[ExI] A new anti aging drug

Rafal Smigrodzki rafal.smigrodzki at gmail.com
Sat Feb 6 14:17:20 UTC 2016

On Fri, Feb 5, 2016 at 4:51 PM, John Clark <johnkclark at gmail.com> wrote:

> ​Researchers report in the ​
> Feb. 3
> ​issue of ​
>  Nature
> ​ that a drug called
> AP20187
> ​ increased the lifetime of mice by 30% even if the treatment isn't
> started till middle age:
> http://www.sciencemag.org/news/2016/02/suicide-aging-cells-prolongs-life-span-mice

### It should be mentioned that AP20187 is not a likely life-extesion drug.
It is a homodimerizer designed to induce interactions between two DmrB, or
FKBPv domains. The compound is commercially available and by itself it
doesn't have any biological relevance, since it specifically binds to a
mutated version of FKBP (FKBPv), which is absent in normal mammals.

Here is what was shown in the article: First they introduced a genetic
detector of senescence into mice by genetic engineering. The detector is an
artificial gene that contains an ink4a promoter that controls FKBPv-cas8
expression. Ink4a is a protein found in senescent cells of normal mice. In
the senescent cells of genetically engineered mice ink4a will bind to the
ink4a promoter and produce FKBPv-cas8. FKBPv-cas8 is an artificial protein,
not normally found in animals. It has two parts: cas8 and FKBPv. Cas8 is a
caspase, which kills cells if activated. FKBPv is a protein domain which
binds to AP20187. If you have FKBPv in cells and add AP20187, the FKBPv
will be induced to form homodimers (two identical FKBPv molecules stuck
together by the action of AP20187). If the FPBPv molecules are designed to
have cas8, their homodimerization will bring the cas8 domains together, and
activate them, causing cell death. In this way you can induce controlled
killing of cells of your choice, in this case determined by the presence of
ink4a - in other words, you can specifically, using genetically engineered
detector and effector molecules (which here they call INK-ATTAC), kill
senescent cells.

The article basically repeats the group's previous work, published in 2011 (
 2011 Nov 2;479(7372):232-6. doi: 10.1038/nature10600.) but in different
strains of genetically engineered mice, and shows that selective ablation
of some senescent cells seems to make mice healthier. Not all senescent
cells were removed, since the INK-ATTAC doesn't seem to work in colon and

This is very neat but it doesn't have a direct application in humans,
unless you wanted to genetically modify babies to carry the INK-ATTAC
killer gene. However, it does open interesting research directions. One can
think about many ways of specifically killing senescent cells in adult
humans and I would not be surprised if some of them were tried in the next
10 - 15 years.

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