Harvard scientists have devised an ingenious way of turning back time with mice by manipulating epigenetics – chemical changes which influence gene activity without altering DNA sequence. By manipulating epigenetics, Harvard scientists were able to make their mice healthier by making changes through epigenetics which affect gene activity without altering DNA sequence.
These scientists have also discovered six chemical cocktails that can revitalize cells quickly in under a week without altering cellular identity, suggesting that old cells contain information to reset their biological age.
Identifying the Fountain of Youth
Since antiquity, explorers and adventurers have sought the Fountain of Youth: a mythical spring that bestows eternal youth upon its drinkers. Ponce de Leon famously made his journey across Florida in pursuit of immortality via this search for the Fountain of Youth in 16th century Florida; today’s scientists use pipettes rather than compasses when exploring cells; but their quest remains strong!
Scientists’ search for the Fountain of Youth has inspired scientists to experiment with ways of rejuvenating and prolonging life, from genetically reprogramming cells to creating artificial fountains of youth that make people appear younger. But Harvard scientists recently made headlines when they reversed aging in mice using chemical means – published in Cell on July 12 2023 as evidence. Their results prove it is possible to turn back time on cells’ pathways toward aging by switching off certain DNA signals that cause them to age prematurely.
Researchers conducted their study by injecting an inbred mouse with the Yamanaka gene, which is responsible for reprogramming its genetic instructions to stop uncontrolled growth and ageing. After injecting their chosen strain with Yamanaka gene, scientists then administered chemicals that “rebooted” cells by restoring young gene expression – these mice experienced many health benefits including improved eyesight and longer lifespans.
To further test their theory, researchers conducted an experiment known as heterochronic parabiosis. In this procedure, a surgeon slits two anesthetized mice down their flanks before suturing and stapleing them together alongside each other side by side – because these mice were inbred, their immune systems don’t attack each other resulting in twin clones that share both genes and cellular clocks.
Reversing aging in these mice indicates that a similar approach might work on humans as well, and researchers are currently planning clinical trials with human participants to test this theory. If successful, this technique could become an exciting advancement in regenerative medicine allowing doctors to repair damaged tissues more efficiently while possibly lengthening life spans of their patients.
Reversing Cellular Aging
Scientists once held that DNA changes were at the root of all aging; however, Harvard Medical School researchers have recently demonstrated that degradations in gene organization and regulation may also contribute to this phenomenon, independent from changes to DNA itself. Their research paper published in Cell shows how reverse this degradation can reverse cell aging.
The team examined cells from three donors aged 22 years, 94 years old, and one with progeria, an inherited disorder causing premature aging. Reversing PTEN gene decline reversed cell aging leading to loss of function in cells.
This approach could pave the way to innovative treatments for human diseases and move us one step closer to finding our fountain of youth. Now scientists are working hard to bring their findings into clinical testing environments where they can determine their effects on both individual cells and whole organisms.
In their most recent research study, the team identified six chemical cocktails that, within seven days and without harming cellular identity, restored youthful genome-wide transcript profiles and reversed transcriptomic age. These cocktails included CHIR99021 which blocks glycogen formation activated during sleep to store energy; tranylcypromine as an antidepressant; and valproic acid, commonly prescribed to treat bipolar disorder.
Scientists analyzed cells using sophisticated assays that distinguish young and old cells based on their ability to replicate. Next, they introduced chemicals into both young and old cells and observed what effect they had. Their results were amazing: in addition to reversing visual signs of aging, the cocktail of chemicals rejuvenated cells by prompting faster cell division rates as well as improving regeneration capabilities.
Kyoto University scientist Shinya Yamanaka made history when he demonstrated how specific transcription factors could transform adult cells into induced pluripotent stem cells (iPSCs). Although iPSCs can become any cell in the body – including muscle and brain cells – fears regarding potential for cancerous growth has limited clinical use of this approach; the research team’s work circumvents this issue by reprogramming cells using chemicals rather than Yamanaka’s process, thus potentially decreasing risks for cancer.
Identifying the Causes of Aging
One of the major causes of aging is cell mutation. Over time, these mutations prevent cells from functioning correctly and lead to tissue and organ breakdown – leading to disease and ultimately death. Scientists have identified numerous processes which cause this damage – known as hallmarks of aging.
Scientists have long assumed that DNA changes are the main driver of aging. But recent research indicates there may be other causes as well, including other factors which affect gene activity without changing genetic code – something known as epigenetics; or environmental stressors hastening aging processes.
Researchers have long sought a way to reverse the effects of aging. Their efforts include studying gene regulation mechanisms, pinpointing causes for aging and devising treatments. Scientists believe that reverse cellular aging could extend health span and decrease risks of disease.
Scientists have recently discovered that scientists have discovered how the signs of aging can be reversed using chemicals to slow or reverse several biological processes, thus increasing longevity significantly and particularly benefiting those at high risk of age-related diseases. This research is especially promising for people at greater risk.
Researchers have also found that making simple lifestyle adjustments can slow the rate of aging in a person. Six women between 46 and 65 who took part in an eight-week program consisting of diet changes, exercise, relaxation exercises and nutritional guidance experienced a decrease in their biological ages; on average participants saw an overall reduction of 4.6 years. Researchers noted that participants weren’t under any significant stress at the time of study, which is important because previous research has demonstrated that prolonged stress can actually accelerate biological aging by activating stress responses such as chronic depression or anxiety.
Reversing Aging in Mice
Scientists may be on the brink of discovering the mythical Fountain of Youth after rejuvenating worn out organs in aged mice. Their results offer hope to researchers working on expanding human lifespan and improving health as people age.
Scientists have recently demonstrated that aging can be reversed through cell reprogramming. Reactivating genes will allow cells to turn back on certain features that cause age-related damage and mistakes that lead to symptoms associated with aging.
Scientists have developed a system to induce epigenetic changes without altering genetic code itself. The system utilizes DNA breaks that do not modify genes directly but instead alter how they fold – similar to daily sunlight exposure, chemicals exposure or environmental factors causing DNA damage.
Sinclair and her team used ICE, a DNA breakage tool, to cause genetic changes in mice genomes. Most of the breaks weren’t located near any genes that would trigger mutations; rather they occurred mostly near areas that control whether certain genes are switched on. They also made sure that most breaks did not compromise cell identity so as to reactivate the epigenetic system in these mice.
When applied to mice that had already displayed signs of aging, the ICE system caused them to look younger and act healthier. Brain cells and testes began producing new cell divisions while fertility returned; additionally their intestines and spleens started functioning normally and vision improved dramatically.
Sinclair and her team injected some older-seeming mice with an AAV containing three Yamanaka factors known as OSK, to reverse vision loss in older animals. Mice that received AAVs also looked and behaved much younger with restored muscle and kidney functions.
Harvard researchers hope that, to further demonstrate that their work is successfully reversing aging, they plan to inject older mice with all six Yamanaka factors and observe what happens. Furthermore, human skin cells and senescent cells that accumulate as we get older will also be tested against this combination cocktail.
