genetic transcription (premium)

This field explores the idea of genetic transcription and its role in aging while incorporating Dr. David Sinclair (outlined below) work into a field that utilizes the same process explained below to rejuvenate our cells. “Loss of Epigenetic Information Can Drive Aging, Restoration Can Reverse It. Study in mice implicates changes to way DNA is organized, regulated rather than changes to genetic code itself”

From a recent article in Time Magazine. “It’s been 13 years in the making, but Dr. David Sinclair and his colleagues have finally answered the question of what drives aging. In a study published Jan. 12 in Cell, Sinclair, a professor of genetics and co-director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School, describes a groundbreaking aging clock that can speed up or reverse the aging of cells.

Scientists studying aging have debated what drives the process of senescence in cells—and primarily focused on mutations in DNA that can, over time, mess up a cell’s normal operations and trigger the process of cell death. But that theory wasn’t supported by the fact that older people’s cells often were not riddled with mutations, and that animals or people harboring a higher burden of mutated cells don’t seem to age prematurely.

Sinclair therefore focused on another part of the genome, called the epigenome. Since all cells have the same DNA blueprint, the epigenome is what makes skin cells turn into skin cells and brain cells into brain cells. It does this by providing different instructions to different cells for which genes to turn on, and which to keep silent. Epigenetics is similar to the instructions dressmakers rely on from patterns to create shirts, pants, or jackets. The starting fabric is the same, but the pattern determines what shape and function the final article of clothing takes. With cells, the epigenetic instructions lead to cells with different physical structures and functions in a process called differentiation.

In the Cell paper, Sinclair and his team report that not only can they age mice on an accelerated timeline, but they can also reverse the effects of that aging and restore some of the biological signs of youthfulness to the animals. That reversibility makes a strong case for the fact that the main drivers of aging aren’t mutations to the DNA, but miscues in the epigenetic instructions that somehow go awry. Sinclair has long proposed that aging is the result of losing critical instructions that cells need to continue functioning, in what he calls the Information Theory of Aging. “Underlying aging is information that is lost in cells, not just the accumulation of damage,” he says. “That’s a paradigm shift in how to think about aging. “

His latest results seem to support that theory. It’s similar to the way software programs operate off hardware, but sometimes become corrupt and need a reboot, says Sinclair. “If the cause of aging was because a cell became full of mutations, then age reversal would not be possible,” he says. “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. (Outside of the lab, epigenetic changes can be driven by a number of things, including smoking, exposure to pollution and chemicals.) 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—in the case of the mice, the instructions guided the cells to restart the epigenetic changes that defined their identity as, for example, kidney and skin cells, two cell types that are prone to the effects of aging. 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.

“We’re not making stem cells, but turning back the clock so they can regain their identity,” says Sinclair. “I’ve been really surprised by how universally it works. We haven’t found a cell type yet that we can’t age forward and backward.”

Of course this field aims to reverse the aging process.

Genetic transcription, the process by which DNA is converted into RNA, can play a role in aging through a variety of mechanisms. Here are a few examples:

Telomere shortening: As cells divide, the telomeres at the end of their chromosomes get shorter. This shortening can eventually lead to cellular senescence, which is when cells stop dividing and functioning properly. Telomere shortening is influenced by genetic transcription, and certain factors, such as stress and inflammation, can accelerate this process.

DNA damage and repair: DNA damage can accumulate over time and lead to cellular dysfunction and aging. Genetic transcription is involved in both causing and repairing DNA damage. For example, mutations in genes involved in DNA repair can lead to premature aging syndromes, and increased expression of certain DNA repair genes can extend lifespan in animal models.

Epigenetic changes: Epigenetic changes, such as DNA methylation and histone modifications, can alter gene expression without changing the underlying DNA sequence. These changes can be influenced by environmental factors and can affect aging-related processes such as inflammation and cellular senescence.

I know there are other fields regarding this area of interest. One is not necessarily better than the other. They are different approaches. Different perspectives. Different ways to go about the same goal. Like the saying there is more than one way to skin a cat, terrible as that may be. Rather than getting overwhelmed by the available options consider them to be like a menu, and you can try a different dish each day and never get bored.

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