RESEARKA

The curated corpus is dominated by preclinical and mechanistic work, with the overwhelming majority of included studies conducted in cell lines (e.g., Greilberger 2023; Greilberger 2022), rodent models (e.g., An 2021; Takemura 2025; Huang 2025; Iniguez 2022; Iwaniak 2022; Qiu 2025), agricultural species such as pigs (Chen 2019; Sun 2025b; Sun 2025c; Tian 2023), carp (Wu 2021; Wu 2022), laying hens (Tomaszewska 2020; Tomaszewska 2021), and invertebrate or yeast organisms (Su 2019; Alpha-ketoglutarate 2018; Bayliak 2017; Burdyliuk 2017). No large-scale, long-duration randomized controlled trial assessing hard clinical endpoints — such as all-cause mortality, incident cardiovascular events, or cancer incidence — in human adults is represented. Consequently, the headline synthesis cannot draw conclusions about AKG's efficacy for the clinical endpoints most relevant to translational decision-making, and the apparent anti-aging signal described by Demidenko 2021 rests on retrospective DNA methylation data rather than prospective hard-outcome evidence.

Citation Support

• source_1 Greilberger 2023
• source_2 Greilberger 2022
• source_3 Qiu 2025
• source_4 Greilberger 2021
• source_5 Wu 2022