D-allulose attenuates D-galactose-induced cardiac aging rats by preserving mitochondrial function, mitochondrial dynamics, and cardiac apoptosis

Abstract

Cardiac aging is characterized by progressive deterioration of cardiac function, mitochondrial dysfunction, cardiomyocyte apoptosis, and cellular senescence. D-galactose-induced aging is a well-established experimental model that recapitulates these alterations. Although D-allulose, a rare sugar with metabolic benefits, and Inulin, a natural soluble prebiotic fiber, have demonstrated beneficial health effects via antioxidant and metabolic regulatory mechanisms, their cardioprotective effects in D-galactose-induced aging remain incompletely understood. This study investigated whether D-allulose exerts anti-cardiac aging effects through modulation of mitochondrial function, dynamics, and apoptosis in an aging rat model. Twenty male Wistar rats (~4 months old) were assigned to either a control group (CON, n=5) or a D-galactose group (D-gal, 150 mg/kg/day, s.c., n=15) for 8 weeks to induce a cardiac aging phenotype. D-galactose-treated rats were subsequently randomized to receive vehicle (VEH, n=5), oral inulin (positive control, INU, 2.0 g/kg/day, n=5), or D-allulose (DAL, 1.9 g/kg/day, n=5) for 12 weeks. Cardiac function was assessed by echocardiography. Mitochondrial function, dynamics, apoptosis, and senescence-related markers were evaluated in cardiac tissue. D-galactose (VEH group) administration induced a cardiac aging phenotype characterized by impaired cardiac function, mitochondrial depolarization, altered mitochondrial dynamics, increased cellular senescence, and apoptosis. Specifically, these aging rats had reduced fractional shortening (%), increased senescence-associated β-galactosidase (SA-β-gal) activity, decreased the red-to-green fluorescence ratio, increased phosphorylation of dynamin-related protein 1 at serine 616 (p-Drp1Ser616), decreased mitofusin-2 (MFN2), and increased the number of TUNEL-positive cells (Figure 1A-F). Notably, D-allulose treatment markedly attenuated these adverse alterations, with effects comparable to those observed with Inulin (Figure 1A-F). D-allulose and Inulin attenuated D-galactose-induced cardiac aging by preserving mitochondrial function, maintaining mitochondrial dynamics, and reducing apoptosis. These findings support D-allulose as a promising nutritional intervention for age-related cardiac dysfunction.Figure 1