The possible role for isoprenoids in modulating certain aging-related phenotypes is emphasized by this new work demonstrating that the combination of statins and bisphosphonates appears to mitigate these phenotypes, presumably via blockade of both farnesylation and geranylgeranylation. Farnesyl transferase inhibitors (FTIs) had been reported to have such properties, but those observations were apparently less robust in subsequent studies. Another aging-related phenomenon, accumulation of amyloid-β peptide in the brains of amyloid-depositing transgenic mice, is robustly modulated by statins, yet statins have failed in clinical trials to modulate clinical outcome. The new data suggest that human Alzheimer trials of statins might be revisited: perhaps a clinical trial of statins plus bisphosphonates will reveal efficacy where statins alone have failed.

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