Scientists have successfully reversed aging in mice by rejuvenating old cells in muscles, tissues and organs. They claim this advance brings them one step closer to developing anti-ageing therapies that will restore health and extend lifespan.
Scientists accelerated DNA breaks in mice’s epigenome, altering how their genes function without changing their sequence. Epigenetic factors temporarily stopped their normal work of regulating genes and instead moved toward breaks to coordinate repairs.
Reversing aging in the eye
Harvard researchers recently reported the success of their experiment reprogramming complex tissues such as the eye to an earlier age, opening up possibilities for clinical trials that may help rejuvenate human bodies.
Scientists injected three youth-restoration genes-Oct4, Sox2, and Klf4–into the retinas of aging mice to reset the eye. They watched as cells rejuvenated themselves. Furthermore, the team administered this treatment in mice with damaged optic nerves in order to see if vision restoration could take place; retinal ganglion cells (neuron connections that connect optic nerve to rest of eye) reversed aging process while recovering their senses for light and motion perception.
Scientists were able to induce the epigenetic changes they desired through an experimental technique developed in their lab. They increased DNA breaks while making sure most fell outside coding sections that can trigger mutations, using what’s known as inducible changes to epigenome, or ICE system. Breaks temporarily stopped epigenetic factors from performing their normal job of gene regulation before changing how DNA folded itself back together again.
This manipulation reversed aging in both eyes and organs of ICE mice, as well as other tissues. Researchers are studying their epigenetic patterns in order to better understand why age reversal occurred, as well as applying their TEMPO technique and clock to other bodily fluids such as liver bile and joint fluid to develop drugs that target specific cells driving disease and aging.
Scientists have long attempted to combat aging by targeting specific cells that have lost the ability to regenerate or function normally. A Harvard study opens the way for rejuvenation therapies that target not only damaged but healthy cells as well, according to Munoz Canoves (61), who last year unveiled mechanisms that enable muscle regeneration while turning her Spanish laboratory into Altos Labs dedicated to rejuvenation research. Unfortunately, even if their approach proves safe and effective on humans it will take decades before any anti-ageing drug can be developed that can be approved clinical use by FDA approval for clinical use by FDA approval for clinical use by regulators.
Reversing aging in the brain
Scientists at Harvard medical school laboratories have achieved a breakthrough that may ultimately lead to whole-body rejuvenation: turning old mice with weak and feeble muscles into healthy animals by rejuvenating their muscles, tissues and organs. The discovery has opened new avenues for treating age-related diseases and injuries and may one day even help extend human livespan.
Studies using genetically engineered mice devoid of an enzyme to protect telomeres against shortening and reverse the signs of aging have yielded surprising results: scientists discovered that injecting them with protein PF4 reversed cognitive aging due to decreased immune response which reduced inflammation in the brain, thus improving cognition. Additionally, injections caused the body to produce more natural PF4, further reversing brain aging.
Researchers who developed this technique utilized a tool designed to detect epigenetic changes in cells. They increased the rate of DNA breaks to simulate fast-forward aging while making sure most were outside coding regions, which prevented genes from being altered but caused them to stop working as intended in terms of protein regulation and rearrange chromosome folding, leading to something known as epigenetic noise where information in DNA becomes scrambled or lost over time.
To investigate whether epigenetic degradation could be reversed, researchers administered AAVs containing Yamanaka factors that reprogram adult cells back into versatile stem cells. When they looked for signs of aging in muscles, skin, and organs of these mice treated with this AAV cocktail they observed much younger-looking counterparts than untreated control mice with many biomarkers completely reversed!
To further corroborate their findings, the team examined methylation patterns in the DNA of mice treated with Yamanaka cocktails and observed a change in some areas where methylation had reversed to appear as though it had been transcribed again – suggesting they can reset a genome’s epigenetic state by turning back time and reverse aging effects.
Reversing aging in the heart
Cedars-Sinai researchers recently conducted a study, published this week in the European Heart Journal, that shows how injections of cardiac progenitor cells may someday help older hearts act like younger ones. To do this, middle-aged mice were given injections derived from human heart stem cells in order to reverse signs of aging such as damaged arteries and decreased cardiac function.
To do this, they briefly activated four genes that can transform adult cells into embryonic-like pluripotent stem cells that can then differentiate into any cell in the body, including cardiac muscle. Pluripotent stem cells have the power to restore organ health – so researchers were delighted by their results!
The team selected three of the four Yamanaka factors and inserted them into viruses to safely infiltrate cells. After injecting this combination into an aged mouse’s eye, its cells began regenerating healthy retinal ganglion cells at the back of its eye and also produced new axons connecting each of the cells back together and to neurons in its brain.
However, scientists weren’t finished yet: They then used cells injected into an animal heart with damaged blood vessels and arteries to test if they could stop scar tissue formation that causes narrowing of arteries and blockage of blood flow. Their experiments found that injecting cells reduced scarring significantly while simultaneously increasing circulation throughout the heart.
As their hearts recovered their strength and ability to pump blood efficiently again, treated mice showed increased telomere lengthening as their hearts recovered strength and began pumping blood again. This finding is exciting because our telomeres shorten as we age; thus speeding up the aging process.
Belmonte and his colleagues plan to apply the same approach to other organs, including kidneys and pancreas, while simultaneously rejuvenating an animal suffering from Hutchinson-Gilford progeria syndrome and rapidly aging genes, by administering injections with mutant anti-aging genes that could extend its life by 30 percent.
Reversing aging in the lungs
Researchers have developed an effective strategy to reverse aging in mice lungs, suggesting this might be one organ where such reverse can take place. Led by Harvard Medical School scientists and published in Cell, this study builds upon previous work which shows how an imbalance between gene activity and information systems controls can cause animals to age independently of changes to DNA itself – this process is known as epigenetic aging; thus reversing this process may restore health and vitality among aged mice.
To test their theory, scientists implemented temporary, fast-healing cuts in the DNA of young and aged mice. They made sure the cuts didn’t interfere with DNA coding and that most breaks occurred near areas with epigenetic marks – these marks don’t alter gene sequence but regulate whether genes are turned “on” or “off.”
Mice with their epigenetic patterns altered by DNA cuts began to look and act older, while increasing levels of biomarkers for aging. When scientists gave these animals gene therapy that reversed these epigenetic changes, however, their animals looked and behaved younger again.
No details have yet been given on how epigenetic reprogramming was accomplished, although experts not involved with the study dispute any suggestions of age reversal. As this work employed dramatic DNA breaks that may have other side-effects and may not be viable solutions for producing cells with youthful epigenetic patterns, but researchers hope their work may pave way for new approaches for extending lifespan and rejuvenating youthful physiology.
These findings support Sinclair and his team’s hypothesis that mammalian cells maintain a backup version of the epigenetic software program they use to switch genes on and off, and can regain it when necessary. Sinclair calls this system ICE (for inducible changes to the epigenome). During an experiment using this ICE system, epigenetic factors responsible for gene regulation were temporarily suspended and brought directly to sites of DNA damage in order to coordinate repair; once healed they returned back into their original spots.