The Agenda 👇
News bulletin 📰
mTOR, what is it good for?
Recent funding in longevity 💰
Upcoming events 📅
Jobs in longevity 🧑💼
1/ News bulletin 📰
🇮🇪 Is Ireland the new European longevity hotspot? - fast becoming a leader in clinical trials, Dublin is attracting longevity researchers and science organisations
🩹 Epigenetic age acceleration is correlated with mortality - study in women found lower epigenetic age acceleration associated with longer survival and better functioning
💻 StarkAge Therapeutics collaborates with Lille University to strengthen its platform ExoCise - multi-omics player hopes to identify relevant targets for its immunotherapy approach
🧠 Alzheimer’s Disease breakthrough with genetic link to gut disorders - large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer’s disease and gastrointestinal tract disorders
🧬 Genetic study demonstrates that alcohol accelerates biological ageing - new analysis published in Nature by Oxford Population Health show that alcohol damages DNA by shortening its protective telomeres
2/ mTOR, what is it good for?
All cells have a variety of pathways to control their individual growth, dependent on their tissue’s needs, the environment and the resources available locally. In human cells, one of the most important pathways for cellular growth and metabolism is the mTOR signalling pathway.
mTOR is among the hottest targets at the moment for longevity therapeutics, with Cambrian Biopharma having recently licensed novel compounds from Novartis to target the mTOR pathway. To uncover what Cambrian Biopharma (now named Tornado) and others are up to, this week I have pulled together a deep dive into mTOR and its role in ageing.
The mTOR pathway is among the most powerful promoter of cell survival in mammalian cells through the upregulation of protein and lipid synthesis, boosting of cellular metabolism, and the downregulation of cell suicide pathways that would normally cause the cell to rupture.
mTOR stands for mechanistic target of rapamycin. Rapamycin is an immunosuppressant drug that was first discovered in a bacterium found on Easter Island in 1972. Among the first effects rapamycin was discovered to have, was on TOR genes, which is where the name mTOR came from.
There are 4 main functions of the mTOR signalling pathway: cell growth and proliferation, angiogenesis (new blood vessels to feed the growing tissue), bioenergetics through nutrient availability and metabolism boosting, and cell survival through decreasing cell self-destruction and triggering DNA repair mechanisms.
The mTOR pathway is activated by a series of growth factors which act as signalling molecule outside of the cell. These growth factors bind to tyrosine kinase receptors (TKRs) in the cell membrane, which in turn activates the mTOR pathway:
The enzyme PI3 kinase is activated by phosphorylation
PI3 kinase phosphorylates the substrate PIP2 into PIP3
PIP3 activates the enzyme Akt, which is responsible for activating mTOR
mTOR goes on to activate a series of transcription factors, which travel into the nucleus of the cell and control the transcription and expression of genes involved in cell growth and metabolism.
mTOR typically functions as part of a protein complex, which is where several proteins are bound together and act as a single unit. There are two types of mTOR complex: mTORC1 and mTORC2, which comprise slightly different proteins, but they each stabilise mTOR and help it bind to its target receptor.
mTORC1 binds to and activates the ribosomal protein S6K, which is responsible for increasing protein synthesis. mTORC1 also inhibits the activity of 4EBP1, which normally inhibits protein synthesis. This complex additionally plays a role in promoting lipid synthesis, mitochondrial biogenesis, and downregulating cell-destruction.
Since mTOR plays an active role in the activation of genes related to cell growth, any defects within mTOR function can lead to cancer. Several genes activated by mTORC1 and mTORC2 play a role in preventing apoptosis of cells and regulate nutrient uptake, which if disrupted, can cause uncontrolled growth of cells and the formation of a tumour.
Hyperactivation of the mTOR pathway is not without problems however and is thought to be among the leading causes of cardiac hypertrophy, which is major risk factor for cardiac morbidity and cardiac-related mortality.
Ageing is a complex process that has many factors at both the genetic, cellular, and environmental level, but the mTOR pathway has been shown to have a central role in the process. From cellular senescence regulation to the immune response, mTOR’s regulation is directly involved in cellular and tissue health. As the number of studies surrounding mTOR and its role in ageing grow, we can expect to see more biotech companies enter fray laser focussed on this target.
3/ Recent funding in longevity 💰
Molecule raises $12.7m in Seed funding to build its decentralised science and biotech platform
Juvenescence invests in Chrysea Laboratories to develop and commercialise one of their products
4/ Upcoming events 📅
🇮🇪 The Longevity Summit Dublin takes place this year on 18th-20th of September in Ireland! Conference will feature some of the world’s renowned longevity experts like George Church (Professor of Genetics, Harvard Medical School), Aubrey de Grey (Co-Founder, SENS Research Foundation), Evelyne Yehudit Bischof (Associate professor, internal medicine specialist, Longevity physician at Human Longevity Inc.), Jim Mellon (Chairman & Co-Founder Juvenescense ; Global Investor ), Greg Grinberg (Actualfood Founder & CEO), Phil Newman (Founder, First Longevity, Editor-in–Chief Longevity.Technology), and many more.
🇬🇧 The Nutrition and the Biology of Ageing conference is being hosted by the Biochemical Society and the British Society for Research on Ageing, and will feature Brian Kennedy of the National University of Singapore. Conference will take place at University of Kent Canterbury, UK on September 12-14.
🇨🇭 On September 28-30 the Longevity Investors Conference (LIC) are hosting their third annual conference in Gstaad! It will be a great opportunity to learn about diverse longevity investment strategies, network with like-minded leaders, and get acquainted with the recent scientific breakthroughs by the leading longevity experts in the world.
5/ Jobs in longevity 🧑💼
Alchemab // Bioinformatician // Cambridge, UK
Calico // Senior Data Scientist - Systems Genetics // South San Francisco, CA
BioAge Labs // Manager, Business Development // Remote, US
Turn.Bio // mRNA Synthesis & Production Scientist // Mountain View, CA
BioSplice // Senior Research Associate, Tumour Biology // San Diego, CA