therapy cocktail they administered to older mice reversed many of the changes associated with aging and restored their youthful appearance, behavior and biomarkers of health. Scientists believe they now possess a powerful tool for studying effects of various compounds on epigenome and discovering possible reversal agents.
Though Harvard researchers’ results may seem promising, it should be remembered that this field of research is in its infancy and will take years of testing and refinement before we can provide human patients with safe and effective anti-aging treatments.
As part of a healthy lifestyle and being physically active, it is vital to prioritize living an optimal health lifestyle and staying active. According to research, physical fitness, plant-based diet, good sleep habits and healthy relationships have positive influences on our epigenome and can help reverse some aspects of aging such as cognitive decline or disease states like Parkinson’s.
The chemical cocktail
Scientists from Harvard Medical School and Massachusetts Institute of Technology may have taken significant strides toward discovering the Fountain of Youth. According to reports, their researchers believe they have discovered a chemical cocktail capable of rejuvenating cells and reversing aging; an advance that brings us one step closer towards developing life-extending drugs than ever before. Their discovery, published in Aging scientific journal, could revolutionize anti-ageing medicine as we know it – even leading to life extension pills!
Research in this area centers around the epigenome, or collection of molecules that regulates gene activity within cells. Researchers were able to reset the epigenomes of aged cells back to youthful condition; furthermore they discovered they could slow cellular aging by turning back time on nucleocytoplasmic compartmentalization (NCC), an age-related process.
Utilizing sophisticated cell-based assays, the team was able to identify specific molecules which could rejuvenate senescent cells and reduce NCC rates. After testing these compounds on laboratory mice, they successfully reversed signs of aging within just one week while doing so without uncontrolled cell growth or cancerous transformations.
Lead by genetics professor David Sinclair, his team spent three years meticulously searching for molecules to rejuvenate senescent cells and reverse cellular aging. Drawing upon previous Nobel Prize-winning research, they identified six compounds which could do just this – including anti-seizure medication such as Valproic Acid (VPA). This cocktail included drugs currently available such as Valproic Acid which treats neurological conditions including schizophrenia as well as depression.
Scientists are working towards conducting human trials of their cocktail. Until that takes place, however, public should remain cautious of any miracle cure claims involving gene therapy; developing an elixir or pill capable of actually reversing aging in living humans will take considerable time and hard work.
