Heterozygous mutant zebrafish with increased SA-β-gal activity and elevated levels of aging biomarkers in adults.
(A) The heterozygous nrsm/+ mutants showed significantly increased SA-β-gal activity in the skin compared with their wild-type siblings at 3.3 y, but not before 2.1 y (right side graph). Two psm mutants (psm6 and psm9) also showed significantly increased SA-β-gal activity in the skin as heterozygotes, compared with their wild-type sibling counterparts at just 1.5 y (left side graph). *P<0.05; **P<0.01 (Student t-test). (B–G) Shown here are liver sections from a 1.5 y psm7m/+ heterozygote and a wild-type sibling (E and B, respectively), and a 1.5 y psm6m/+ heterozygote and a wild-type sibling (F and C, respectively). All of the heterozygous male psm6m/+ (n = 8) and psm7m/+ (n = 6) mutants analyzed show increased lipofuscin accrual in the liver. Representative liver sections from a 2.1 y nrsm/+ heterozygote and a wild-type sibling are also shown (G and D, respectively) (n = 5 for each). (H) Heterozygous aged nrsm/+ mutants show increased lipofuscin accrual in the skeletal muscle (n = 8 for mutants; n = 5 for wild-type siblings). Longitudinal trunk muscle sections from a 33-month (2.8 y) nrsm/+ heterozygote mutant and a wild-type sibling are shown (left and right panels, respectively), with enlarged images included as insets. (I) Heterozygous and older (23-month old) terf2m/+ mutants show a decreased thickness of the retina, particularly in the photoreceptor layer and inner plexiform layer, compared with age-matched wild-type siblings. Heterozygous older (23-month old) terf2m/+ mutants show increased drusen-like accruals (yellow arrows) with autofluorescence surrounding the RPE area and both more and larger empty space(s) (red arrow) in the inner nuclear layer when compared with an age-matched wild-type sibling. (Scale bar: 100 μm.)
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