Fig. 5

tert^-/- mutants accelerate the onset of age-associated cachexia and neoplasia.tert-/- mutants accelerate the onset of age-associated cachexia and neoplasia.A) Representative images of WT and tert^-/- mutants show that, at time-of-death (TOD), zebrafish exhibit signs of cachexia and deformation of the spine, with very low body mass indexes. B) In WT population the incidence of these alterations increases with age, while in tert^-/- mutants, at TOD, 100% of the population is affected. C) Sustained cachexia in older zebrafish is accompanied by an increase in mortality as shown by Kaplan Meier curves of WT and tert^-/- zebrafish. WT zebrafish have a half-life of 30.8m, 3x greater than the half-life of 10.6m of tert^-/- (p<0.0001). N = 426 WT; N = 98 tert^-/-, for Fig 5A–5C. TOD corresponds to the interval comprising the second and third quartiles of survival (25 to 75%). Scale bar = 1 cm. D) Tumorigenesis exponentially accelerates with age in both WT and tert^-/- zebrafish, reaching cumulative incidences of ca. 10% and ca. 8%, respectively. N = 23/238 WT; N = 5/66 tert^-/-. tert^-/- mutants have an earlier onset of neoplasia starting at 4 months of age (p = 0.003). E) Tumors in WT male zebrafish affect mainly the reproductive system, following the appearance of Periodic Acid Shift (PAS+) stained cells in the tissue stroma (F), (quantified in G). WT females show an even distribution of tumors between reproductive and hematopoietic systems, followed by liver, intestine and pancreas. N = 118 WT males; N = 120 WT females; N = 58 tert^-/- males; N = 8 tert^-/- females. Quantifications of %PAS+ cells was performed in 3 fields of view for each individual in the graph. Scale bar = 50 µm. Data are represented as mean +/- SEM.