Aptamer Sensors for Inflammaging Biomarkers: Principles of Molecular Recognition, Analytical Platforms, and...

Inflammaging, a chronic, low-grade systemic inflammatory state that develops with advancing age, is one of the key drivers of age-associated pathology and promotes the emergence of the senescence-associated secretory phenotype (SASP). Timely quantitative monitoring of pro-inflammatory and SASP-associated biomarkers therefore demands highly sensitive analytical platforms capable of reliable performance in complex biological matrices. Aptamer-based biosensors (aptasensors), which employ short single-stranded oligonucleotides offering high affinity and specificity for molecular recognition, have emerged as promising alternatives and complements to conventional antibody-based assays. This review provides a comprehensive overview of aptasensor platforms developed for biomarkers of age-associated inflammation and identifies molecular targets of relevance to aging biology that remain unexplored. Following PRISMA guidelines, a systematic literature search of the PubMed database was conducted for studies published between 2020 and 2026. A total of 221 original studies met the inclusion criteria and were qualitatively analyzed, encompassing 47 biomarkers and seven classes of analytical platforms. The analysis revealed a pronounced research bias: 73% of published studies focused on just five well-established biomarkers - VEGF, CRP, IL-6, IFN-γ, and TNF-α - leaving many biomarkers with recognized relevance to aging without any aptasensor-based detection strategy. The review also discusses the molecular mechanisms underlying aptamer-target recognition, recent advances in SELEX technologies, and chemical modifications, including 2'-F nucleotides, locked nucleic acids (LNAs), SOMAmers, and spiegelmers, that enhance aptamer stability and affinity. Finally, we discuss the principal obstacles limiting clinical translation of aptamer technologies and propose priorities for future research, including multiplex ratiometric aptasensors for SASP cytokine profiling, aptamer-based extracellular vesicle capture as a route to intracellular biomarkers, and novel strategies for generating aptamers against currently inaccessible molecular targets.