Long Life and Health
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Can Genes be Modified to Reverse Aging and Extend the Human Lifespan?

The answer to radically extending the human lifespan may already be buried deep with our genes.

Researchers into antiaging technologies and potential life-extending therapies have lately focused their attention on the concept of senescence. Every cell in your body has a lifecycle and a lifespan, all of its own. New, young cells are strong, and they renew themselves through cellular division. But, every cell eventually reaches a point when it can no longer divide, and it goes into a kind of hibernation called senescence – a state of permanent growth arrest.

An interesting approach to life extension has been a deep dive into figuring out which genes specially program our cells to become senescent. Theoretically, if we could do that through gene modification, we could stop or even reverse the process. 

Recently, researchers from the Institute of Zoology of the Chinese Academy of Sciences (CAS), Peking University, and Beijing Institute of Genomics of CAS have collaborated to identify new human senescence-promoting genes by using a genome-wide CRISPR/Cas9 screening system and provide a new therapeutic approach for treating aging and age-related diseases.

The scientists identified more than 100 candidate senescence-promoting genes, but the most intriguing and promising among them was a gene called KAT 7.

KAT7 belongs to a diverse group of enzymes known as histone acetyltransferases, cellular components that are evolutionarily conserved from yeasts to humans. These proteins are known to play central roles in chromatin remodeling and act as transcriptional regulators to control gene expression. The researchers found that switching off KAT7 triggered a cascade of molecular events that alleviated cellular senescence –resulting in cells staying younger for longer.

Taking this find a dramatic step further, the Chinese team developed an experimental gene therapy that used involved the delivery of a CRISPR-based therapeutic. CRISPR is a powerful “gene editing” tool, meaning it allows researchers to easily alter DNA sequences and modify gene function.

The gene editor was designed to inactivate KAT7 in vivo, working specifically in liver cells. The researchers administered the treatment intravenously to both normal aged mice and a cohort of genetically modified animals that act as a model of accelerated aging.

The results were striking. After around half a year, the treated mice showed a reduction in aging markers, more grip strength, and lived 25 percent longer than the untreated controls.

Promisingly, no toxicity or observable side effects were noted in the animals that received the KAT7 gene therapy. Still, many other questions need to be answered before the KAT7 gene therapy is ready for clinical primetime or eventual use in humans.

Among these is the unknown of whether extinguishing KAT7 activity may prompt unwanted effects in other critical genes. This risk is particularly concerning given the history of CRISPR therapeutics mistakenly editing off-target genes – with some devastating consequences.

Still, this is a very promising path that could eventually lead antiaging researchers to that proverbial fountain of youth.

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