The aim of this study was to identify the most reliable biomarkers in the literature that could be used as flare predictors in systemic lupus erythematosus (SLE). A systematic review of the literature was performed using two databases (MEDLINE and EMBASE) through April 2015 and congress abstracts from the American College of Rheumatology and the European League Against Rheumatism were reviewed from 2010 to 2014. Two independent reviewers screened titles and abstracts and analysed selected papers in detail, using a specific questionnaire. Reports addressing the relationships between one or more defined biological test(s) and the occurrence of disease exacerbation were included in the systematic review. From all of the databases, 4668 records were retrieved, of which 69 studies or congress abstracts were selected for the systematic review. The performance of seven types of biomarkers performed routinely in clinical practice and nine types of novel biological markers was evaluated. Despite some encouraging results for anti-double-stranded DNA antibodies, anti-C1q antibodies, B-lymphocyte stimulator and tumour necrosis factor-like weak inducer of apoptosis, none of the biomarkers stood out from the others as a potential gold standard for flare prediction. The results were heterogeneous, and a lack of standardized data prevented us from identifying a powerful biomarker. No powerful conclusions could be drawn from this systematic review due to a lack of standardized data. Efforts should be undertaken to optimize future research on potential SLE biomarkers to develop validated candidates. Thus, we propose a standardized pattern for future studies.

Aging is characterized by an extensive remodeling of epigenetic patterns, which has been implicated in the physiopathology of age-related diseases. Nutrition plays a significant role in modulating the epigenome, and a growing amount of data indicate that dietary changes can modify the epigenetic marks associated with aging. In this review, we will assess the current advances in the relationship between caloric restriction, a proven anti-aging intervention, and epigenetic signatures of aging. We will specifically discuss the impact of caloric restriction on epigenetic regulation and how some of the favorable effects of caloric restriction on lifespan and healthspan could be mediated by epigenetic modifications.

Tregs are impaired in human systemic lupus erythematosus (SLE) and contribute to effector T cell activation. However, the mechanisms responsible for the Treg deficiency in SLE remain unclear. We hypothesized that the OX40L/OX40 axis is implicated in Treg and regulatory follicular helper T (Tfr) cell dysfunction in human SLE. OX40L/OX40 axis engagement on Tregs and Tfr cells not only specifically impaired their ability to regulate effector T cell proliferation, but also their ability to suppress T follicular helper (Tfh) cell–dependent B cell activation and immunoglobulin secretion. Antigen-presenting cells from patients with active SLE mediated Treg dysfunction in an OX40L-dependent manner, and OX40L-expressing cells colocalized with Foxp3 ⁺ cells in active SLE skin lesions. Engagement of the OX40L/OX40 axis resulted in Foxp3 downregulation in Tregs, and expression in SLE Tregs correlated with the proportion of circulating OX40L-expressing myeloid DCs. These data support that OX40L/OX40 signals are implicated in Treg dysfunction in human SLE. Thus, blocking the OX40L/OX40 axis appears to be a promising therapeutic strategy.

Down syndrome is the most common chromosomal disorder, associated with moderate to severe intellectual disability. While life expectancy of Down syndrome population has greatly increased over the last decades, mortality rates are still high and subjects are facing prematurely a phenomenon of atypical and accelerated aging. The presence of an immune impairment in Down syndrome subjects is suggested for a long time by the existence of an increased incidence of infections, the incomplete efficacy of vaccinations, and a high prevalence of autoimmunity. Immunologic abnormalities have been described since many years in this population, both from a numerical and a functional points of view, and these abnormalities can mirror the ones observed during normal aging. In this review, we summarize our knowledge on immunologic disturbances commonly observed in subjects with Down syndrome, and in innate and adaptive immunity, as well as regarding chronic inflammation. We then discuss the role of accelerated aging in these observed abnormalities and finally review the potential age-associated molecular and cellular mechanisms involved.

Down syndrome (DS) has been proposed by George Martin as a segmental progeroid syndrome since 1978. In fact, DS persons suffer from several age‐associated disorders much earlier than euploid persons. Furthermore, a series of recent studies have found that DS persons display elevated levels of age biomarkers, thus supporting the notion that DS is a progeroid trait. Nowadays, due to the progressive advancements in social inclusion processes and medical assistance, DS persons live much longer than in the past; therefore, the early‐onset health problems of these persons are becoming an urgent and largely unmet social and medical burden. In particular, the most important ailment of DS persons is the accelerated cognitive decline that starts when they reach about 40 years of age. This decline can be at least in part counteracted by multi‐systemic approaches including early‐onset cognitive training, physical activity, and psychosocial assistance. However, no pharmacological treatment is approved to counteract this decline. According to the most advanced conceptualization of Geroscience, tackling the molecular mechanisms underpinning the aging process should be a smart/feasible strategy to combat and/or delay the great majority of age‐related diseases, including cognitive decline. We think that a debate is needed urgently on if (and how) this strategy could be integrated in protocols to face DS‐associated dementia and overall unhealthy aging. In particular we propose that, on the basis of data obtained in different clinical settings, metformin is a promising candidate that could be exploited to counteract cognitive decline in DS.

In this review, we summarize current knowledge regarding the epigenetics of age-related diseases, focusing on those studies that have described DNA methylation landscape in cardio-vascular diseases, musculoskeletal function and frailty. We stress the importance of adopting the conceptual framework of “geroscience”, which starts from the observation that advanced age is the major risk factor for several of these pathologies and aims at identifying the mechanistic links between aging and age-related diseases. DNA methylation undergoes a profound remodeling during aging, which includes global hypomethylation of the genome, hypermethylation at specific loci and an increase in inter-individual variation and in stochastic changes of DNA methylation values. These epigenetic modifications can be an important contributor to the development of age-related diseases, but our understanding on the complex relationship between the epigenetic signatures of aging and age-related disease is still poor. The most relevant results in this field come from the use of the so called “epigenetics clocks” in cohorts of subjects affected by age-related diseases. We report these studies in final section of this review.