Fourth SENS Roundtable

"Enhancing lysosomal catabolic function using microbial enzymes"
July 26th, 2004 at the National Institute on Aging, Bethesda, MD

Organizer: Aubrey de Grey
Click here to read the paper written by the participants.

Original Summary Text

This meeting was convened at the instigation of, and largely supported by, the US National Institute of Aging in Bethesda, at whose offices it took place. Two senior NIA administrators attended IABG 10 and were particularly enthused by the talk given by John Archer summarising preliminary work to explore the feasibility of a proposal I had originally made in 1999 and on which I had published a short review in 2002. They encouraged me to take the idea further with this meeting.

The idea in question is based on the observation that several of the commonest and most intractable age-related diseases are associated with, and with varying degrees of confidence believed to be caused by, the intracellular accumulation of substances that impair cellular function and viability. Reversing this accumulation may thus be valuable, but has proven challenging, doubtless because substances resistant to cellular catabolism are inherently hard to degrade. I suggested a radically new approach: augmenting humans' natural catabolic machinery with microbial enzymes. Many recalcitrant organic molecules are naturally degraded in the soil. Since the soil in certain environments -- graveyards, for example -- is enriched in human remains but does not accumulate these substances, it presumably harbours microbes that degrade them. The enzymes responsible could be identified and engineered to metabolise these substances in vivo. At this meeting we surveyed a range of such substances, their putative roles in age-related diseases and the possible benefits of their removal. We discussed how microbes capable of degrading them can be isolated, characterised and their relevant enzymes engineered for this purpose, and ways to avoid potential side-effects.

In order to address this wide range of topics as knowledgeably as possible, the participants in this roundtable comprised leading experts in all the relevant areas. The participants and their fields of expertise were:

Aubrey de Grey - Chair
Pedro Alvarez - Bioremediation
Perry McCarty - Bioremediation
Bruce Rittmann - Bioremediation
Jay Jerome - Lysosomal dysfunction in atherosclerosis
Ralph Nixon - Lysosomal dysfunction in neurodegeneration
Janet Sparrow - Lysosomal dysfunction in age-related macular degeneration
Ana Maria Cuervo - Targeting intracellularly-synthesised proteins to lysosomes
Roscoe Brady - Targeting exogenously-synthesised proteins to lysosomes