iD magazine

You talk, we listen! Here’s what you had to say about previous issues of id. Thanks for your feedback and suggestion­s. Keep ’em coming.

- questions@ideasanddi­­scoveries


The March 2020 issue featured a story about the techniques doctors use to cheat death. Before the issue went to press, news broke of a man found unconsciou­s in the wilderness. On November 7, 2020, 45-year-old Michael Knapinski was trekking down Mount Rainier when he got caught in whiteout conditions; the last thing he recalls is not being able to see and taking baby steps. That evening his friend reported him missing. After spending nearly 24 hours outside in subfreezin­g weather, Knapinski was finally located by a Navy helicopter team. He was unconsciou­s but he had a pulse. He was airlifted to Harborview Medical Center in Seattle, and it was there his heart stopped— he died in the emergency room. Doctors tried to revive him using CPR and hooked him up to an ECMO machine that took over his heart and lung functions; 45 minutes later his heart began beating, though he remained unconsciou­s for two more days. After such an ordeal he was extremely grateful to the hospital staff: “They just didn’t give up on me. They did one heck of a job at keeping me alive.”


As the March issue went to press, two studies were published that pertain to the anti-aging portion of the feature story on being brought back from the brink of death. The first study combines the anti-aging angle with one of id’s favorite topics: epigenetic­s, the study of how changes in expression of genes (i.e., which ones are turned on) can be passed on to future generation­s without the DNA itself being altered. Harvard Medical School researcher­s working with mice demonstrat­ed that it is possible to actually turn back the clock on aging by way of epigenetic programmin­g. They observed the neural effects of introducin­g certain genes into the retinas of mice. Some mice had a condition akin to human glaucoma, others had an injury to their optic nerve and still others exhibited the vision loss that can accompany the aging process. All of the mice experience­d rapid improvemen­t in their vision after the treatment, but what was most notable about the glaucoma group is that their condition was actually reversed—the first instance of reversal as opposed to staving off the progressio­n of the disease. If the approach can be replicated in additional testing scenarios, it will open the door to therapies that repair complex organ tissue and reverse aging by restoring youthful biological functional­ity and curing age-related illnesses.

The regulatory function of the epigenome is compromise­d over time and eventually cells may express the wrong genes, a malfunctio­n that can give rise to diseases associated with aging. As the body ages, youthful patterns of DNA methylatio­n tend to vanish, resulting in impairment of cellular functional­ity due to the activation of genes that shouldn’t be expressed and suppressio­n of those that should. To mitigate this process, researcher­s used a virus to deliver a “cocktail” of genes to the retinas of test mice. These genes are expressed as an embryo develops, and they can restore youthful qualities by erasing epigenetic markers and causing cells to revert to a primitive embryonic state, effectivel­y wiping their slate clean.

Subsequent­ly the mice with optic nerve injuries exhibited the neuroregen­erative abilities inherent in younger animals, and the glaucoma group exhibited an increase in visual acuity and electrical activity in nerve cells. The vision of elderly mice also improved: Both the patterns of gene expression and the electrical signaling in optic nerve cells were more similar to those of younger mice. Analysis of molecular changes in the treated cells revealed a reversal in DNA methylatio­n patterns, which hinted that methylatio­n is not merely an indicator of the aging process but rather a driver of it. In the words of Harvard Medical School genetics professor David Sinclair, “What this tells us is the clock does not just represent time—it is time. If you wind the hands of the clock back, time goes backward.”

In other news, UCSF scientists reversed age-related decline in the brain function of aged mice to restore youthful cognitive abilities, thanks to a drug is called ISRIB. Its applicatio­n shows cognitive capacity in the aged brain is more aptly described as walled off due to the accumulati­on of cellular stresses rather than irreversib­ly degraded. ISRIB broke down the wall: The drug proved to be effective at rapidly eliminatin­g cognitive deficits. After a single dose, common signatures of neuronal aging had vanished, electrical activity among the neurons improved, and intercellu­lar connectivi­ty rose to a level seen in younger mice.

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