Proteomics and biological age measurement

AgeCurve closes in on first round investment as it builds its team with the support of key opinion leaders in aging research.

UK start-up AgeCurve is focused on the measurement of aging and claims to be the first start-up to use direct-to-consumer personal proteomics to provide deep age profiles to end users.

Founded in 2015, the Cambridge-based company is based on the principle that human aging is actually “agings underneath” – the results of many separate processes mainly governed by changing protein functions.

From a simple saliva sample, AgeCurve generates deep age profiles by sequencing and quantifying thousands of human proteins to assess different aspects of the ongoing biological aging process.

To understand where AgeCurve is positioning itself, we spoke to the company’s founder, Attila Csordas, a proteomics bioinformatician with a background in mitochondrial and stem cell research.

Longevity Technology: How did AgeCurve get started?
Attila Csordas: I recall decidedly picking the problem of aging and the corresponding project of healthy longevity as my exclusive professional motivation at the age of 14. Biological aging presented itself to me as the most exciting scientific puzzle to work on, rather than a source of existential threat. At that point it meant being interested in the mitochondrial theory of aging and starting my diary with some ‘hypotheses’ on that and some mitochondrial therapy ideas to slow down aging.

After starting out as a mitochondrial and stem cell researcher, I turned my attention to proteomics and had been working as a proteomics bioinformatician for 9 years at the PRIDE database at the EBI in Hinxton, UK, since 2010. This gave me plenty exposure to understand the potential and limits of high-throughput proteomics and other types of datasets. Completing an MS degree in philosophy focusing on the moral, political, philosophical problems around longevity technology helped me to develop a strong argumentative stance around this topic giving me confidence to frame this problem and project both scientifically and on the level of public policy.

AgeCurve has been born out of me being at the intersection of aging/longevity research and proteomics. What is even more important is that I could quickly build a word class scientific and technical team covering both sides, including stellar advisors like Daniel Reda and Aubrey de Grey and also have the occasional scientific support of people like Kathryn Lilley, proteomics professor at Cambridge University.

Proteomics technology and aging/longevity science, this is where we have our competitive advantage.

Longevity Technology: How does AgeCurve set itself apart in the field of age measurement?
Attila Csordas: In striking contrast with the practice of personal genetic testing, AgeCurve’s focus is on biological aging, and it is not a disease in the clinical sense, yet it is the biggest risk factor of chronic age-associated diseases. Biological aging is something that happens with everybody. I am having it, you are having it, and it does not get any better with time. Additionally, biological aging is really ‘agings underneath’, the results of many separate processes mainly governed by changing protein functions. Hence, the AgeCurve experience starts with protein based aging scores, not health scares, as genetic tests do.

What this all means is that we do proteomics and we are the only ones doing so in a direct-to-consumer setting and focusing on capturing the dynamics that is essential in understanding biological aging.

The scientific problem of understanding biological aging is two-fold: First, we want to understand what processes change with age and how. Second, we want to understand the disconnect between chronological and biological aging. Both are needed in order to develop robust interventions to slow or to stop particular negative aging processes.

Measuring changing protein quantities throughout our life trajectories will have a lot to add to unfold these problems. Let me highlight two fresh studies to show accumulating evidence of proteomics in delivering aging signatures.
New proteomic discoveries reveal a link between levels of certain proteins in human plasma and aging.
The first study, from last year, by the Wyss-Coray lab at Stanford, used 4000+ blood samples, from people aged 18-95, measuring ~3000 proteins to show three jumps in the quantities of plasma proteins at different ages indicating bigger changes in life trajectory [1]. Also it showed 373 proteins highly accurate in predicting chronological age.

The second study has been published a couple of weeks ago by the Schilling Lab in the Buck Institute, and they have built a proteomic atlas of soluble and secretory proteins associated with cellular senescence, one of the hallmark aging processes [2].

Longevity Technology: How does AgeCurve work?
Attila Csordas: At AgeCurve, we quantify thousands of proteins in saliva and select the ones showing relevant patterns to build biological aging scores, amongst others. Based on non-invasive saliva collection (the emerging standard of direct-to-consumer omics profiling), the sample is sent to our US partner lab for the mass spec runs and the results are delivered to our users a couple of weeks later (standard timeframe) as a native web application accessible with digital devices.

We already capture bits and pieces of the majority of the nine molecular hallmark processes of aging [3] with many customised protein stories: proteostasis, senescence cells, innate immunity – inflammaging, cellular energy/respiration. And we are adding more stories since we have thousands of sequenced/measured human proteins. This comprehensiveness is unprecedented on the market.

Although aging is not a disease, clinically speaking, we have started to work with clinicians on separate continents to see how our high-throughput protein measurements and aging-focused computational resources can provide clinically actionable information.

Longevity Technology: What are your primary objectives and next key milestones at this point?
Attila Csordas: The polished and rather empty answer is to find a product – market fit in the next two years. The real answer is to build a committed user base and educate them, including clinicians. One needs to work a lot on this market and finding our way into clinics, which are conservative for several reasons, is a challenge. We are ready to meet this challenge.

We are about to close our first serious funding round. Now is a good time to join.
These are very early days within the Longevity industry, so we must be flexible to seize the opportunities and answer the challenges. A distinctive feature we have, looking at other start-ups in this space, is that I’d like to build an aging-savvy company from the ground up. This is the question of a fitting company culture and it has two parts.

One is to ensure knowledge sharing related to aging/longevity so even a devops or a sales person has sufficient understanding around the scientific basis of what we do. Having an already articulated longevity motivation on joining such a team is a must.

The other part is age diversity, to have a team with people from all working generations – that has been shown to be a real asset when tackling complex problems. We are not building a dating app for 20 year olds.

Longevity Technology: Can you share your target outcome from your planned workshop: Towards a Consensus Definition of Biological Aging?
Attila Csordas: Current clinically focused biological aging research, or translational geroscience is going through incredible progress. However the core of this emerging knowledge is not reflected in a consensus, yet flexible and actionable definition of biological aging. The workshop is trying to make the first steps to address this problem by looking into several candidate definitions and underlying theories from different, biological, clinical and computational angles.

As a target I’d like to see a comprehensive list of criteria and necessary components identified and hopefully one consensus definition emerging to cover those components and meet these criteria. This might then be turned into a proposition for larger audiences.

Already confirmed speakers are key opinion leaders of aging research like Lynne Cox, Aubrey de Grey, Nir Barzilai amongst others. We will also have junior researchers from the Cambridge area contributing with different insights.