SENS roundtable 4: Enhancing lysosomal catabolic function using microbial enzymes
Bethesda, MD, USA, 26th July 2004
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explore the feasibility of a proposal I had originally made in 1999 and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 list of participants was:
| Aubrey de Grey | Chair |
| Pedro Alvarez, Perry McCarty, 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 |
A manuscript arising from the meeting has been published. See here for related articles by me.