A blood sample and muscle biopsies were obtained from 54 elderly subjects. Twenty-seven subjects aged 77 +/- 3 years, had experienced a change in fat free mass (FFM) of +194 +/- 282 g/year (lean body mass maintainers) and 27 subjects aged 78 +/- 3 years, had a change in FFM of -487 +/- 209 g/year (lean body mass losers). Muscle biopsies were also obtained from 10 healthy subjects aged 34 4 years. In muscle, the ratio of mitochondrial DNA (mtDNA) to nuclear DNA (nDNA) and telomere length were assessed and deposition of 4-hydroxy-2-nonenal adducts (4HNE) was visualized by electron microscopy. In FFM maintainers, losers and young controls, the ratio of mtDNA to nDNA was 2.1 (95% confidence intervals (CI), 0.1-31.7), 1.5 (95% CI, 0.2-15.7) and 18.6 (95% CI, 2.8-46.2), respectively. 4HNE deposition was 5.9 (95% CI, 1.5-28), 4.9 (95% CI, 0.9-13) and 3.4 (95% CI, 1.1-4.6) gold particles/mu m(2), respectively. Telomere length, expressed as T/S ratio, was 0.06 (95% CI, 0.01-0.16), 0.06 (95% CI, 0.03-0.27) and 0.34 (95% CI, 0.1-1.34). respectively (p < 0.02 or less for all comparisons between elderly and young subjects). (c) 2008 Elsevier Ireland Ltd. All rights reserved