Age Reversal Breakthrough: Harvard/MIT Discovery Could Enable ...

Scientists from Harvard Medical School, the University of Maine, and MIT have published a groundbreaking study revealing a chemical method to reprogram cells to a more youthful state. This technique offers a potential alternative to gene therapy for reversing aging. The implications of this research are vast, with potential applications in regenerative medicine, treatment of age-related diseases, and whole-body rejuvenation.
In a pioneering study, researchers from Harvard Medical School, University of Maine, and MIT have introduced a chemical method for reversing cellular aging. This revolutionary approach offers a potential alternative to gene therapy for age reversal. The findings could transform treatments for age-related diseases, enhance regenerative medicine, and potentially lead to whole-body rejuvenation.
Groundbreaking Discovery in Aging Reversal
In a monumental study, a team of researchers has revealed a novel approach to combating aging and age-related diseases. This work, undertaken by scientists at Harvard Medical School, introduces the first chemical method to rejuvenate cells, bringing them to a more youthful state. Prior to this, only powerful gene therapy could achieve this feat.
Mice in the Sinclair lab have been engineered to age rapidly to test the effectiveness of therapies to reverse the aging process. The mouse on the right has been aged to 150% that of its sibling on the left by disrupting its epigenome. Photo credit: D. Sinclair, Harvard Medical School. Credit: 2023 Yang et al.
Exploring the Methodology
This discovery builds on the finding that the expression of specific genes, known as Yamanaka factors, can transform adult cells into induced pluripotent stem cells (iPSCs). This breakthrough, which earned a Nobel Prize, prompted scientists to question if cellular aging could be reversed without pushing cells to become too young and potentially cancerous.
Rejuvenation and age reversal of senescent human skin cells by chemical means. Cells in the right two panels have restored compartmentalization of the red fluorescent protein in the nucleus, a marker of youth that was used to find the cocktails, before the scientists confirmed they were younger, based on how genes were expressed. Image credit: J. -H. Yang, Harvard Medical School. Credit: 2023 Yang et al.
In this recent study, the scientists probed for molecules that could, in tandem, revert cellular aging and refresh human cells. They designed advanced cell-based assays to differentiate between young and old, as well as senescent cells. The team employed transcription-based aging clocks and a real-time nucleocytoplasmic protein compartmentalization (NCC) assay. In a significant development, they identified six chemical combinations that could return NCC and genome-wide transcript profiles to youthful states, reversing transcriptomic age in less than a week.
Relevance and Potential Applications
The Harvard team has previously shown the possibility of reversing cellular aging without causing unregulated cell growth. This was done by inserting specific Yamanaka genes into cells using a viral vector. Studies on various tissues and organs like the optic nerve, brain, kidney, and muscle have yielded encouraging results, including improved vision and extended lifespan in mice. Additionally, recent reports have documented improved vision in monkeys.
These findings have profound implications, paving the way for regenerative medicine and potentially full-body rejuvenation. By establishing a chemical alternative to gene therapy for age reversal, this research could potentially transform the treatment of aging, injuries, and age-related diseases. The approach also suggests the possibility of lower development costs and shorter timelines. Following successful results in reversing blindness in monkeys in April 2023, plans for human clinical trials using the lab’s age reversal gene therapy are currently underway.
Views from the Research Team
“Until recently, the best we could do was slow aging. New discoveries suggest we can now reverse it,” said David A. Sinclair, A.O., Ph.D., Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School and lead scientist on the project. “This process has previously required gene therapy, limiting its widespread use.”
The team at Harvard envisions a future where age-related diseases can be effectively treated, injuries can be repaired more efficiently, and the dream of whole-body rejuvenation becomes a reality. “This new discovery offers the potential to reverse aging with a single pill, with applications ranging from improving eyesight to effectively treating numerous age-related diseases,” Sinclair said.
YEP. Promises! Promises! All the way back to the Egyptian Pharaohs and their “cost-intensive” bid for immortality. If one skips the fancy Jar and storage in a Mausoleum, it “more affordable”. It certainly won’t matter to the Dead. As such, memory and some photos will do.
If science is able to eliminate death control via senescence and apoptosis, and this technology spreads to everyone regardless of affordability, then birth control will become even more critical, in fact essential, to keep the human race from overpopulating into mass disaster. But it would also mean the end of natural human evolution, and the advent of taking our evolution into our own hands via genetic modification, because it would also mean the end of children, who are evolution’s natural mutation-testing petri dish, in the name of preserving terrestrial space for the survival of the glut of already living and henceforth virtually immortal adults.
