Statistical strategies and stochastic predictive models for the MARK-AGE data.

MARK-AGE aims at the identification of biomarkers of human aging capable of discriminating between the chronological age and the effective functional status of the organism. To achieve this, given the structure of the collected data, a proper statistical analysis has to be performed, as the structure of the data are non trivial and the number of features under study is near to the number of subjects used, requiring special care to avoid overfitting. Here we described some of the possible strategies suitable for this analysis. We also include a description of the main techniques used, to explain and justify the selected strategies. Among other possibilities, we suggest to model and analyze the data with a three step strategy.

Systemic impact molds mesenchymal stromal/stem cell aging.

Aging is associated with an accruing emergence of non-functional tissues. Mesenchymal stem cells (MSC) bring forth progenitors with multi-lineage differentiation potential, yet, they also exhibit anti-inflammatory and tissue-protective properties. Due to aging, altered tissue microenvironments constrict controlled stem cell proliferation and progenitor differentiation, thus diminishing the fitness of MSC. Therefore, deepening our understanding of metabolic, molecular and environmental factors impacting on MSC during human aging as well as providing new vistas on their role in promoting healthy aging and preventing age-associated disease is pivot. It is anticipated that integrative quantification of systemic parameters dominantly impacting on MSC will also enable effective personalized prognosis and provision of effective early medical interventions. Working along this line, it can be envisaged that standards in medical therapies can be individually adjusted by accounting not solely for the patient's chronological age or other physical parameters rather than specific physiological parameters which are believed to functionally shape stem cell niches within the bone marrow.

Pre-Operative, High-IL-6 Blood Level is a Risk Factor of Post-Operative Delirium Onset in Old Patients.

BACKGROUND: Post-operative delirium (POD) is a common complication in elderly patients undergoing surgery, but the underpinning causes are not clear. We hypothesized that inflammaging, the subclinical low and chronic grade inflammation characteristic of old people, can contribute to POD onset. Accordingly, we investigated the association of pre-operative and circulating cytokines in elderly patients (>65 years), admitted for elective and emergency surgery. METHODS: This is a secondary analysis of a sub-cohort of patients belonging to a previous large case-control study, where 351 patients were clinically and cognitively thoroughly characterized, together with the assessment of POD (47 patients) by confusion assessment method and delirium rating scale. Seventy-four pre-operative plasma samples were selected from a larger bio-bank and they included 37 subjects with POD and 37 without POD. Inflammaging related cytokines, i.e., IL-1ß, IL-2, IL-6, IL-8, IL-10, and TNF-α, were assayed by ELISA in pre-operative blood samples; univariate and multivariable analyses have been applied to identify cytokines independently associated to POD. Associations of cytokine levels with functional status, cognitive decline, intra-hospital mortality, and comorbidity were also analyzed independently of POD onset. RESULTS: High IL-6 and low-IL-2 levels were significantly associated with POD. After adjustment for potential confounders in multivariate analysis, high level of pre-operative IL-6 was confirmed to be significantly associated with risk of POD onset. High level of IL-6 was also associated with several baseline features (including poor functional status, cognitive impairment, emergency admission, and higher comorbidity burden) and intra-hospital mortality. CONCLUSION: Pre-operative, high-plasma level of IL-6 (≥9 pg/mL) was significantly associated with POD onset. We propose IL-6 as an additional risk factor of POD onset together with the previously identified factors. Discovery of all risk factors contributing to POD onset will permit to improve hospitalized patient management and the decrease of healthcare cost.

Circulating levels of adipokines and IGF-1 are associated with skeletal muscle strength of young and old healthy subjects.

It is known that adipose tissue mass increases with age, and that a number of hormones, collectively called adipokines, are produced by adipose tissue. For most of them it is not known whether their plasmatic levels change with age. Moreover, it is known that adipose tissue infiltration in skeletal muscle is related to sarcopenia and loss of muscle strength. In this study we investigated the age-related changes of representative adipokines and insulin-like growth factor (IGF)-1 and their effect on muscle strength. We studied the association between circulating levels of adiponectin, leptin, resistin and IGF-1 and muscle strength. This cross-sectional study included 412 subjects of different age (152 subjects aged 18-30 years and 260 subjects aged 69-81 years) recruited within the framework of the European research network project "Myoage". The levels of adiponectin (both in male and female subjects) and leptin (only in males) were significantly higher in old subjects compared to young, while those of IGF-1 were lower in old subjects. In old subjects adiponectin, resistin and the resistin/IGF-1 ratio (but not IGF-1 alone) were inversely associated with quadriceps torque, while only adiponectin was inversely associated with handgrip strength independently from percentage of fat mass, height, age, gender and geographical origin. The ratio of leptin to adiponectin was directly associated with handgrip strength in both young and old subjects. These results suggest that in humans the age-associated loss of strength is associated with the levels of representative adipokines and IGF-1.

Immune system, cell senescence, aging and longevity--inflamm-aging reappraised.

Inflamm-aging, that is the age-associated inflammatory status, is considered one of the most striking consequences of immunosenescence, as it is believed to be linked to the majority of age-associated diseases sharing an inflammatory basis. Nevertheless, evidence is emerging that inflamm-aging is at least in part independent from immunological stimuli. Moreover, centenarians who avoided or delayed major inflammatory diseases display markers of inflammation. In this paper we proposed a reappraisal of the concept of inflamm-aging, suggesting that its pathological effects can be independent from the total amount of pro-inflammatory mediators, but they would be rather associated with the anatomical district and type of cells where they are produced and where they primarily act.