Aims: The anabolic responses to postabsorptive resistance exercise (RE) are less in older (O) than younger (Y) men. We hypothesized amelioration of this by supplementing a protein drink (Slim-Fast Optima, SFO) with leucine (Leu), taken immediately after RE. Methods: Three groups (n=9) of healthy young (24±6 y, body mass index (BMI) 22±3 kg.m-2) and older men (70±5 y, BMI 23±4 kg.m-2) were randomized to (i) RE alone, (ii) RE followed by 325 ml SFO (10 g protein, 24 g carbohydrate) with 4.2 g of leucine, (ii) RE+SFO with 4.2 g of alanine (Ala), as 8 repetitions full-cycle unilateral leg RE at 75%×control. Subjects performed 6 of 1-Repetition Maximum. Also, a 4th group of older men (70±5 y, BMI 23±4 kg.m-2) ingested SFO+4 g leucine at rest. Muscle biopsies were taken before, immediately after, and 1, 2 and 4 h after RE or SFO. MPS was measured by incorporation of [1, 2-13C2]leucine and the phosphorylation of p70S6K by western analysis. Results: SFO+Leu enhanced (P<0.01) post-RE responses of MPS compared to those post-RE alone: (AUC MPS (% protein/4 h) Y 0.15±0.05 vs. 0.09±0.03; O 0.14±0.05 vs. 0.08±0.02). In older but not younger, SFO+Leu enhanced post-RE P70s6K phosphorylation above that after RE alone (AUC P70s6K (% increase/4 h): O, 0.50±0.23 vs. 0.25±0.28; Y, 0.63±0.36 vs. 0.56±0.40). RE+SFO+Leu stimulated MPS more than resting SFO+Leu in older (AUC: 0.14±0.05 vs. 0.11±0.05). However, responses to RE+SFO+Ala were identical to RE+SFO alone. Conclusion: Combining RE with SFO+leucine rejuvenates the time-averaged responses of MPS in the older men, mimicking responses in young men. Source of research support: UK BBSRC, (BB/X510697/1, and BB/C516779/1), the European Union EXGENESIS program and Unilever plc.