Accelerated biological aging in COVID-19 patients

Abstract

Chronological age is a risk factor for SARS-CoV-2 infection and severe COVID-19. Previous findings indicate that epigenetic age could be altered in viral infection. However, the epigenetic aging in COVID-19 has not been well studied. In this study, DNA methylation of the blood samples from 232 healthy individuals and 413 COVID-19 patients is profiled using EPIC methylation array. Epigenetic ages of each individual are determined by applying epigenetic clocks and telomere length estimator to the methylation profile of the individual. Epigenetic age acceleration is calculated and compared between groups. We observe strong correlations between the epigenetic clocks and individual’s chronological age (r > 0.8, p < 0.0001). We also find the increasing acceleration of epigenetic aging and telomere attrition in the sequential blood samples from healthy individuals and infected patients developing non-severe and severe COVID-19. In addition, the longitudinal DNA methylation profiling analysis find that the accumulation of epigenetic aging from COVID-19 syndrome could be partly reversed at late clinic phases in some patients. In conclusion, accelerated epigenetic aging is associated with the risk of SARS-CoV-2 infection and developing severe COVID-19. In addition, the accumulation of epigenetic aging from COVID-19 may contribute to the post-COVID-19 syndrome among survivors.

Biological age is increased by stress and restored upon recovery

“…36 Not only are the elderly up to 90-fold more vulnerable to death from COVID-19, 37 but we and others have previously reported that accelerated biological age is associated with incidence and severity of COVID-19. [38][39][40][41][42] Longitudinal biological age data covering the COVID-19 disease course is also extremely limited.…”

A cautionary note on altered pace of aging in the COVID-19 era

“…Recently, a Spanish study by Cao et al 2022 [24] reported significant acceleration of epigenetic aging using Hannum [7] , PhenoAge [56] , skin Horvath and GrimAge [55] clocks and DNAm TL [16] attrition acceleration in young (>50 y) and old (>50 y) COVID-19 patients compared with healthy individuals. Using the Bernarde et al’s [57] longitudinal cohort, they found that DNAm ages calculated from five clocks and TLs of the samples collected sequentially during the disease process of six patients showed an acceleration of epigenetic aging in the Hovarth age, PhenoAge and GrimAge at the initial phases of COVID-19, and the accumulation of age acceleration was incompletely reversed at later phases of convalescence in certain individuals.…”

“…Because the systematic evaluation of DNA methylation signature of COVID-19 in relation to the biological age is currently a new scientific inquiry [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , this correspondence is organized around three overarching medico-legal concerns that need to be addressed for understanding the influence of COVID-19 on forensic age estimation in survivors. These concerns include: (1) the possibilities of biological and/or epigenetic age acceleration [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , TL attrition [17] , [24] , [35] , [36] , and altered thymic function with its closely related marker (sjTrec) that may be involved in the pathogenesis of COVID-19 [30] , [31] , [32] , [33] , [34] ; (2) the presence of population differences in both vulnerability and the outcome of the infection such as mortality and long COVID syndrome which has ramifications on the precision of age estimates by the forensic models [37] , [38] , [39] , [40] , [41] ; (3) the protective effect exerted by mRNA vaccines and drugs like metformin, rapamycin, and anti-androgens as potential lifespan-extending against COVID-19 and subsequently the deceleration of epigenetic age [21] , [42] , [43] .…”

“…There is an abundance of clinical and epigenetic studies that highlighted the association between the viral life cycle of HIV [48] as well as different types of coronavirus, including SARS-CoV-2 and the molecular mechanisms linked to the host immune response to viral infections [48] , [49] , [50] , [51] , [52] , [53] . The findings of several studies showed significant differential DNA methylation pattern in brain [29] and blood samples associated in COVID-19 patients [22] , [23] , [24] , [27] , [28] , [29] . The comparative DNA methylation profiling of severe COVID-19 revealed an altered genome-wide methylome signature at 44 CpG sites denoted as the epigenetic susceptibility loci for respiratory failure cases [28] .…”

“…SARS-CoV-2, as an RNA virus, is capable of hijacking the epigenetic landscape of host immune cells to suppress the host antiviral response [22] , [30] , [49] , [50] , [51] . These epigenetic mechanisms are closely linked to the control of lymphopoiesis and the immune response depending on the disease severity [22] , [23] , [24] , [27] , [28] , [50] , [57] . Therefore, obvious cell-type shifts in the composition of blood cell have been correlated with the severity of COVID-19 disease due to the effect of COVID-19 DNAm signature.…”