Inflammatory cytokines, particularly interleukin-6 (IL-6), are key initiators and drivers of both acute and chronic diseases, as well as the processes of human aging. Currently, various laboratory methods are employed to determine cytokines, primarily based on antibodies. Although these methods are continuously improved, specific, and reliable, there exists a significant need for the development of analytical methods capable of rapid, reliable, specific, and highly sensitive determination of the concentration of various proteins, including IL-6. These methods should be suitable for point-of-care testing or for wearable devices that enable continuous monitoring of biomarkers. The creation of such devices is expected to lead to significant progress in monitoring the treatment of diseases associated with the development of acute and chronic inflammation. In our review, we have gathered and analyzed studies that will aid in assessing the possibilities and prospects for the development of aptasensors for the determination of IL-6. This includes data on the diagnostic significance of IL-6, the range of concentrations in both normal and pathological conditions, existing variants of aptamers specific to it, and the technologies employed in the creation of aptasensors. In conclusion, we identify the challenges associated with the development and implementation of aptasensors and draw conclusions regarding the prospects for advancement in this field. Ultimately, we believe that the creation of reliable and non-invasive sensors for IL-6 based on aptamers will provide a competitive alternative not only to traditional antibodies but also to new types of biorecognition elements, such as nanobodies or receptors

Объединенный иммунологический Форум – 2008.30 июня – 5 июля 2008 года, Санкт-Петербург, Россия.

An aptamer’s low mass confines the label-free response to hundredths of a nanometer, where artifacts mimic binding yet yield computable dissociation constants. To define and test a priori criteria distinguishing binding from artifact, 88 computationally designed aptamers against seven human proteins were studied by biolayer interferometry in two orthogonal configurations, with control antibodies. Six criteria, fixed in advance, are reported as a priori decision rules, not validated requirements. Control antibodies validated 6 of 8 preparations; for the other 68 pairs, the maximum response was 0.019–0.219 nm, bounding K_D at ≥8.6 µM, 120-fold above the 70 nM threshold. Two of three signals clearing it gave exponents far above the 1:1 expectation (1.04 vs. 0.31; 0.85 vs. 0.41); the third failed parameter consistency (K_D scatter ×28). Rankings on two PCSK9 preparations did not correlate (ρ = −0.26); predicted and experimental K_D differed by 3–7 orders of magnitude (ρ = 0.497, n = 25). No aptamer reached the predefined affinity under the conditions tested. Local fitting returns internally consistent K_D for data incompatible with a 1:1 model; we propose isotherm verification and antibody validation of every preparation as minimal requirements. No positive-control aptamer was available, limiting interpretation.

Increased life expectancy without proportional increase in healthy lifespan poses a significant challenge for contemporary healthcare. There is a need to shift the focus of healthcare from treating age-related diseases to addressing the underlying factor of their development (aging). Organ-specific strategies for replacement therapy are being considered together with development of systemic anti-aging therapies. In this review, we analyze current advancements of ex situ machine perfusion not only for organ preservation prior to transplantation, but also as a platform for assessment, restoration, and modification of organs. Integration of machine perfusion with advanced biotechnologies (gene therapy, mesenchymal stem cell therapy, senotherapy, and aptamer-based biosensors for real-time monitoring of cytokines) opens new opportunities for creation of organs resistant to aging and ischemia-reperfusion injury. We discuss the impact of organ age on organismal aging rate and evaluate potential of combined approaches involving machine perfusion alongside molecular and cellular technologies as a platform for anti-aging replacement therapy.