The immune system deteriorates as we age. Regulatory T cells contribute to immunosenescence as they critically mold antigenic CD4+ T cell subsets and maintain immunological homeostasis. Given the role of mitochondrial Transcription Factor A (TFAM) in oxidative stress, cellular senescence, and age-related pathologies, we explored the role of this factor in Regulatory T (Treg) cells. We employed a conditional deletion of FoxP3-specific TFAM to create Regulatory T (Treg) cells lacking mitochondrial TFAM. Using comprehensive single-cell RNA cell technology, we identified how mitochondrial TFAM in Treg cells controls the CD4+ T cell fate and trajectory for a heterologous pool of inflammatory CD4 cytotoxic, CD4 exhausted, and CD4 effector memory T cells, all features of aging. Additionally, our results show how TNF signalling and related cell death pathways exacerbate systemic inflammation, degradation, and acceleration of cell death in mice lacking TFAM. Furthermore, partial TFAM restoration or use of the antioxidative drug resveratrol alleviate the inflammaging cascade. These findings reveal TFAM as a critical regulator of Foxp3 Treg cell activity in sculpting the CD4 heterologous pool and point to TFAM as a possible target for pharmacological manipulation in age-related diseases.

In this commentary, we highlight autophagy's important function, while identifying potential therapeutic targets for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the elderly. Autophagy's decline in the elderly causes increased cell senescence and a dysregulated immune system. As this demographic often faces decreased vaccine-provided immunity, coronavirus disease 2019 treatments must be developed. We discuss a recent study by Acharya et al. (2022) that found that SF2523 induced autophagy, reducing SARS-CoV-2 replication. Furthermore, across varying dosages, SF2523 was shown to have a synergistic effect with remdesivir or MU-UNMC. Consequently, we believe that SF2523, alone or with other anti-virals, is a promising potential therapeutic for preventing SARS-CoV-2-related mortalities.Coronavirus disease 2019 (COVID-19)'s appearance has sparked a global pandemic. When severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged and began to spread worldwide, knowledge of the new virus was limited. Now, roughly two years after the world shut down, leading researchers are still studying the virus and working to develop a vaccine capable of combating the growing number of variants, including Delta, Omicron, BA.2, and Deltacron. One thing has remained clear throughout the emergence of the different variants of COVID-19: the elderly demographic appears to be among the most affected by COVID-19 infection. This potentially links back to autophagy, a critical cellular process, which occurs in response to nutrient deprivation and is important to the degradation and removal of harmful cargo, including damaged cellular materials and viral particles, protecting individuals from disease. 1 The autophagy process declines in the elderly, resulting in increased cell senescence and a deregulated immune system. 2,3 Additionally, this This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.