#epigentic entropy

[a-typical]

Scientists Have Reached a Key Milestone in Learning How to Reverse Aging

Loss of epigenetic information as a cause of mammalian aging

Scientists Have Reached a Key Milestone in Learning How to Reverse Aging

Highlights from the Study

Cellular responses to double-stranded DNA breaks erode the epigenetic landscape

This loss of epigenetic information accelerates the hallmarks of aging

These changes are reversible by epigenetic reprogramming

By manipulating the epigenome, aging can be driven forward and backward

“Underlying aging is information that is lost in cells, not just the accumulation of damage,” says Dr. David Sinclair, a professor of genetics and co-director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School. His latest results seem to support that theory.

All living things experience entropy manifested as a loss of genetic and epigenetic information. Genetic information is the hardware and the epigenome is the software. We think aging is due to corrupted software, that can be rebooted to restore youth.

It’s similar to the way software programs operate off hardware, but sometimes become corrupt and need a reboot. But by showing that we can reverse the aging process, that shows that the system is intact, that there is a backup copy and the software needs to be rebooted.”

In the mice, he and his team developed a way to reboot cells to restart the backup copy of epigenetic instructions, essentially erasing the corrupted signals that put the cells on the path toward aging. They mimicked the effects of aging on the epigenome by introducing breaks in the DNA of young mice. - Once “aged” in this way, within a matter of weeks Sinclair saw that the mice began to show signs of older age—including grey fur, lower body weight despite unaltered diet, reduced activity, and increased frailty.

The rebooting came in the form of a gene therapy involving three genes that instruct cells to reprogram themselves— These genes came from the suite of so-called Yamanaka stem cells factors—a set of four genes that Nobel scientist Shinya Yamanaka in 2006 discovered can turn back the clock on adult cells to their embryonic, stem cell state so they can start their development, or differentiation process, all over again. Sinclair didn’t want to completely erase the cells’ epigenetic history, just reboot it enough to reset the epigenetic instructions. Using three of the four factors turned back the clock about 57%, enough to make the mice youthful again.

Using a system called “ICE” (Inducible Changes to the Epigenome), we show the act of repairing DNA breaks accelerates aging at the physiological, cognitive, & molecular levels, including erosion of the epigenetic landscape, loss of cell identity, senescence & increased epi-age ... "We show these changes can be reversed by OSK-mediated rejuvenation. With an ability to drive aging in both the forward and reverse directions, we conclude that loss of epigenetic information is a cause of aging in mammals."

“We haven’t found a cell type yet that we can’t age forward and backward.”

In 2020, Sinclair reported that in mice, the process restored vision in older animals; the current results show that the system can apply to not just one tissue or organ, but the entire animal. He anticipates eye diseases will be the first condition used to test this aging reversal in people, since the gene therapy can be injected directly into the eye area.

"If correct, it means that cancer, diabetes and Alzheimer's might have the same underlying cause that can be reversed to treat or cure age-related conditions with a single treatment. Experiments in the lab are testing this."

Even before that happens, the process could be an important new tool for researchers studying these diseases.

"The age-reversal technology -- virally-delivered genes (Oct4, Sox2, Klf4, aka, Yamanaka factors), which turn on an embryonic program -- is being tested at @lifebiosciences in non-human primates. Results out in a few months from Bruce Ksander's lab & http://lifebiosciences.com"

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