The 'jumping genes', a new target to curb diseases associated with aging such as progeria

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An important part of our genome is capable of moving from one place to another on the chromosome.

Those

genes (transposons, for those in the know) may be a key to fighting diseases associated with premature aging, and perhaps also to improving health during normal aging.

This is demonstrated by a group of researchers headed by the Spanish scientist

who has managed to

down this shifting fragment of DNA to reverse its harmful effect in

Progeroid syndromes, such as Hutchinson-Gilford, consist of accelerated aging.

People who suffer from it are characterized by a series of physical features, but this disease is also accompanied by

, such as type 2 diabetes, osteoporosis, cancer and cardiac disorders.

Juan Carlos Izpisúa has dedicated a large part of his career to the study of mechanisms that induce the regeneration of the organism and soften the deleterious processes of aging.

For three decades, he has researched this field as a professor at the Salk Gene Expression Laboratory, and now as director of the San Diego Institute of Science of Altos Labs, a biotechnology company that seeks to ensure that in addition to living longer, we do so with good health. Health.

This June, the Spanish scientist has been recognized with the Ogawa-Yamanaka prize, awarded by the Gladstone Institutes for the contribution to regenerative medicine;

Specifically, the jury highlighted that his research

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Health.

This is how the new laboratories and their lines of research are to slow down aging

• Drafting: MAR DE MIGUELSalamanca

This is how the new laboratories and their lines of research are to slow down aging

And the research published today in Science Translational Medicine contributes to this.

This study presents a way to

, synthesizes Izpisúa.

Of special relevance is that the way to achieve this "does not involve genome editing or proteome modifications, approaches that, apart from their ethical connotations, could induce collateral side effects."

Researchers from the San Antonio Catholic University of Murcia and the King Abdullah University of Science and Technology in Saudi Arabia have also participated in this study.

Transposons or

genes invaded the genome of our ancestors throughout evolution and constitute a very important proportion of our DNA.

They are able to move either through a cut-and-paste mechanism by which they are cleaved and placed in another region, or by retrotransposition, by which the fragment is first translated into RNA and from there originates the DNA that later is inserted in the chosen place.

To this last type belongs the

, which constitutes about 20% of the human genome.

Juan Carlos Izpisúa, Professor of Developmental Biology, at the UCAM HiTechUCAM facilities

The RNA of this

gene plays an essential role during the development of the embryo.

"

. Once it is complete and throughout adult life, the expression levels of LINE-1 are strictly controlled and depend on how the DNA is organized in our cells. "

", explains Izpisúa.

"This organization begins to deregulate with age and the expression levels of LINE-1 tend to increase. In this study we show that this happens due to the gradual loss in the spatial organization of DNA within cells."

Unlike what happens during embryonic development, with age, the movements of these restless genes and their search for a place to settle can bring a certain disorder to the cell.

"At maturity, the higher expression of LINE-1 and a higher incidence of retrotransposition events

.

."

Approach

In cells from patients with Progeria, the researchers found that there were four to seven times more LINE-1 RNA than in cells from healthy individuals.

They also observed that this accumulation occurred before the structural changes in DNA that are associated with the disease began.

Once the genomic alteration was identified, they used molecules to reduce the expression level of LINE1 in cells and tissues.

Specifically, they used

, "small chains of synthetic DNA whose administration in the body is extremely easy," says Izpisúa.

"There is no need to introduce them into cells with vehicles such as viral vectors, they have low toxicity and long duration."

In the specific case of animal models of Progeria, to achieve a lasting and robust effect of rejuvenation and longevity, "we only needed three injections of antisense oligonucleotides, spaced a couple of weeks apart."

The treatment reversed the molecular signs of progeria in isolated cells and extended the lifespan of mice with genetic mutations associated with premature aging

.

In both cases, the expression of genes associated with aging, inflammation and DNA damage decreased.

One hopeful piece of information from this experimental work is that it has used

for some genetic diseases, such as

.

Hence, Izpisúa is confident that this research will transcend the clinical level.

"Our findings offer new insight into the molecular mechanism involved in DNA disorganization within cells. Clinical application of these findings may help restore the cells' epigenome and thus overall health through cellular rejuvenation." ", it states.

In fact, for the scientist "the possibilities of applying these observations to the treatment of accelerated aging syndromes are very high. Likewise, cellular and genetic deregulation tends to increase over time; many diseases are associated with advanced chronological age. In fact, we know that

.Our observations open the door to explore the translation of this technology for cellular rejuvenation in many diseases and also during normal aging, in order to improve and extend our health. in the time".

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