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preliminary work to explore the feasibility of a proposal I had originally
made in 1999 and on which I had published a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.
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“Mankind will postpone human aging substantially in the future, doubling the human lifespan at least, when we have accomplished this we will be ashamed that we did not work on it much sooner..(from the ABCseries 'Future Fantastic'” ref
