Age-related lysosomal and autophagic dysfunction and intra-lysosomal ROS generation in marine mussels

Abstract Mussel cells from three age groups (i.e., 2–4, 5–6, and ≥ 10 years) were tested for lysosomal membrane stability (LMS – membrane permeability and proton pump function), autophagic rate, and intralysosomal reactive oxygen species (ROS). LMS was significantly reduced in haemocytes and digestive cells of the hepatopancreas (digestive gland) in the two older groups of mussels, while autophagy in haemocytes was reduced in the oldest age group. ROS generation was measured in digestive cells and was reduced in the oldest age group. Age-related decline in LMS and autophagy may be related to dysfunction of the PI3P-Akt-mTOR signalling pathway. Lysosomal autophagy can also be a source of ROS generation as the degradation product lipofuscin (age/stress pigment) accumulates in autolysosomes and residual bodies; and lipofuscin-associated iron can generate ROS. Previous investigation found age-related increased lipid peroxidation in digestive gland cells, whereas this study only assessed ROS generation in the lysosomal compartment of digestive cells and may reflect increased lysosomal and autophagic dysfunction. Principal component analysis, multidimensional scaling, and cluster analysis showed that the three age groups were significantly different from each other, with the oldest mussels showing the greatest degree of cellular dysfunction. The anti-oxidative protective role of autophagy and possible links to lysosomal and autophagic dysfunction in ovarian oocytes and fecundity reduction with age are discussed in the context of increased fragility in health of older animals (e.g., digestion, autophagic recycling and repair & innate immunity). Consequently, it is recommended that young mussels should be used in environmental biomonitoring with LMS.