Development of model systems, biomarker and compounds against senescence-driven age-related pathologies

The public summary consists of 250 to max. 300 words. The summary is intended for a broad audience with a secondary education language level. In short, the public summary describes the who, what, where, when, why and how of the project. Focus on the core message of the project instead of elaborating on explanations and background information.  
 
Health~Holland would like you to follow these guidelines: 

• First paragraph: short summary of the whole project (see point 4) with a highlight on the (newly) established public private partnership.   
• Second paragraph: introduction on the societal/economic impact and relevance of the health/disease/vital functioning/etc. and why innovation is necessary. Make use of numbers, statistics, or rankings to illustrate the relevance of the project to the lay public.  
• Third paragraph: explanation of the project’s approach and conceptualisation, and how this innovative solution will contribute to the previously described societal challenge(s). 
• Fourth paragraph: description of deliverables and, if the project is finished, an illustration of the (end)results.  

With an aging society, age-related diseases will become an increasing problem. In SMARTage, three academic centers (UMC Utrecht, UMC Groningen and Leiden UMCU) teamed up to discover new ways of combating harmful cells and partnered with Cleara Biotech B.V. to develop new therapeutics to combat these.  

We are getting older, but the number of healthy years is not linear. The EU has seen an increase in people over 50 that suffer from 2 or more chronic conditions from 38% in 2006 to 42% in 2015, and anticipated to reach up to 45% by 2030. Over 20,000 publications have now connected a process called cellular senescence to age-related diseases in laboratory animals. Counteracting it has shown a staggering extension in median lifespan by 17% to 35%, but above all a major extension in healthspan. Unfortunately, translation to humans has been challenging, at least in part because there are multiple types of senescence. 

The team of SMARTage has extensive, proven, background in understanding the molecular hallmarks of senescence (50+ publications in the last 10 years and several patents). Together, it set out to develop methods to detect new types of cellular senescence and design compounds for elimination thereof. This was performed in cells in culture 3D organoids and mice.  

Ultimately, SMARTage delivered new methods for detecting senescence subtypes through development of new multiplex imaging techniques (I). It characterized at least 3 subtypes and at least two methods for elimination, which can be commercially progressed towards clinical (II).  It identified panels of protein, metabolite, coding and non-coding RNA panels to detect these subtypes (III). It set up new models to investigate how these subtypes interact with their environment and impair the biology of nearby cells (IV). It set combined I-III to design and validate new anti-senescence compounds IV).  

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