The crucial impact of lysosomes in aging and longevity

Abstract

Lysosomes are the main catabolic organelles of a cell and play a pivotal role in a plethora of cellular processes, including responses to nutrient availability and composition, stress resistance, programmed cell death, plasma membrane repair, development, and cell differentiation. In line with this pleiotropic importance for cellular and organismal life and death, lysosomal dysfunction is associated with many age-related pathologies like Parkinson’s and Alzheimer’s disease, as well as with a decline in lifespan. Conversely, targeting lysosomal functional capacity is emerging as a means to promote longevity. Here, we analyze the current knowledge on the prominent influence of lysosomes on aging-related processes, such as their executory and regulatory roles during general and selective macroautophagy, or their storage capacity for amino acids and ions. In addition, we review and discuss the roles of lysosomes as active players in the mechanisms underlying known lifespan-extending interventions like, for example, spermidine or rapamycin administration. In conclusion, this review aims at critically examining the nature and pliability of the different layers, in which lysosomes are involved as a control hub for aging and longevity.

Excessive dietary lipid intake provokes an acquired form of lysosomal lipid storage disease in the kidney

“…These structures reached a maximum diameter of 8–9 μm and ultrastructurally resembled the multilamellar bodies (MLBs) that we and others found in kidneys from mice with lysosomal storage diseases such as Fabry and Niemann–Pick type C (NPC1) (supplementary material, Figure S2A). In line with studies associating ageing with lysosomal impairment , aged mice also presented MLBs. As for WD feeding, subjecting mice to a high‐fat diet (HFD) resulted in MLB formation in PTECs (supplementary material, Figure S2A).…”

A lysosome‐plasma membrane‐sphingolipid axis linking lysosomal storage to cell growth arrest

“…Although lysosomes have been mainly considered inert catabolic organelles, it is now clear that they are also crucial regulators of cell homeostasis (4). Lysosomal accumulation of uncatabolized material is a hallmark of a large number of diseases, including lysosomal storage disorders, Alzheimer's disease, Parkinson's disease, and brain aging (5)(6)(7). Moreover, it has been recently demonstrated that diverse lysosomotropic drugs accumulate within the lysosomes, affecting their function (8,9).…”

A physicochemical roadmap of yeast replicative aging

“…The importance of pH homeostasis in aging is also apparent in humans. Human senescent cells show increased lysosomal content and increased lysosomal pH, and in age-related pathologies such as Alzheimer's and Parkinson's disease, lysosomes are dysfunctional 15 . V-ATPases are highly conserved, and Pma1 shares structural and functional similarities with the Na + K + ATPases in mammalian cells [16][17][18] .…”