The Impact of Cysteine on Lifespan in Three Model Organisms: A Systematic Review and Meta-analysis

Cysteine is an amino acid present in thiol proteins and often dictates their secondary structures. Although considered nonessential, cysteine may be essential for patients with certain metabolic diseases and can reduce the requirement for dietary methionine. Cysteine and some of its derivatives, such as N-acetylcysteine, are considered antioxidants and widely used in animal aging studies. To provide insights into the potential anti-aging effects of cysteine, we systematically reviewed and performed a meta-analysis to investigate the impact of cysteine supplementation on lifespan using three model organisms: mice, nematodes, and fruit flies. A total of 13 mouse studies, 13 C. elegans studies, and 5 Drosophila studies were included in the analysis. The findings revealed that cysteine supplementation significantly reduced the risk of mortality in mice and C. elegans. Subgroup analysis showed consistent results across different starting times and administration methods and revealed adverse effects of high doses on worms and a lack of effect in nondisease mouse models. Similar to mice, the effects of cysteine supplementation on Drosophila were not statistically significant, except in transgenic flies. The study identified certain limitations, including the quality of the included studies and the potential for publication bias. We also discussed uncertainties in the underlying molecular mechanisms and the clinical application of dietary cysteine.