07 February 2019

Senostatic – stopping aging

HIV drug stopped rampant transposons in aging mice

And saved them from the development of many senile diseases

Polina Loseva, "The Attic"

Aging of the body is accompanied by inflammation in many tissues at the same time. Recently, a theory has emerged that the cause of this inflammation is in transposons, remnants of ancient viruses that live in our genome. To stop the reproduction of transposons, scientists used antiviral drugs that are now being treated for HIV. The results were not long in coming: human cells stopped secreting pro-inflammatory proteins, and adult mice had fewer age-related diseases. The next step should be clinical trials in humans.

It is still unknown where the retrotransposons came from. They were probably free-living viruses once. They lived in much the same way as modern retroviruses (i.e., for example, the human immunodeficiency virus): genetic material entered the cell in the form of RNA, on its basis a protein was built – reverse transcriptase (revertase), which copied information from RNA to DNA. The DNA genome of the virus was embedded in the DNA of the cell, then the cell read it in the form of RNA – and the cycle closed, the virus could stay in the cell or go outside, surrounding its RNA with proteins. One can imagine that some retroviruses have lost the ability to leave the cell, and with it their independence. They remained in our DNA and became known as retrotransposons. All they can do is rewrite RNA into DNA and embed themselves in a random place in the genome.

Anyway, now only one full–fledged retrotransposon "lives" in human DNA - LINE-1, or L1. And it is considered one of the possible causes of aging. First, it can cause a tumor transformation if its copy gets inside the gene that controls cell reproduction. Secondly, jumping over the genome, it increases the number of breakdowns and mutations, and the cell reacts to this by stopping dividing. Thirdly, in response to the accumulation of L1, the cell begins to produce interferons, and those, in turn, cause inflammation in the surrounding tissues.

An international team of researchers treated human cells with lamivudine, an anti–HIV drug that blocks reverse transcriptase. As a result, the number of retrotransposons in cells decreased, as well as the expression of pro-inflammatory genes, including interferons. Then scientists tested the effect of lamivudine on elderly (26 months, average life span 2-3 years) mice. In two weeks, the drug helped the mice partially get rid of inflammation. And a long course (from the 20th to the 26th months of life) of the drug prevented exhaustion, damage to the renal vessels and atrophy of skeletal muscles - sure signs of mouse old age.


Article by De Cecco et al. L1 drives IFN in senescent cells and promotes age-associated inflammation published in Nature.

Researchers call their drug senostatic (stopping aging) – as opposed to senolytics, drugs that remove old cells from tissues. Despite the fact that scientists have not yet achieved the complete disappearance of signs of inflammation in mice, they talk about the need for clinical trials on humans. As mentioned in a press release from Brown University (HIV drug could treat Alzheimer's, age-associated disorders), study leader John Sedivi, lamivudine has been used in practice since 1995, its pharmacological activity and safety have been well studied, and now he would like to check whether lamivudine can prevent the development of age-related diseases, such as Alzheimer's or arthritis.

The fact that you can fight old age by taking control of the rampant retrotransposons on DNA was mentioned at the conference "Ways to achieve active longevity", which was held in the spring of 2018 in Kazan. 

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