Aging is characterized by gradual immune dysfunction and increased risk for many diseases, including respiratory infections. Genomic instability is thought to play a central role in the aging process but the mechanisms that damage nuclear DNA in aging are insufficiently defined. Cells that migrate or reside within confined environments experience forces applied to their nucleus, leading to transient nuclear envelope (NE) ruptures. NE ruptures are associated with DNA damage, and Lamin A/C is required to limit these events. Here, we show that Lamin A/C protects lung alveolar macrophages from NE rupture and hallmarks of aging. Lamin A/C ablation in immune cells results in a selective depletion of lung alveolar macrophages (AM) and a heightened susceptibility to influenza infection. Lamin A/C-deficient AM that persist display constitutive nuclear envelope rupture marks, DNA damage and p53-dependent senescence. In wild-type mice, we found that AM migrate within constricted spaces in vivo, at heights that induce NE rupture and DNA damage. AM from aged wild-type mice and from Lamin A/C-deficient mice share an upregulated lysosomal signature with CD63 expression, and we find that CD63 is required to clear damaged DNA in macrophages. We propose that induction of genomic instability by NE disruption represents a mechanism of aging in alveolar macrophages.
Roads have impacts on the fauna arising from habitat fragmentation, roadkill and the barrier effect. Furthermore, roads lead species to change their activity with repercussions on predator–prey interactions and trigger indirect effects that are currently unknown. This study analyzes the effect of a motorway on the trophic behavior of the terrestrial carnivore community of its surroundings. Monthly scat sampling was conducted over a year at three distances from a motorway (0–50 m, 500–550 m and 1000–1050 m). We collected 498 scats, these originating from red fox (39.16%), cat (24.50%), stone marten (24.09%) and badger (12.25%). The relative abundance of the trophic resources in them was estimated together with the trophic diversity and niche overlap of the carnivore species. The results showed a distinct effect of distance from the road on trophic behavior of carnivores, as well as differences between species and seasons. The scats nearest the road had 10–20% more biomass of small mammals, equivalent in relative terms to a 21–48% increase in small mammals’ biomass when compared with scats collected further from the road. This finding indicates changes in predator–prey interactions near the road and shows that the human-generated structural and functional changes to ecosystems spread throughout trophic networks.
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