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ABSTRACT: In both humans and animals there is a progressive loss of muscle strength with age. Tests of handgrip and knee extension in men show that some decline in strength is evident by the age of 55 years and is pronounced by the age of 65, compared with the 25- to 35-year period when strength is at a maximum. A comparable age-related decline in peak force development has also been shown in hindlimb muscles of aged rats. Motoneurons and consequently motor units are lost with age, and this is apparent in man after the age of 60. Again, a comparable decline has been demonstrated in the motoneuron population of hindlimb muscles of rats aged 20-24 months. Loss of motoneurons in young adults (through either injury or disease) results in the remaining intact motoneurons sprouting to innervate the denervated fibers. This capacity for sprouting has been shown to be seriously impaired in the hindlimb muscles of aged rats. Furthermore, the well-established relationship between motor unit size and fatigability (smaller units tend to be more fatigue resistant) also tends to break down, with large units just as likely to be fatigable as fatigue resistant. The normally large, fatigable motor units also appear to be reduced in size in the aged muscles. The age-related loss of motoneurons and associated loss of muscle fibers accounts in part for the reduced functional capacity of muscle with age. The reason for the impairment of the aged motoneuron remains to be investigated, but it may relate to the integrity of the oxidative metabolic pathways within the cell, given that mitochondrial respiratory chain function is known to be reduced with age.