09:00 Arrival, introductions

09:20 Stock/de Grey: overview of the 1999 meeting and how this meeting builds on it

09:40 de Grey for Austad: definition of negligible senescence; differences between the physiology and cell biology of negligibly senescent and other vertebrates; progress towards emulating such differences as an approach to regenerative medicine

10:15 Coffee break

10:35 McCarter: physiology of sarcopenia; loss of systemic homeostasis caused by it; proven methods for reversing it; unproven but realistic methods (e.g. satellite cell repopulation)

11:10 Andersen: physiology of neurodegenerative diseases of aging; pharmacological reversal of symptoms; reversal by repopulation of affected cells or precursors; reversal by destruction of extra- and intracellular aggregates

13:00 Bartke: hormonal mechanisms for extension of mammalian lifespan; when they extend it and when they shorten it; options for reversal of aging by hormonal manipulation, including stimulation of cell proliferation; deleterious side-effects and their avoidance

13:35 Campisi: incidence of replicative senescence (or approach to it) in various tissues; mechanisms underlying its pathological significance (cancer, immune decline etc); reversal of its effects by elimination of such cells; reversal by telomerase manipulation

14:30 Ames: accumulation of nuclear mutations; pathological significance (cancer and other); capacity for reversal by cell turnover; role of micronutrients in reducing the level of pre-mutagenic lesions; mechanisms of loss and gain of methylation and other regulatory DNA adducts; interventions to reverse the loss of such regulation

15:05 de Grey: population dynamics of mutant mitochondrial DNA in vivo; mechanisms underlying its pathological effects; reversal of its effects by nuclear complementation and other methods

16:00 de Grey for Cerami: intralysosomal and extracellular cross-linking leading to undegradable aggregates; pathological sigificance; pharmacological means to eliminate or un-link such aggregates, e.g. ALT-711; controversies regarding lipofuscin (centrophenoxine etc); transgenic destruction of lipofuscin and/or its equivalent in arterial macrophages and retina.

16:35 de Grey/Stock: summary of the day’s discussions to this point; tentative prioritisation of the specific projects identified and their relationship to the 1999 milestones.

16:55 Heward: practical challenges and technical obstacles; difficulties involved in translating the meeting’s various projects from the laboratory to the clinic.

17:15 Stock: social/ethical/policy implications in the short and midterm (up to 10 years hence)