Hyperactive mTORC1 suppresses autophagy in aged cells, but the signal that keeps mTORC1 on remains unclear. We propose that persistent lysosomal damage, caused by the buildup of oxidized lipids and protein aggregates, activates the Ragulator‑Rag complex and Src family kinases, which maintain mTORC1 activity even when nutrients are scarce. This creates a self‑reinforcing loop: lysosomal damage → mTORC1 activation → TFEB cytoplasmic retention → reduced lysosomal biogenesis → more damage. Because the loop depends on signaling rather than irreversible loss of autophagy proteins, acute lysosomal stabilization should break the cycle and restore flux.

Testable predictions:

• Aged fibroblasts or neurons will show higher lysosomal membrane permeability (measured by galectin‑3 puncta) that correlates with phospho‑S6K levels, a readout of mTORC1 activity [1][2].
• Pharmacological stabilization of lysosomal membranes using the MCOLN1 agonist ML‑SA1 will reduce phospho‑S6K, increase nuclear TFEB, and revive LC3‑II turnover in aged cells without affecting young counterparts [3][4].
• Genetic knockdown of RagA or Src family kinases in aged tissue should mimic the effect of ML‑SA1, decreasing mTORC1 signaling and increasing autophagy flux [5][6].
• Conversely, inducing lysosomal damage with low‑dose LLOMe in young cells will provoke mTORC1 activation and suppress autophagy, reproducing the aged phenotype [7][8].

If these outcomes hold, the data would support a model in which aging cells actively retain a damaged lysosomal state to sustain mTORC1 signaling, thereby limiting autophagic reset. Conversely, failure to observe lysosomal‑dependent mTORC1 regulation would refute the hypothesis and point to alternative upstream drivers.