Duchenne muscular dystrophy (DMD) is characterized by progressive wasting and cycles of regeneration in skeletal muscle. Work from our laboratory (1.), suggests that branched fibres, that form as a consequence of repeated bouts of regeneration, could be responsible for the terminal phase of mechanical muscle damage in old (58-112 weeks) dystrophic mice. A recent study (2.) in adult 12 week old mdx dystrophic mice reported that the majority of force loss produced by a series of eccentric contractions (EC) in extensor digitorium longus (EDL) muscles recovers (65%) within 120 minutes. The authors conclude this is incompatible with the assumption that EC force loss is due to mechanical damage. The majority of studies assess force recovery 10 minutes post EC. Our aim was to assess the recovery post EC damage at up to 120 minutes in old and adult dystrophic muscles. Male mdx mice (C57BL/10) at either 88 weeks or 16 weeks of age were killed with an overdose of isoflurane and fast-twitch EDL muscles dissected from the hind limbs. Each muscle was maintained in Krebs solution with carbogen at room temperature. The muscle was maximally stimulated at 125 Hz and a series of EC were given at 10% (three) and 20% (three) stretch from optimal length (Lo), the muscles were then rested for up to 120 minutes before measuring the recovery. Single muscle fibres were isolated enzymatically using collagenase to assess the degree of fibre branching in 16 week mdx EDL. Table1 shows a small recovery in the old 88 week group and a statistically significant larger recovery in the adult 16 week group. These findings of minimal recovery at 120 minutes post EC force loss in EDL muscles from 88 week mdx dystrophic mice support our “tipping point” hypothesis (1.) that there is a distinct pathophysiology, EC force loss due to acute fibre rupture at branch nodes, which occurs in “aged”(58-112 weeks) dystrophic EDL muscles (>70% complex branched fibres). Our branched fibre “tipping point” hypothesis predicts the reduced membrane damage in the younger dystrophic age group is a consequence of the fact that the number and complexity of regenerated branched fibres has not passed a “tipping point” where branching will mechanically compromise the strength of fibres. These findings have important implications for pre-clinical drug studies which have used protection from EC damage as a marker for drug efficacy, but have only recorded force recovery after 10-20 minutes in young/adult mdx mice.