Aging is the number one cause of disability and morbidity in our society, and the
cause of the biggest drain of resources on the healthcare systems in the Western
world.
FAB is working to boost the body’s defences against this damage that
accumulates
with aging. Our bodies have their own defences, but they decline with age. A
decade’s research by FAB’s scientific founder Dr. Bains has identified how that
process could be ‘tuned up’ in cells
as we age, extending the healthy life of our cells and hence of our bodies.
See the other sections for more background on the chemistry and biology
of aging,
and how Five Alarm Bio is targeting it.
In a landmark paper, Manuel Serrano and his colleagues listed nine types of
failure
that happen in our cells and bodies as we age:
1. DNA damage and instability
2. Altered cell:cell communication
3. Epigenetic alteration
4. Loss or protein quality control
5. Accumulation of senescent cells
6. Running out of stem cells
7. Mitochondrial damage and dysfunction
8. Failure in cellular sensing of nutrients
9. Telomere shortening
Many of these come down to accumulated chemical damage. This is directly seen in
the accumulation of compounds called Advanced
Glycation Endproducts – AGEs – which damage proteins inside and outside cells,
and are the targets of several anti-aging programmes and drugs.
Our approach is to look at the more subtle effects of chemical damage,
the degradation
of cellular accuracy, and target this for redress.
Our bodies are assaulted by chemicals every second. Even if we drank nothing but
pure water and ate only the cleanest, healthiest food, the oxygen in the air we
breathe is a reactive substance that damages us, and our own metabolisms
generate ‘accidental’ products that are harmful.
Why are all these random chemicals bad? In a landmark paper published in 2016,
Five Alarm Bio’s founding scientist William Bains described why any chemical
that was not part of the body’s healthy biochemistry is bound to interfere with
the actions of enzymes and other proteins throughout the body. This is not just
obvious chemical attack. Even small changes in how a protein functions can
disrupt the delicate balance of a healthy cell.
Luckily our cells have many defences against such disruption, but they gradually
fade with age. A key development of the 2016 work was seeing how those defences
could be encouraged to work just a bit harder, to counter the effect of
chemistry and hence extend healthy lifespan. This is the technology that Five
Alarm Bio is implementing.
Five Alarm Bio's foundational science has shows that targeting the chemical
damage of aging can modulate a range of fundamental aging processes. We have
used a model 'probe' compound to test what effects modulating Five Alarm's
target mechanism will have. Working with primary human skin cells, we have shown
that we can reduce cell senescence, reduce the chemical damage that accumulated
in aged cells, and reduce the decline in their ability to heal a 'wound' in cell
culture. We have also worked with Magnitude Biosciences to test the effect of our probe on
aging in the nematode worm C. elegans. C. elegans is a well-tested
model for aging in animals, and has been the organism that pioneered many
breakthroughs in aging research. Magnitude have shown that our probe extends the
healthspan of C. elegans by ~40%.
Future programmes will target this core technology
to specific organ systems and their diseases. Our initial programmes are in
Chronic wounds (for which we have been awarded a Biomedical Catalyst grant),
sarcopenia, and an evaluation of whether this has the potential to be a
treatment for Alzheimer's Disease.
