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Evidence for Biological Age Acceleration and Telomere Shortening in COVID-19 Survivors.

ABSTRACT: The SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokine release, and immunosuppression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called persistent post-COVID-19 syndrome (PPCS) is a common finding. In COVID-19 survivors, PPCS presents one or more symptoms: fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. In this study, a cohort of 117 COVID-19 survivors (post-COVID-19) and 144 non-infected volunteers (COVID-19-free) was analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. The results show a consistent biological age increase in the post-COVID-19 population, determining a DeltaAge acceleration of 10.45 ± 7.29 years (+5.25 years above the range of normality) compared with 3.68 ± 8.17 years for the COVID-19-free population (p < 0.0001). A significant telomere shortening parallels this finding in the post-COVID-19 cohort compared with COVID-19-free subjects (p < 0.0001). Additionally, ACE2 expression was decreased in post-COVID-19 patients, compared with the COVID-19-free population, while DPP-4 did not change. In light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID-19 condition, particularly in younger patients (< 60 years).

SUBMITTER: Mongelli A

PROVIDER: S-EPMC8201243 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundOocytes may undergo two types of aging. The first is induced by exposure to an aged ovarian microenvironment before being ovulated, known as 'reproductive or maternal aging', and the second by either a prolonged stay in the oviduct before fertilization or in vitro aging prior to insemination, known as 'postovulatory aging'. However, the molecular mechanisms underlying these aging processes remain to be elucidated. As telomere shortening in cultured somatic cells triggers replicative senescence, telomere shortening in oocytes during reproductive and postovulatory aging may predict developmental competence. This study aimed to ascertain the mechanisms underlying altered telomere biology in mouse oocytes during reproductive and postovulatory aging.MethodsWe studied Tert expression patterns, telomerase activity, cytosolic reactive oxygen species (ROS) production, and telomere length in fresh oocytes from young versus reproductively-aged female mice retrieved from oviducts at 14 h post-human chorionic gonadotropin (hCG), in vivo or in vitro postovulatory-aged mouse oocytes at 23 h post-hCG. Oocytes were collected from super-ovulated C57BL/6 J mice of 6-8 weeks or 42-48 weeks of age. mRNA and protein expressions of the Tert gene were quantified using real-time quantitative reverse transcriptase polymerase chain reaction (Q-PCR) and immunochemistry. Telomerase activity was measured by a telomeric repeat amplification protocol assay, while telomere length was measured by Q-PCR and quantitative fluorescence in situ hybridization analyses.ResultsThe abundance of Tert expression in oocytes significantly decreased during reproductive and postovulatory aging. Immunofluorescent staining clearly demonstrated an altered pattern and intensity of TERT protein expression in oocytes during reproductive aging. Furthermore, relative telomerase activity (RTA) in oocytes from reproductively-aged females was significantly lower than that in oocytes from young females. In contrast, RTA in postovulatory-aged oocytes was similar to that in fresh oocytes. Oocytes from reproductively-aged females and postovulatory-aged oocytes showed higher ROS levels than oocytes from young females. Relative telomere length (RTL) was remarkably shorter in oocytes from reproductively-aged females compared to oocytes from young females. However, postovulatory aging had no significant effect on RTL of oocytes.ConclusionsLong-term adverse effects of low telomerase activity and increased ROS exposure are likely associated with telomere shortening in oocytes from reproductively-aged female mice.

Project description:In an epidemic, it is important to have methods for reliable and rapid assessment of risk groups for severe forms of the disease for their priority vaccination and for the application of preventive lockdown measures. The aim of this study was to investigate risk factors for severe forms of COVID-19 in adults using indicators of biological and subjective aging. Longitudinal studies evaluated the severity of the disease and the number of cases. Respondents (447) were divided into "working group" and "risk group" (retirees with chronic diseases). During the lockdown period (in mid-2020), accelerated aging was observed in the group of workers (by 3.9-8 years for men and an increase at the tendency level for women). However, the respondents began to feel subjectively younger (by 3.3-7.2 years). In the risk group, there were no deviations from the expected biopsychological aging. The number of cases at the end of 2020 was 31% in workers and 0% in the risk group. Reasonably, the risk group followed the quarantine rules more strictly by 1.5 times. In working men, indicators of relative biological and relative subjective aging (measured in both 2019 and mid-2020) significantly influenced the incidence at the end of 2020. In women, only the indicators obtained in mid-2020 had a significant impact. The relative biological aging of an individual tested in the middle of 2020 had a direct impact on the risk of infection (p < 0.05) and on the probability of death (p < 0.0001). On the contrary, an increase in the relative subjective (psychological) aging index reduced the risk of infection (at the tendency level, p = 0.06) and the risk of death (p < 0.0001). Both the risk of infection and the risk of death increased with calendar age at the tendency level. Conclusions: Indicators of individual relative biological and subjective aging affect the probability of getting COVID-19 and its severity. The combination of high indicators of biological aging and underestimated indicators of subjective aging is associated with increased chances of developing severe forms of the disease.

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Evidence for Biological Age Acceleration and Telomere Shortening in COVID-19 Survivors.

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