Senescent cells (SCs) accumulate with age and after genotoxic stress, such as total-body irradiation (TBI)1–6. Clearance of SCs in a progeroid mouse model using a transgenic approach delays several age-associated disorders7, suggesting that SCs play a causative role in certain age-related pathologies. Thus, a ‘senolytic’ pharmacological agent that can selectively kill SCs holds promise for rejuvenating tissue stem cells and extending health span. To test this idea, we screened a collection of compounds and identified ABT263 (a specific inhibitor of the anti-apoptotic proteins BCL-2 and BCL-xL) as a potent senolytic drug. We show that ABT263 selectively kills SCs in culture in a cell type– and species-independent manner by inducing apoptosis. Oral administration of ABT263 to either sublethally irradiated or normally aged mice effectively depleted SCs, including senescent bone marrow hematopoietic stem cells (HSCs) and senescent muscle stem cells (MuSCs). Notably, this depletion mitigated TBI-induced premature aging of the hematopoietic system and rejuvenated the aged HSCs and MuSCs in normally aged mice. Our results demonstrate that selective clearance of SCs by a pharmacological agent is beneficial in part through its rejuvenation of aged tissue stem cells. Thus, senolytic drugs may represent a new class of radiation mitigators and anti-aging agents.
Toxoplasma gondii has been suggested as an important opportunistic pathogen in immunocompromised patients. We conducted a global meta-analysis to assess the prevalence and odds ratios (ORs) of T. gondii infection in immunocompromised individuals. Electronic databases were reviewed for T. gondii infection in HIV/AIDS patients, cancer patients, and transplant recipients, and meta-analyses were conducted to calculate overall estimated prevalence and ORs using random or fixed-effects models. Totally, 72 eligible studies were included. The estimated pooled prevalence of T. gondii infection in immunocompromised patients and the control was 35.9 and 24.7% (p < 0.001), with an OR of 2.24, i.e., 42.1 and 32.0% for HIV/AIDS patients and the control (p < 0.05), 26.0 and 12.1% for cancer patients and the control (p < 0.001), and 42.1 and 34.5% for transplant recipients and the control (p > 0.05), whose estimated pooled ORs were 1.92 (95% CI, 1.44–2.55), 2.89 (95% CI, 2.36–3.55), and 1.51 (95% CI, 1.16–1.95), respectively. This study is the first to demonstrate that the immunocompromised patients are associated with higher odds of T. gondii infection, and appropriate prevention and control measures are highly recommended for these susceptible populations.
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