1. Reversing methylation doesn’t cure aging. Even if we can control senescent cells, extend telomeres, restore healthy mitochondria, and restore the thymus gland. None of the aging scientists have a plan for repairing DNA errors. We incur 10,000 to 100,000 DNA breaks in each cell every day. 99%+ are repaired correctly, but some are not. Those mistakes carry over to future cell generations. Most DNA is junk, other genes are not important to the tissue damaged, so every mistake is not crucial. There are genetic variants that do a better job of repair and are more represented in the population of centenarians. And there are other things that accumulate like glucosepane, forms of amyloid plaques like misfolded transthyretin, genetically damaged mitochondria (they burn fuel inefficiently making wastes like lipofuscin which is the brown stuff in age spots, and these lipofuscin accumulations are not just on the skin. They are in muscle, heart, liver, kidneys, and the brain). We accumulate scar tissue. Accumulated latent infections often promote diseases, quite possibly schizophrenia, Alzheimer’s, and others. 2. The Earth can handle 500x current human population provided we develop technology to directly manufacture food from atoms, recycle everything, live in greater density, and in more diverse locations, like under domes in Antarctica, on the oceans, underground, on stilts above the surface of the land, without interfering with the land. And we can build large space stations and inhabit the Moon, Mars, asteroids… The Solar System can support many trillions of humans while dramatically improving the Earth environment. 3. Machines and tech that allow food surplus and some tech like contact lenses and braces, limit selection pressure, but it remains. We can and should reduce genetic birth defects through genetic surgery at the zygote or blastocyst stage. But there will always be natural births that are not repaired. We can fix some of this, but the repairs will be limited.
Were we playing God, when we developed fire? Clothing? Shoes? The plow? Antibiotics? Anesthesia? Eyeglasses? Scuba gear? Airplanes? Spaceships? If you haven’t noticed, life expectancy has tripled from the time of the Romans. If it doubles or triples again, how is that any different? I am not saying this treatment will double it. I would find that highly unlikely, but in combination with other advances, it is not inconceivable. It is very unlikely you will be kept alive, if you sign a do not resuscitate will, and have a copy in your wallet, or on a metal wristband. Certainly, no one will force you to take some elixir of life or anything like that. Seems exceedingly unlikely, anyway.
This would be extremely dangerous to try. It may be justified for some very important tissue like the retina to restore vision or the “hair” cells in the cochlea to restore stop maddening ear ringing, or to attempt to reverse spinal injuries. For whole body, there are many steps to go to insure safety. They have to test on normal mice, perhaps dogs, then monkeys, then people with some unusual condition where methylation aging is accelerated, then probably the very old, with little to lose. Probably with a very modest dose, at first. Probably a good 15 years, before they get to ordinary 40-70-year-olds. Maybe millionaires will get it in some Latin American country in 5 or 10 years. But that would be very risky. I would try gene therapy, way before I would try this.
There have been other successful attempts to correct fast aging mice. The type of fast aging mice are well-chosen, or engineered exactly for the test. Something of a parlor trick. But it has a purpose. It verifies what has gone wrong and that it can be fixed. But it gives the impression that you can just apply this to people with decent chance of success. Unless and until they dramatically increase the life expectancy of normal mice, they have not proven anything. That takes a few years. Hopefully, they already started a couple of years ago because doing something dramatic, like doubling average lifespan, will take 5 or 6 years to finish. There are many things which change during aging. This will not correct the other dozen, even if it worked perfectly in humans with no side effects. And that is a big “if” because it may restore senescent cells, which can be very dangerous. There is also the risk that cells will regress too far and forget what they are and create tumors. If you talk to aging scientists, they will likely emphasize the aspect of aging they are working on, and mostly ignore the others. Methylation may be upstream of some of these, but not all of them. Various types of accumulations with age are unlikely to be addressed. Things like the accumulation of genetic damage. Each cell’s DNA is broken 10,000-100,000 times a day. And most of the time correctly repaired, but not all the time. Errors are carried over to the next generation of cells. And there is this stuff called Glucosepane which accumulates between cells making the tissues stiff, especially arteries, and is implicated in a number of aging diseases. Neither our bodies nor scientists have figured out how to reverse this. There are also the accumulations of misfolded proteins called amyloid. And there are 30 kinds, not just the 1 involved in Alzheimer’s, like Wild-type ATTR Amyloidosis, which may be near certain over 110 years of age. That stiffens the heart, and make exertion very difficult.
How much reverse aging are we talking about? The paper as I understand it spoke of age reversal of only a few years. Also how long will this “pill” remain in effect? Will there be a rebound or is the effect permanent? Much remains to be done but still a groundbreaking paper even if the results don’t lead to an anti-aging pill.