LAUSR

ABSTRACT We tested the hypothesis that hesperidin would reverse age‐related aortic stiffness, perivascular adipose (PVAT) mediated‐arterial stiffening and PVAT advanced glycation end‐products (AGE) accumulation. Aortic pulse wave velocity (aPWV) and intrinsic mechanical stiffness, two measures of arterial stiffness, were assessed in C57BL/6 mice that were young (6 months), old (27–29 months), or old treated with hesperidin for 4 weeks. Old compared with young mice had increased aPWV (444 ± 10 vs. 358 ± 8 cm/s, P < 0.05) and mechanical stiffness (6506 ± 369 vs. 3664 ± 414 kPa, P < 0.05). In old mice hesperidin reduced both aPWV (331 ± 38 cm/s) and mechanical stiffness (4445 ± 667 kPa) to levels not different from young. Aortic segments from old animals cultured with (+) PVAT had greater mechanical stiffness compared to young (+) PVAT (6454 ± 323 vs. 3575 ± 440 kPa, P < 0.05) that was ameliorated in arteries from old hesperidin treated cultured (+) PVAT (2639 ± 258 kPa). Hesperidin also reversed the aging‐related PVAT AGE accumulation (all, P < 0.05). A 4‐week treatment with the AGE inhibitor aminoguanidine reversed both the age‐related increase in aPWV (390 ± 7 cm/s) and mechanical stiffness (3396 ± 1072 kPa), as well as mechanical stiffness in arteries cultured (+) PVAT (3292 ± 716 kPa) (all, P < 0.05) to values not different from young. In conclusion, hesperidin ameliorates the age‐related increase in aortic stiffness and the PVAT‐mediated effects on arterial stiffening. Hesperidin also reversed PVAT AGE accumulation, where PVAT AGE were shown to promote aortic stiffness with aging. HIGHLIGHTSAging‐related aortic stiffness is reversed with a dietary hesperidin intervention.Aging increases advanced glycation end‐products (AGE) in perivascular adipose.Hesperidin reduces the aging‐induced perivascular adipose AGE accumulation.AGE inhibition reduces perivascular adipose‐related arterial stiffness with aging.