Unity Biotechnology’s science behind their cure for aging

Can we reverse aging? Unity Biotechnology certainly thinks so and it has managed to convince investors to give them $116 million in series B funding to carry out the necessary steps. The company is led by an impressive team of experienced start-up founders including Nathaniel David and Keith Leonard who together had previously started Kythera Biopharmaceuticals which was recently sold to Amgen for $2.1 billion.

Their scientific team is just as strong, composing of Jan Van Deursen, a Professor of Biochemistry and Molecular Biology at the Mayo Clinic and Judy Campisi, Professor at the Buck Institute for Research on Aging. They recently published a paper in Science describing  that removing senescent cells in cell and animal models of atherosclerotic disease inhibited growth of atherosclerotic plaque, reduced inflammation, and improved the structural risk profile of plaques.

Their previous paper in Nature also demonstrated better aging outcomes when senescent cells were removed. They did this by using a transgenic mouse expressing green fluorescent protein (GFP) and FK506-binding protein-caspase 8 (FKBP-Casp8) fusion protein under control of the promoter for Ink4a (a gene active in senescent cells). They then added a drug, AP20187, which dimerizes and activates FKBP-Casp8, triggering cell death specifically in senescent cells (see diagram below for mechanism, taken from an even earlier publication: Baker et al., Nature, 2011).

senescenttgmice

The transgenic mice treated with AP20187 showed a loss of senescent cells in a tissue-dependent manner, with only the colon and liver not showing expected losses of senescence-associated transcripts. Overall, the loss of senescent cells carried out for a period of 6 months when mice were about 12 months of age:

  • prevented age-dependent fat loss
  • extended median life-span by 17-35%
  • increased maximum life-span in mice with mixed genetic background (only when both sexes combined) but not in C57BL/6 mice
  • did not change incidence of tumor formation
  • delayed cataract formation
  • prevented age-dependent loss of spontaneous motor activity and exploratory behavior but did not prevent loss in memory, muscle strength, or coordination and balance.
  • reduced age-related impairment of kidney function
  • prevented age-associated increase in cardiac myocytes
  • increased tolerance of mice to cardiac stress

Oh and it also made the mice look younger:

apmice

Just look at the luscious fur coats of those AP20187-treated mice!

The only challenge with this approach is it requires genetic engineering. However it does identify the role of senescent cells in age-related diseases, and finding a drug/molecule to get rid of them may work just as well. Previous attempts to stall ageing using Resveratrol has not shown such dramatic effects though in a recent trial it does seem to improve outcomes in Alzheimer’s disease patients. Diabetes drug, Metformin, is also being touted as the best hope as an anti-aging medicine and recently won FDA-approval for a clinical trial to be used for that purpose called Targeting Aging with Metformin (TAME).

Aging was thought of as a mysterious process but it appears we are getting a little closer to understanding it. Let’s hope we can prevent hair-fall and cataracts in our lifetime!

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