Researchers in the Sinclair lab employed a new tool to measure how old ICE mice were not chronologically, but biologically. They discovered that chemical cocktails and iPSC reprogramming successfully reversed age-related gene expression patterns associated with cell senescence.
Mammalian cells contain backup copies of epigenetic software to reset chromatin structures and restore youthful gene expression patterns, providing mammalian cells a protection mechanism against cell age-related damage. Reducing calories has been found to extend lifespan in worms, fruit flies and rodents.
Epigenetics
Researchers have long held the belief that mutations to DNA encoding genes–called mutations–are one cause of aging. But a recent Harvard Medical School study suggests epigenetic changes affecting how genes are turned on or off also play an integral part in this process, with chemically reversing such epigenetic changes having the power to slow or even reverse effects of aging, with these findings appearing in Cell journal.
Our bodies contain 3 billion DNA base pairs, and although all cells in our bodies share identical genes, their expression may differ due to different roles they fulfill and environmental changes. Epigenetic marks serve as bookmarks that enable cells to access and read genetic code faster. They signal when genes should turn on or off; this process of gene regulation determines how fast or slow our bodies grow or respond to certain signals.
Researchers discovered that adding Yamanaka factors to cells with epigenetic marks switched off aging mechanisms and caused them to behave as though they were younger – they grew faster and were more likely to divide. Furthermore, rejuvenation was shown with senescent cells (cells that have stopped growing or are no longer actively dividing), thought to contribute to tumor development or inflammation conditions.
Scientists developed what’s known as an artificial epigenetic clock for mice. By measuring how quickly cells started losing methyl groups, the scientists determined an artificial epigenetic clock could be constructed. By administering OSK cocktails they found they could reverse this effect and slow cellular aging by rejuvenating senescent cells and rejuvenating old ones.
The team is currently exploring whether these chemicals can be used to treat human patients suffering from diseases associated with premature aging and senescence, such as cancer, Alzheimer’s disease or cardiovascular disease. In order to do this, they will first conduct trials utilizing OSK cocktails among larger human populations.
Gene Therapy
Recently, gene therapy had its limits constrained by your immune system rejecting newly introduced genes through gene therapy techniques. But scientists recently developed an innovative technique to circumvent this rejection through using natural mechanisms that obscure new genes within body cells and protects them from their immune response systems – opening up possibilities of gene therapy to any kind of therapeutic gene.
In a new study, researchers used this approach to search for molecules that, when combined, rejuvenate human cells. They identified six chemical cocktails which restored compartmentalization of nucleocytoplasmic proteins (a marker of youth) and reversed transcriptomic age in senescent cells within less than a week – these chemicals were tested against both Parkinson’s disease patients as well as healthy young skin cells; all proved successful.
Many diseases arise when genes stop functioning correctly or mutate, and gene therapy offers one solution by replacing or reversing bad genes or mutations. There are two primary forms of gene therapy: addition and silencing. With addition, new copies of an applicable gene are added directly into cells so they produce correct proteins, while silencing will stop an expression of any harmful ones that produce proteins that could potentially harm our body’s defenses.
Another technique involves using a virus to deliver a replacement gene directly into cells and avoid immune-system detection. While this approach remains experimental, early trials have yielded promising results: in six choroideremia patients treated with an AAV with REP1 genes showed improved vision over a six- to two-year period.
Researchers have developed gene-editing tools that allow them to directly alter DNA. Unfortunately, this complex process is both costly and time-consuming, so researchers are exploring alternative approaches such as using adeno-associated viruses to carry CRISPR into cells in order to speed up and decrease costs of gene editing. Once gene editing proves safe and effective it could have many uses including reversing aging processes as well as treating diseases like Alzheimer’s and cancer.
Cellular Rejuvenation
Reprogramming cells to restore their youthful function and prevent degenerative diseases is a promising area of research. Techniques like epigenetic reprogramming, senolytic interventions, mitochondrial restoration, stem cell-based approaches and CRISPR have shown substantial promise in preclinical models and several are being explored cautiously as early-stage clinical trials. But transitioning cellular rejuvenation from experimental success into real world practice requires innovative strategies for safety, delivery precision, personalized treatment planning, ethical oversight oversight and affordability – which may require new approaches compared with experimental successes seen so far in research labs and preclinical models.
Researchers had long believed that changes to DNA were the primary contributors to aging; however, recent discoveries indicate otherwise. Epigenetic changes affect how genes are expressed, rather than genetic sequence itself and thus play an integral part in influencing aging processes. They can even be affected by factors outside cells.
Immunologist Katja Simon has discovered ways to increase autophagy efficiency, thus slowing the aging of immune cells and thus delaying their decline.
Environment has an enormous effect on how quickly our cells age. A growing body of evidence points to lifestyle factors — like diet, exercise and stress management — being key players.
Research team behind Yamanaka factors have discovered that their cocktail of reprogramming factors can rapidly erase an older cell’s identity and restore its chromatin structures back to their younger state, an essential step in understanding cellular rejuvenation. Unfortunately, however, its long-term effectiveness remains uncertain and future studies must determine if cells revert back into senescent states after removal of cocktails from circulation.
Cellular rejuvenation offers us hope of revolutionizing healthcare and lengthening healthy lifespans, yet realizing this vision requires multidisciplinary cooperation, advanced biomarkers, personalized treatments tailored specifically to each patient, transparent regulatory frameworks and scaleable production – ingredients which together could take this promise from experimental success to clinical practice and change how we live our lives forever.
Chemical Rejuvenation
Harvard Medical School researchers have made an unprecedented breakthrough by uncovering a chemical way to rejuvenate cells and return them to a youthful state, potentially providing an easier, cheaper and faster alternative to gene therapy. Their research, published in Cell journal, focused on epigenetics – studying how changes to how genes “on/off” control an organism’s aging without altering DNA sequence itself.
Chemical epigenetic reprogramming was utilized by researchers to restore cells back to their stem cell state, by creating temporary but fast-healing cuts in mice’s DNA and artificially inducing epigenetic modifications, known as CERs, that changed how certain genes were expressed in cells of aged animals. When CERs affected which genes were expressed more or less actively than usual, the mice appeared younger; suggesting reversing changes can reverse aging even among mature creatures.
Sinclair’s lab developed a tool to confirm their discovery; using it they found OSK treatment significantly lowered both biomarkers and estimated biological age – suggesting the cocktail had reversed cellular senescence.
Researchers then tested six chemical combinations to find one that could fully reverse senescent cell reprogramming. All six cocktails successfully decreased both their estimated chronological age and genome-wide transcript profiles to return them back to youth; among these six cocktails was C1 which reversed key transcriptional signatures associated with senescence within 7 days!
Importantly, rejuvenation was achieved without pushing cells into stem cell state – something which can lead to excessive cell growth and proliferation, leading to cancer. Instead, Sinclair envisions a future in which age-related diseases could be effectively treated while injuries healed more efficiently; making their dream of whole-body rejuvenation come true. “This new discovery offers the possibility of reverse aging with just a pill and its applications range from improving eyesight improvement to treating various age-related diseases,” Sinclair explained in a statement.
