Inflammaging? Blame T cells!: Mitochondrial dysfunction in various tissues is a prominent characteristic of age-related deterioration, but it is unclear how mitochondrial dysfunction in particular cell types contributes to this process. Desdín-Micó et al. generated mice with T cells that were specifically deficient in a mitochondrial DNA–stabilizing protein. These animals exhibited multiple features associated with aging, including neurological, metabolic, muscular, and cardiovascular impairments. The defective T cells initiated an inflammatory program similar to that observed in older animals, a process called “inflammaging.” Blocking the cytokine tumor necrosis factor–α or administering precursors of the cofactor nicotinamide adenine dinucleotide restored many of these symptoms of senescence. These findings may potentially inform future therapies for age-associated diseases, as well as cachexia and cytokine-release syndrome. Science , this issue p. 1371

Shivering Viromes: Despite its icy reputation, freshwater ponds and lakes do occur in Antarctica, and open freshwater can be found for a few brief weeks during the austral summer. The ecology of these lakes is, as expected, rather specialized to cope with the extreme seasonal conditions. In a metagenomic study, López-Bueno et al. (p. 858 ) inspected the virus community of Lake Limnopolar on Livingston Island and found an unexpectedly rich genetic diversity. A dominant group of previously unidentified single-stranded DNA viruses was found, and a striking shift after ice-melt in spring from single-stranded to double-stranded DNA viruses was observed, probably as their algal hosts started to bloom with increasing daylight hours. The diverse viruses may donate specialized genes that host organisms can also exploit to aid their survival under winter extremes of heat and light deprivation.

Antiviral strategies to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here, we demonstrate that the NRF2 antioxidant gene expression pathway is suppressed in biopsies obtained from COVID-19 patients. Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a cellular antiviral program that potently inhibits replication of SARS-CoV2 across cell lines. The inhibitory effect of 4-OI and DMF extends to the replication of several other pathogenic viruses including Herpes Simplex Virus-1 and-2, Vaccinia virus, and Zika virus through a type I interferon (IFN)-independent mechanism. In addition, 4-OI and DMF limit host inflammatory responses to SARS-CoV2 infection associated with airway COVID-19 pathology. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and in suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2.