Proteostasis and Autophagy in Immune Senescence

Healthcare challenges are intensifying as our population ages. Age is the biggest single risk factor for many debilitating diseases, from infections to cancer. Immune aging contributes by preventing useful immune responses, but this process is little studied. Autophagy, a pathway activated when cells are stressed, clears away debris accumulated over time, recycling building blocks for re-use. Declining autophagy underpins aging in many tissues, especially, as we have shown, in the immune system. We now want to identify what is degraded and what is generated by autophagy, to better understand how it prevents aging. We will study how autophagy controls the amino acid pool and cellular energy levels. While protein synthesis levels decline with age, we recently found that increasing the synthesis of autophagy proteins alone rejuvenates immune cells. By studying this pathway, we hope to identify new ways to prevent or even reverse the aging of our immune cells.