ARDD 2021: DNA repair, mitochondrial enhancement, gene editing, and how a new era for longevity will help us beat age-related disease.
After three great days at the 8th Aging Research and Drug Discovery Meeting (ARDD), more leaders in the longevity space have shared their cutting-edge research, providing insight into new ways of progressing preventative and restorative therapies that target the decline associated with age.
Yesterday we heard from Björn Schumacher from the University of Cologne, who discussed the genomic maintenance mechanisms involved in aging. He explained how an insulin-like longevity assurance pathway regulates an organism’s response to DNA damage, and proposed two strategies of longevity. First, using DNA repair mechanisms, which are essential to slow aging, as defects can accelerate aging – even from the first decade in our lives.
Second, Schumacher explained how longevity protection mechanisms can be utilised alongside DNA repair to raise the threshold at which DNA damage becomes detrimental for tissue functionality within the body. Both strategies could have a profound effect on delaying aging if used together. He showed how his team’s research has led to the conclusion that organismal responses to DNA damage regulate somatic and germline maintenance, highlighting the importance of the soma in regulating genome stability in the germline, and further noting DAF-16-mediated longevity pathways as a regulatory method of somatic maintenance amid DNA damage.
The day showcased a variety of longevity research, we heard more about the importance of focussing on mitochondrial targets in relation to finding age-related therapies. Karl Lenhard Rudolph from the Leibniz Institute on Aging spoke on mitochondrial enhancement and its relationship with late life dietary restriction, enabling improvements in stem cells and lifespan. While recognising the positive effects seen with dietary restriction across organisms, Rudolph addressed the worrying data that saw this method losing efficacy when restriction is started late in life. When looking at reduction of mortality rates lifelong dietary restriction shows a reduction in mortality rate, however late life dietary restriction has very little effect.
Rudolph explained how his lab’s research in mice models has led to the hypothesis that mitochondrial activation seen in response to nutrient deprivation is required to activate health promoting stress signals. This is due to failed responses seen in older mice under nutrient and dietary restriction, showing that they cannot activate mitochondria efficiently and so do not produce stress signals in the same way. He finished by showing the interesting effects of Metformin and how, when used independently in old mice, no mitochondrial activation was seen. However, when used in combination with nutrient restrictions, mitochondrial activity doubled, showing yet again why mitochondrial targets are a pillar of longevity research.
A new era for longevity
The day was rounded off with some great insights on longevity biotechnology with Kris Verburgh from Longevity Vision Fund. With a punchy “new era for longevity” opening statement, he gave a brief introduction into technologies in development that have the potential to extend both healthspan and lifespan.
Verburgh spoke about gene therapies and gene editing and the progression from 2012 with the discovery of CRISPR-Cas9, to today’s base editors and their phenomenal potential to cure disease through targeting single point mutations. He described ‘Gene editing 3.0’ approaches, noting them as pioneering gene writing mechanisms, and highlighted Tessera Therapeutics, a company currently creating both DNA and RNA transposons that is showing the potential of these more accurate gene editing therapies by inserting specific gene sequences into the genome.
Verburgh also discussed a wide range of interesting advancements in novel biotechnology, from gene editing to preventative medicine technologies, including the Galleri test, which detects more than 50 types of cancer, shifting diagnostics away from cells to blood. With a 99.5% specificity, the test aims to revolutionise cancer detection as 71% of cancer deaths are caused by cancers without recommended screenings. This is just one example of the many technologies already developed at the beginning of this biotech revolution.
Verburgh ended by stressing the importance of addressing aging in order to keep people healthier for longer, and that novel biotechnologies will provide the best answer to tackling age-related disease and leading the health and longevity industry into the future.