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Longevity: First principles of disease

Why we're excited about it

At DSV we always aim to look beyond the immediate symptoms and seek to understand and address the complexity of upstream failures in disease. Whether this be moving beyond the predominant protein aggregation hypothesis in Alzheimer’s to develop a new hypothesis or finding new ways to address the phenotype in oncology rather than follow the crowd into immunotherapy.

The field of longevity isn’t some strange obsession with living forever but rather ensuring that the last 20-30 years of life are happy and free from age related diseases. The aim is to achieve this by focusing on a classifiable sub-types of molecular level damage which accumulates throughout life and appear to underlie most age-related disease.

This doesn’t mean there’s anything easy about reversing what is a complex web of failing homeostasis, especially as in many cases it’s not detected until the damage is irreparable. However, we’re now at a point in scientific development where a rudimentary toolset exists that may be able to understand and address much of this upstream damage.

Initially we will focus on the following four principal areas. Clearly there is a high degree of cross over between areas and that’s exactly the point. Whilst the research base is principally deep in one given area, and typically for a given disease, we are looking to extract principles and generate therapies that apply across multiple systems, which if addressed could provide a mechanism to reduce the severity of multiple diseases.

1) Cellular regeneration

The regeneration of organs via addition of stem cells or directed differentiation or state change across tissues including bone, muscle, reproductive, vasculature, neural, liver, kidney, the immune system, hormone production and stem cell exhaustion generally.

2) Molecular level damage buffering and rebalancing

Repairing or assisting damaged cellular sub-systems such as by-product removal, damage to macro molecules, protein accumulation, homeostasis of hormones, micro-nutrient, enzymes and antioxidants, mitochondrial dysfunction, glycation and cross-linking, autophagy and clearing senescent cells.

3) Messaging and signalling pathways

Addressing failures at the network and signalling pathway level both intra and intercellularly. Including transporters of small molecules, damaged ion channels, G-protein-coupled receptors, receptor kinases / phosphatases, second messengers, messaging that underlies metabolic function and cellular structure broadly, immune signalling defect, inflazome / inflammation and endocrine homeostasis.

4) Error correction

Ensuring homeostatic levels of gene expression, addressing undesirable mutations, epigenetic errors in transcription, post transcriptional processing, post translational modifications, interactions among gene products and proteostatis.

Longevity: First principles of disease

Why we're excited about it

At DSV we always aim to look beyond the immediate symptoms and seek to understand and address the complexity of upstream failures in disease. Whether this be moving beyond the predominant protein aggregation hypothesis in Alzheimer’s to develop a new hypothesis or finding new ways to address the phenotype in oncology rather than follow the crowd into immunotherapy.

The field of longevity isn’t some strange obsession with living forever but rather ensuring that the last 20-30 years of life are happy and free from age related diseases. The aim is to achieve this by focusing on a classifiable sub-types of molecular level damage which accumulates throughout life and appear to underlie most age-related disease.

This doesn’t mean there’s anything easy about reversing what is a complex web of failing homeostasis, especially as in many cases it’s not detected until the damage is irreparable. However, we’re now at a point in scientific development where a rudimentary toolset exists that may be able to understand and address much of this upstream damage.

Initially we will focus on the following four principal areas. Clearly there is a high degree of cross over between areas and that’s exactly the point. Whilst the research base is principally deep in one given area, and typically for a given disease, we are looking to extract principles and generate therapies that apply across multiple systems, which if addressed could provide a mechanism to reduce the severity of multiple diseases.

1) Cellular regeneration

The regeneration of organs via addition of stem cells or directed differentiation or state change across tissues including bone, muscle, reproductive, vasculature, neural, liver, kidney, the immune system, hormone production and stem cell exhaustion generally.

2) Molecular level damage buffering and rebalancing

Repairing or assisting damaged cellular sub-systems such as by-product removal, damage to macro molecules, protein accumulation, homeostasis of hormones, micro-nutrient, enzymes and antioxidants, mitochondrial dysfunction, glycation and cross-linking, autophagy and clearing senescent cells.

3) Messaging and signalling pathways

Addressing failures at the network and signalling pathway level both intra and intercellularly. Including transporters of small molecules, damaged ion channels, G-protein-coupled receptors, receptor kinases / phosphatases, second messengers, messaging that underlies metabolic function and cellular structure broadly, immune signalling defect, inflazome / inflammation and endocrine homeostasis.

4) Error correction

Ensuring homeostatic levels of gene expression, addressing undesirable mutations, epigenetic errors in transcription, post transcriptional processing, post translational modifications, interactions among gene products and proteostatis.

Join

We’re currently recruiting for a Founding Analyst to lead our venture creation activity in Longevity.  More info here.

If you are interested in joining a project, pitching an idea, investing or other collaboration opportunities in this area, please get in touch via hello@dsv.io