3 “Hallmarks of Ageing” and Companies Solving them

Source: Medical News Today

I discussed the search for super-human longevity in my earlier post “Living to 100 and Beyond” and in this post, I am looking to cover 3 “hallmarks of ageing” and solutions that different companies are developing to target these which will change the way you think about ageing (or motivate you to take a deeper look into the space if you haven’t already given it serious thought).

Scientists often discuss ageing as the sum of the damage rather than attributing cause-effect relationships between the symptoms and ageing. Scientific consensus converges on 9 “hallmarks of ageing” of which three are relevant for the purposes of this post:

• Telomere attrition: Telomeres are protective caps at the end of DNA strands which prevent DNA from fraying; with each cell division (and due to stress factors), telomeres grow shorter as we age and DNA becomes more exposed to damage
• Cellular senescence: While certain cells commit “apoptosis” / cellular suicide when they are subjected to irreparable DNA damage, certain other cells resist apoptosis and become “senescent”, firing off harmful chemical signals to other healthy cells thereby damaging the entire cellular system
• Stem cell exhaustion: As we age, we run out of stem cells, which have the potential to replace other damaged cells (as needed), due to several other hallmarks of ageing such as senescent cell secretions, DNA damage etc.

There are many companies solving ageing related problems but I found the following particularly interesting.

Life Length targeting telomere testing and diagnostics

Decrease in telomere length correlates strongly with higher age and disease risk.

Source: 2012 Aubert et al. Notes: “The median telomere length in nucleated blood cells from 835 healthy individuals ranging from birth (umbilical cord blood) to 102 years of age were measured by flow FISH. The results were used to calculate the telomere attrition over time using linear regression in three age segments. A. Median telomere length in lymphocytes (black dots). B. Median telomere length in granulocytes (grey dots). Breakpoints in the piece-wise linear regression lines are marked by rectangles and the three age groups are marked by dotted vertical grey lines at 1 and 18 years. On average 8 individuals were tested per age-year. C. At any given age, a wide range of telomere length was observed and the decline in telomere length with age in lymphocytes was more pronounced than in granulocytes. The shaded area represents the estimated length of subtelomeric DNA. Note that in older individuals, on average only 1–2 kb of telomere repeats were present in lymphocytes.”

While multiple companies are offering supplements that claim to reverse telomere attrition, majority of the claims lack scientific evidence. Some such companies have also been the target of various lawsuits and regulatory backlash.

The science behind telomeres and telomerase (enzyme responsible for maintaining telomere caps) is still evolving and only recently has a Harvard lab been able to identify molecules that have been proven to reverse cellular ageing in stem cells.

Life Length caught my eye as it appears to be a very sensible company focusing its attention on telomere measurement and diagnostics. It is a technology company that has a clear product (its telomere testing services) and a healthy client base (including AgeX, a Juvenescence subsidiary).

Life Length checks off my boxes on the business model being lucrative in the short / medium term as well as offering upside in the long term. While it provides testing services currently (and is revenue generative in the present), it is also well poised to enter the ageing treatment market directly once there is more concrete evidence of results in human trials.

Established in 2010 and headquartered in Madrid, Life Length has received €3 million worth of strategic funding in 2018 from the Japanese multinational Yamada Bee Company as well as additional €1 million funding from Spanish multinational Grupo Alter. It also raised over £2.1 million in a crowdfunding round in 2019.

Unity Biotechnology targeting cellular senescence

Source: Unity Biotechnology Corporate Presentation November 2020. Notes: (1) Coppe et al. Annu Rev Pathol 2010.

Cellular senescence is one of the hot topics in gerontology, partly because it has some immediate applications to ageing related problems such as in the treatment of age-driven neurological and ophthalmological conditions.

Senolytic medicines work by removing senescent cells from the bodies of ageing animals and have shown promise in early stage trials. Many such trials are still underway at Unity Biotechnology to assess the effectiveness of senolytic treatments.

Unity is one of the few biotech companies that is publicly listed — it trades on the NASDAQ and has witnessed a recent steep fall in share price of c.67% in one day (in mid-Aug) when it announced that one of its molecules in clinical trials which was targeting osteoarthritis was unsuccessful in proving pain reduction in patients.

Unity has other clinical trials underway the results of which should drive future value but the debate continues on whether early stage biotech companies make good public investments as their share prices are very volatile to newsflow around clinical data.

The website and filings are a welcome change from other companies in the space (partly due to the public status) and provides sufficient reading material to deduce an investment case.

Tree Frog Therapeutics targeting stem cell manufacturing

Cell therapy using pluripotent stem cells (self-renewing master cells able to potentially able to produce almost any cell or tissue the body needs) is a promising new avenue which could change many lives by treating a vast pool of diseases such as neurodegenerative (Parkinson’s, Huntington’s) diseases, heart failure, diabetes etc.

While traditionally scientists have been producing stem cells in petri dishes, this method is space intensive (one liver taking the equivalent of a football field to grow) and the throughput of cells is low as stem cells are very fragile.

Tree Frog has developed C-Stem, a technology which allows stem cells to be produced in bulk by encapsulating them in an environment which mimics the human body’s physiology. The mass production at lower costs (due to efficiency of production process) will enable Tree Frog to make cell therapy available worldwide at a fraction of the current cost.

Source: Tree Frog Therapeutics

In their own words, Tree Frog is building a “stem-cell factory to treat millions of patients”.

Tree Frog has raised over €10m in 2019 with bulk of the funding coming from a €7m seed round (participation from XAnge, Galia Gestion and historical investors Irdi Soridec, Aquiti Gestion and SATT Aquitaine) and €3m non-dilutive public grants.

Follow-up posts will cover:

(i) Other hallmarks of ageing

(ii) Other interesting companies making strides in the space