Comprehensive study of W06A7.4 and TMEM144 mediated pathways in aging: insights from Caenorhabditis elegans to human

Aging is a major biological process underlying increased risk of chronic and neurodegenerative diseases, yet its molecular mechanisms remain incompletely defined. Our study systematically investigates the conserved functions and pathways of W06A7.4 in Caenorhabditis elegans and its human homolog TMEM144 in the regulation of aging, combining genetic manipulation in model organisms, analysis of human clinical samples, and functional assays in cell lines. The results demonstrate that W06A7.4 promotes longevity in C. elegans through synergistic effects with dietary restriction, reduction of oxidative damage, modulation of IIS and mTOR signaling, and maintenance of mitochondrial membrane potential. In human samples and cellular models, TMEM144 expression increases with age and in Alzheimer's disease. Our results suggest that TMEM144 may be involved in the regulation of glucose transport and mitochondrial respiration via the downstream protein TIMMDC1. These findings advance our understanding of evolutionarily conserved aging pathways and identify W06A7.4/TMEM144 as promising molecular targets for anti-aging and neurodegenerative disease interventions.