Embrace the fat when getting old

by a gradual loss of physiological homeostasis, from the cellular to the organismic level, with ultimately fatal consequences. A more systemic understanding of the cell types and pathways at play is required for rational, targeted interventions into this progressing process [1]. Aging is a normal part of human life-span on the one hand, but associated with many disease risks on the other, indeed, the deterioration frequently exhibited during aging is considered a major risk factor for many human pathologies including type II diabetes mellitus and obesity. Immuno-metabolic derailments accompany the aging process and the development of obesity. Both phenomena therefore share many biological similarities including inflammatory insults and multi-layered cellular and subcellular aberrations [2]. Examples include altered intercellular communication, mitochondrial dysfunction and deregulated nutrient sensing; all hallmarks of aging that are also characteristic in the context of obesity. Among the other hallmarks of aging are stem cell exhaustion, loss of proteostasis, and cellular senescence [3]. The clearance of accumulating damaged cells or senescent cells through phagocytosis is a common strategy to counteract these harmful effects, including in the context of the aging process. As such, the immune system has been recently implicated as a central mediator of organ-level homeostasis and can thus help to preserve tissue integrity in anti-aging interventions. However, a fine balance is required to avoid uncontrolled over-activation of such beneficial immune responses, which may predispose to autoimmune consequences. The precise molecular-level characteristics of immune-metabolic interactions, including the involvement of subsets of phagocytes, and ways to specifically recruit and activate them to counteract aging-related metabolic risks and sustain homeostasis, still remain to be identified. Recently, we have discovered a novel subpopulation of lipid-associated macrophage (LAM) cells [4]. By means of massively parallel single-cell RNA-sequencing and computational modelling, we generated a dynamic atlas of murine adipose tissue immune cells during the gradual transition from the lean to the obese state in mice fed a high-fat diet. We observed dominant changes occurring in the myeloid compartment, and identified Trem2, a triggering receptor expressed on myeloid cells, as a major, previously unrecognized driver of Editorial