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PloS One 9 , e100002 (2014)

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This represents one of the strongest genetic validations of an aging target Centenarian correlation: Serum beclin-1 levels above 1.5 ng/mL are associated with 3.4-fold increased odds of being a healthy centenarian, providing human correlative evidence for the pathway Viral protection: Tat-Beclin-1 reduced mortality from chikungunya, West Nile, and other viral infections in mice Aggregate clearance: Treatment reduced polyglutamine aggregate accumulation in cellular models, relevant to proteostasis and neurodegenerative disease Broader autophagy literature: Autophagy enhancement extends lifespan in yeast, worms, flies, and mice across multiple genetic and pharmacological approaches, providing robust cross-species validation Evidence Quality Assessment# Tat-Beclin-1 has the edge in evidence quality for two reasons: (1) the genetic lifespan data from F121A mice provides the gold-standard target validation (proving that constitutive disruption of the beclin 1-BCL2 interaction extends life), and (2) the human centenarian data adds a translational correlation that FOXO4-DRI lacks