Aptamers as Diagnostic and Therapeutic Agents for Aging and Age-Related Diseases

Abstract

In the 21st century, the demographic shift toward an aging population has posed a significant challenge, particularly with respect to age-related diseases, which constitute a major threat to human health. Accordingly, the detection, prevention, and treatment of aging and age-related diseases have become critical issues, and the introduction of novel molecular recognition elements, called aptamers, has been considered. Aptamers, a class of oligonucleotides, can bind to target molecules with high specificity. In addition, aptamers exhibit superior stability, biocompatibility, and applicability, rendering them promising tools for the diagnosis and treatment of human diseases. In this paper, we present a comprehensive overview of aptamers, systematic evolution of ligands by exponential enrichment (SELEX), biomarkers associated with aging, as well as aptamer-based diagnostic and therapeutic platforms. Finally, the limitations associated with predicting and preventing age-related conditions are discussed, along with potential solutions based on advanced technologies and theoretical approaches.

Keywords: age-related disease; aging; aptamer; circadian rhythm; diagnosis; therapeutics.

Figure 1

Overview of this study. (A) Schematic illustration of aging hallmarks and various age-related diseases. (B) Aptamer-based diagnostic and therapeutic application for age-related problems.

Figure 2

Schematic illustration of Systematic Evolution of Ligands by Exponential Enrichment (SELEX). The SELEX process includes three main steps: binding, elution, and amplification. The cycle is repeated for 1 to 15 rounds, depending on the enrichment strategy. In the last round, aptamers are identified through sequencing and characterization.

Figure 3

Aptamer-based optical biosensing platforms. (A) Label-free colorimetric aptasensor based on an aptamer-polythymine (polyT)-polyadenine (polyA)- gold nanoparticle (pA-pT-apt@AuNPs) platform for Aβ40-O detection. Reprinted with permission from [118]. (B) Schematic illustration of a dually amplified colorimetric aptasensor for Aβo detection. Reprinted with permission from [119]. (C) Schematic illustration of SPR aptasensor for HER2-positive exosomes using tyramine signal amplification triggered by target-induced molecular aptamer beacon conversion. Adapted from [122]. (D) Schematic illustration of novel BLI-ELASA-based aptasensor for GDF15 detection. Adapted with permission from [124].

Figure 4

Aptamer-based electrochemical biosensors. (A) Schematic illustration of a sandwich-type, non-invasive electrochemical aptasensor for PD-L1+ exosome detection. DPV signals are generated by the peroxidase-like catalytic activity of PdCuB MNs. Adapted from [131]. (B) Schematic illustration of PAD-based aptasensor. Polypyrrole (Ppy) immobilizes anti-VEGF aptamers on the screen-printed carbon electrode (SPCE) surface for PAD evaluation via potential pulse sequences at +0.6 V and +0 V. Q_ads is the changes in charge due to adsorbed species. Adapted with permission from [132]. (C) Schematic illustration of EIS-based aptasensor functionalized with Aβ-40-specific aptamers, showing surface potential detection before (a) and after (b) Aβ-40 peptide interaction. Adapted with permission from [129]. (D) Schematic illustration of FET-based reusable aptasensor using anti-VEGF aptamer-conjugated carboxylated polypyrrole nanotubes (CPNTs), which detect the signal through a three-terminal transistor configuration. Reprinted with permission from [133].

Figure 5

Aptamer-based therapeutic strategies for neurodegenerative diseases. (A) Schematic illustration showing high-affinity aptamers binding to the N- and C-termini of α-synuclein, thereby inhibiting its aggregation in vitro. Upon cellular uptake, these aptamers reduce α-syn aggregation in vivo and facilitate their degradation via the lysosomal pathway, rescuing mitochondrial dysfunction and cellular defects induced by α-syn overexpression. Reprinted from [149]. (B) Schematic illustration of a circular bispecific aptamer traversing an in vitro BBB model. The aptamer incorporates transferrin receptor (TfR)- and tau-targeting sequences (IT2a) and is labeled with a fluorescein isothiocyanate fluorescence tag. The therapeutic mechanism includes inhibition of (1) tau hyperphosphorylation, (2) tau oligomerization, and (3) tau aggregation. Adapted with permission from [151]. Copyright (2020) American Chemical Society.

Figure 6

Aptamer-based therapeutic strategies for osteoporosis using anti-sclerostin DNA aptamer. (A) Schematic illustration of MSN fabrication and the synthesis steps of DNA-nanomedicine (DNAM) using surface-modified dendritic mesoporous silica nanoparticle (MSN) with anti-sclerostin DNA aptamers (Aptscl56) after amination (MSN-NH₂) and PEGylation (PEGM). (B) Schematic illustration of the mechanism of the bone-targeting and therapeutic efficacy of sclerostin aptamers. DNAM attaches to bone calcium and regulates serum sclerostin level, enabling osteoporosis treatment. (A,B) are adapted with permission from [165].

Figure 7

Aptamer-based therapeutic strategies for cancer. (A) Schematic illustration of an anti-cancer approach using the aptPD-L1 aptamer. This aptamer blocks PD-1/PD-L1 interactions and induces cytokine production (IL-2, TNF-α, IFN-γ, CXCL9, CXCL10), suppressing tumor angiogenesis and enhancing T cell function. Reprinted from [166]. (B) Schematic illustration of Aptamer-based photothermal cancer therapy using gold nanorods. The sgc8c aptamer targets HeLa cells, which are irradiated with 808 nm near-infrared light for 10 min. Cell death is confirmed via propidium iodide staining, demonstrating high selectivity and efficacy. Adapted with permission from [174]. Copyright (2008) American Chemical Society.