Extended Data Figure 1: Muscles of geriatric and progeric mice show signs of sarcopenia and present defective regeneration.

a, Representative images of haematoxylin and eosin (H/E) stained cryosections of tibialis anterior muscle from wild-type mice at different ages: young (2–3 months), adult (5–6 months), old (20–24 months) and geriatric (28–32 months) mice. Asterisks indicate atrophic myofibres. Arrows indicate central-nucleated myofibres. Histograms represent the quantification of myofibre size, evaluated by the cross-sectional area. Frequency distribution of fibres according to size from tibialis anterior muscles from wild-type mice at different ages, and grip strength corrected for body weight. b, Representative pictures of NCAM immunostained cryosections of tibialis anterior muscle from old and geriatric mice. c, As in panel b. Representative pictures of eMHC immunostaining. Histogram represents the quantification of the number of eMHC-positive myofibres per section. d, Fibre-type distribution and quantification of myofibre size, evaluated by the cross-sectional area of the fibres. Quantifications were performed in cryosections stained for specific MHC antibodies. e, Representative images of haematoxylin and eosin staining in cryosections of tibialis anterior muscle from 12-month-old SAMP8 and SAMR1 mice. Asterisks indicate atrophic myofibres. f, Representative images of eMHC staining in cryosections of regenerating tibialis anterior muscle from adult, old and geriatric mice 1 week after cardiotoxin (CTX)-induced injury. Histograms represent the quantification of the number of eMHC⁺ myofibres and myofibre size, evaluated by the cross-sectional area. g, Immunostaining for dystrophin and nuclear labelling with DAPI was performed in cryosections of extensor digitorum longus muscle from adult and geriatric mice, and SAMR1 and SAMP8 mice 1 week after heterografting onto the tibialis anterior muscle of young mice, and numbers of DAPI-stained nuclei within the dystrophin-positive sarcolemma were quantified. h, Equal numbers of FACS-purified satellite cells from adult, old and geriatric mice, labelled with a lentivirus expressing GFP, were transplanted into the tibialis anterior muscle of young (3 months old) immunodeficient mice. Seven days after transplantation, muscles were collected, sectioned and immunostained for GFP (green). Representative images of transplanted muscles are shown. Graph showing total numbers of GFP⁺ myofibres scored per muscle. i, Equal numbers of purified satellite cells from SAMP8 and SAMR1 mice were labelled and transplanted into muscles of young immunodeficient mice, and analysed as in panel h. Scale bars, 50 μm. Data are mean ± s.e.m. Two-sided Mann–Whitney U-test was used to assess statistical significance. P values are indicated. a, c, n = 10 mice; d, n = 4 mice; f–i, n = 5 donor mice. f, g, Two muscles grafted per donor mouse. h, i, At least three independent engraftments per donor mouse. n.s., not significant.