Thin fiber muscle afferents (group III/IV) signal the sensations of muscle ache and fatigue. Aging may influence the sensitivity of these afferents. However, little is known about mechanisms and receptors involved in this age-related impact. Seventeen young (27±3 years) and thirteen old (68±5 years) matched (sex, BMI, and activity) healthy adults participated in this study. During a first session, participants were familiarized with a twodimensional (2D) scale adapted from the Gracely Box Scale. In a second session, participants received 3 intramuscular (left abductor pollicis brevis) infusions (each 2 mL over 5 minutes) of combinations of metabolites: 1) pH=7.4, ATP=300nmol, lactate=1mmol -found in resting muscle (neutral concentration mixture), 2) pH=7.0, ATP=1μmol, lactate=15mmol -found during moderate exercise (low concentration mixture), and 3) pH=6.6, ATP=5μmol and lactate=50mmol -found during strenuous exercise (high concentration mixture). ATP activates P2X receptors, hydrogen ions (i.e., lowered pH) activate ASIC and TRPV1 receptors, and lactate enhances ASIC activation. These three metabolites act synergistically to activate group III/IV neurons. During the infusion, participants continuously rated their sensations of fatigue and ache on the 2D scale. Young participants reported significantly more fatigue and ache than the older adults with higher fatigue sensations during the infusion of both the low and high concentration mixture (both p<0.05) and more ache during the infusion of the high concentration mixture (p<0.05). In conclusion, although the combined activation of P2X, ASIC, and TRPV1 receptors causes sensations of muscle ache and fatigue in humans, healthy aging decreases the sensations signaled by these molecular receptors. The current findings cannot distinguish whether aging attenuates the excitability/sensitivity of these molecular receptors or alters the central processing of ache and fatigue. Interestingly, the present data contradict previous findings suggesting that sensitized muscle afferents underlie the higher prevalence of muscle fatigue and ache in older individuals.