Sn-2 palmitate-enriched structured lipids attenuate early aging phenotypes in senescence-accelerated mice

Aging is characterized by progressive cognitive decline and metabolic dysregulation, contributing to increased vulnerability to age-related disorders. β-position palmitic acid -containing structured lipids (sn-2 palmitate), naturally enriched in human milk fat, have been reported to modulate inflammation and lipid metabolism. However, whether sn-2 palmitate-rich lipids exert beneficial effects beyond early development, particularly in the context of aging-related decline, remains unclear; further, its effects in aged populations or senescence models remain largely unknown. Therefore, we investigated the potential anti-aging effects of sn-2 palmitate-enriched lipid in senescence-accelerated mouse prone 8 (SAMP8)-a model of age-related functional decline. Eight-week-old SAMP8 mice were fed a sn-2 palmitate-enriched lipid supplemented diet for eight weeks. Behavioral tests, hippocampal biochemical analyses, and histological assessments were performed. sn-2 palmitate-enriched lipid supplementation significantly improved cognitive performance and reduced hippocampal expression of senescence markers (p16, p21) and pro-inflammatory cytokines (IL-6, TNF-α). Furthermore, sn-2 palmitate enhanced NAD⁺/NADH ratios and increased Sirt1/3 deacetylase activities, accompanied by upregulation of mitochondrial biogenesis-related factors (PGC-1α, NRF1, TFAM). These findings suggest that sn-2 palmitate-enriched lipid may attenuate aging-associated cognitive and physiological decline through modulation of NAD⁺ metabolism and mitochondrial function.