Scientists have made a truly groundbreaking discovery that may reduce or reverse brain aging. The “fountain of youth” lies within our bodies themselves rather than within some mythical stone or pill.
Shinya Yamanaka earned the prestigious Nobel Prize for discovering a combination of four proteins that transform adult cells back into embryonic-like stem cells, rejuvenating eyes and muscles in mice as well as prolonging their lives. He used these to extend their lifespan.
1. Using Yamanaka Factors to Reverse Cell Aging
Shinya Yamanaka won a Nobel Prize for discovering a combination of proteins that reprogram adult cells to become stem cells capable of developing into any cell type – revolutionizing aging research. But following in his footsteps has spurred further developments; scientists believe they can even reverse aging within whole organisms like humans.
The Yamanaka factors are four transcription factors that activate or repress genes when they’re needed, creating an opportunity to use these factors to transform fibroblasts lining our internal bodies into induced pluripotent stem cells (iPSCs) for transplant or rejuvenation purposes. Once created, these iPSCs exhibit many of the characteristics found in young cells such as longer telomeres and reduced oxidative stress that’s one of the major causes of aging.
Yamanaka conducted his original study by reprogramming cells in the lab so they would shed their identity as skin cells and become iPSCs, and applying these reprogrammed cells directly onto mice skin where they began producing new cells at an astounding rate, thus reversing effects associated with aging such as declining eyesight and shorter attention span.
But Yamanaka’s method was intended for lab settings; applying his methods on living animals has proved more challenging. Reverting cells back to an embryonic state could result in their overgrow and cancerous proliferation; instead, researchers explored another approach, showing in 2016 how adding small amounts of Yamanaka factors as short pulses may improve human cell functionality.
To reduce cancer risk, the team selected Oct3/4, Sox2, and Klf4 (known collectively as OSKM) because these proteins have reduced ability to induce cancer. When tested on healthy mice, OSKM demonstrated significant muscle growth benefits as well as improving eye nerve functions while even reversing age-related vision loss in some. Based on these promising findings, OSKM was then attempted on sick mice with promising results.
2. Using DNA Breaks to Reverse Cell Aging
Scientists have long attempted to slow or even reverse cell aging to extend human lifespan, using methods ranging from genetic engineering and gene therapy. Though their efforts are encouraging, experts caution that an effective rejuvenation method remains decades away; in the meantime we’ll need to rely on other ways of improving our quality of life.
Scientists had long sought to activate autophagy – the process by which cells recycle old and damaged parts – as a means to extend lifespan in mice and humans alike. But a recent study suggests this wasn’t necessary: instead, simply decreasing fat build-up could improve health and extend lifespan by itself.
Researchers achieved this by inducing DNA breaks to mice’s cells, without harming the gene code itself. Such DNA modifications don’t alter any coding sections and act similarly to damage from pollution and sunlight which leads to cells ageing prematurely. The inducible epigenetic changes (ICE) method works by producing rapid self-healing cuts in DNA that regulate how genes are expressed – an approach much safer than risky gene therapies which can cause mutations.
After injecting their aging mice with a DNA-altering cocktail, the team found that DNA breaks reversed many markers associated with cellular aging – they looked younger and behaved younger again! Furthermore, it prevented cancer and other diseases as well as improved kidneys, muscles, skin, and eyes of these mice.
Importantly, researchers only managed to reverse mice’s cell aging–not their overall biological age. If we could find an effective and comprehensive way of rejuvenating cells we could effectively reset our biological clocks; researchers are currently exploring this possibility using genetic and chemical approaches in human cells; understanding which resistant cells need further attention can speed the creation of new techniques for resetting biological ages.
3. Using Epigenetics to Reverse Cell Aging
Epigenetics acts like software on our cells, with DNA acting as the hardware and proteins and chemicals called epigenetics as its software. Epigenetics consists of proteins and chemicals that sit atop genes like freckles on a face to tell them “what to do and when.” Unfortunately this process can be compromised by environmental toxins, smoking cigarettes, aging as well as unhealthy habits such as an unbalanced diet or lack of sleep causing irreparable damage to tissues and organs over time.
Researchers discovered that altering cell epigenetics could reverse mouse aging. To do this, they created a cocktail of Yamanaka factors and injected it into mouse retinal ganglion cells, the light-sensitive layer of eye’s optic nerve. This caused them to reprogram into embryonic stem cells reprogramming them back into biologically younger versions that looked and acted younger; additionally it promoted retinal injury recovery among aged mice. Their results were published in April 2023.
Wolf Reik, a molecular biologist at Altos Cambridge Institute of Science (a rejuvenation-oriented lab whose doors opened last year by rejuvenation specialist Altos Labs), and member of Babraham Institute’s scientific board wanted to determine whether this process could also work on other cells. Scientists induced drastic DNA breaks in mice cells to mimic damage caused by daily exposure to chemicals, sunlight and other factors which contribute to aging. Their approach was known as inducible changes to epigenome (ICE). Ice-induced DNA breaks did not alter the coding portions of mice’s genes, which would otherwise trigger mutations, but they did alter how DNA folds, prompting epigenetic factors to temporarily stop their normal work and move directly toward DNA breaks to coordinate repairs before returning back to their regular duties.
Scientists were able to reset the epigenetics of other cell types, including muscle, kidney and retinal cells – effectively giving these mice younger, healthier appearances and improving their ability to regenerate tissues and organs. If successful, their experiments could one day lead to medicines designed to slow or even reverse human aging processes.
4. Using Rapamycin to Reverse Cell Aging
Rapamycin, an mTOR inhibitor typically used to prevent organ transplant rejection, has been found to extend longevity in laboratory animals while delaying age-related diseases such as inflammation. As opposed to lifestyle changes, anti-ageing drugs can reach your body before disease-causing processes like oxidative stress or inflammation take hold in your body; one such drug that could simultaneously prevent multiple diseases while increasing lifespan would truly be revolutionary.
Anti-ageing remedies have been tried out countless times and most have proven unsuccessful for various reasons, from being ineffective due to working through unproven mechanisms to producing undesirable side effects that are too severe or unwanted for daily use. By contrast, mTOR inhibitors like rapamycin and everolimus are clinically approved medications with well-tolerated side effects known for years and no serious risks involved.
Although mTOR inhibition is generally associated with slower growth, it has also been found to extend life in several species – humans, flies and yeast alike. Geroconversion is thought to be responsible for this lifespan extension: this twisted growth phenomenon leads to hypertrophic and hyperfunctional cells developing (like cancerous ones) while simultaneously slowing cell division rates.
Rapamycin treatment of mice significantly extends maximum lifespan while slowing the onset of age-related diseases in flies and yeast.
At present, it remains uncertain whether rapamycin and other mTOR inhibitors will be effective at reversing all of the overt diseases of aging, or just some. But recent research indicates that short-term exposure to rapamycin had similar positive results as long-term use – this bodes well as it indicates that combinations of mTOR inhibitors with other therapies could extend human lifespan and healthspan without needing lifelong medication treatment.
