Transposable elements (TEs), or mobile genetic elements, are fragments of DNA capable of moving from one genomic location to another. Traditionally, transposons have been considered selfish genetic elements because they increase their copy number by jumping into new genomic locations and causing genomic instability. In mammals, TEs make up a substantial portion of the genome, far exceeding the fraction occupied by protein-coding genes or regulatory elements such as promoters or enhancers, but only a small fraction is still able to mobilize. Additionally, in most adult cells, TE expression is largely silenced by epigenetic mechanisms and other pathways that protect the genome from the deleterious consequences of TE expression. However, during gametogenesis and early development, epigenetic reprogramming creates a window in which TEs can be expressed. Throughout evolution, host genomes have repurposed transposon-derived sequences to exert a function in a process known as co-option. Here, we summarize how TE expression is regulated and can be harnessed for the host's benefit, with a particular focus on the co-option of TEs during gametogenesis and early development, and present current evidence for their extensive regulatory roles.
Interferons are key mediators of antiviral defense. They enable infected cells and specialized immune populations to mount rapid transcriptional responses that restrict viral replication and support immune activation. Type I and type III interferons share many antiviral properties, but their effects are determined by distinct receptor distributions, signaling dynamics, and tissue localization. While both families contribute to protection against infection, this chapter focuses primarily on the regulation and function of type I interferons. The induction of interferons depends on the activation of pattern recognition receptors that detect viral nucleic acids and trigger signaling cascades involving IRF and NF-κB transcription factors. These pathways control tightly regulated transcriptional and epigenetic programs that drive interferon gene expression and the induction of interferon-stimulated genes. Balanced regulation is essential, as excessive or persistent signaling can cause immunopathology and chronic inflammation. Genetic variation in interferon pathways influences susceptibility to viral infections, and defects in interferon regulation contribute to several monogenic interferonopathies. Plasmacytoid dendritic cells are a major source of type I interferons and illustrate the complexity of cellular specialization in antiviral defense. Understanding these mechanisms is essential for the development of therapies that enhance antiviral protection or limit pathogenic inflammation in chronic infections and autoimmune disease.
This chapter reviews the current understanding of the role of transposable elements (TEs) in the aging process. TEs represent a significant proportion of mammalian genomes and, far from being "junk DNA", they harbor important functions as regulators of gene expression and important drivers of evolution. Their classification, epigenetic mechanisms that control their silencing, and the evidence for their progressive activation during physiological aging across multiple species are discussed.Aging is associated with a global loss of heterochromatin, which triggers TE derepression, and unleashes two major pathological consequences. First, the increased activity of these elements generates genomic instability through insertional mutagenesis, DNA damage, and changes in genome organization. Second, TE-derived nucleic acids are recognized by DNA sensors such as cGAS-STING and RNA sensors including RIG-I and MDA5, perpetuating interferon responses that contribute to the age-associated functional decline. Diverse therapeutic strategies to control TE dysregulation are presented, including reverse transcriptase inhibitors (NRTIs), lifestyle interventions, genetic approaches, and SIRT6 activation. These interventions have demonstrated efficacy in extending lifespan, suppressing TE expression, reversing inflammatory phenotypes, ameliorating age-related decline, and restoring TE epigenetic silencing in experimental models. Finally, the significance of TE-based biomarkers is highlighted, emphasizing their vital role as both effectors and indicators of biological age and their utility in assessing disease risk. Together, these findings position TE dysregulation as a fundamental aging mechanism and a promising therapeutic target for promoting healthy aging.
Transposable Elements (TEs) have the ability to transpose, and have populated all known eukaryotic genomes to date. Nowadays, their role in many aspects of biology, from population diversity to gene regulatory networks is well recognized. OMICS technologies, thanks to their genome-wide scale, provide an unparalleled resource to understand TE biology. However, due to their repetitive nature, TE analysis is not routinely carried out. In this chapter, I will provide the basic theoretical framework that will allow researchers to gain a first understanding of TEs without the need of significant alteration to established analysis pipelines. Then, I will present an overview on how TE analyses have been carried out for different OMICS data, as well as advantages and disadvantages on these approaches. Collectively, this chapter will provide the necessary background to explore TE contribution, so prospective researchers continue to reveal the multifaceted role of TEs in healthy and disease biology.
Transposable elements (TEs), once dismissed as genomic "junk," are now recognized as major forces shaping the architecture, function, and evolution of the nervous system. Among them, retrotransposons-particularly Long Interspersed Nuclear Elements (LINEs) play a dual role as both architects of neuronal diversity and saboteurs of genomic integrity. During neurodevelopment, transient retrotransposon activation contributes to somatic mosaicism, activity-dependent transcription, and synaptic plasticity, thereby enhancing cognitive adaptability. However, the same mechanisms that promote neuronal complexity render the brain vulnerable to aging and disease. Epigenetic erosion during senescence leads to derepression of LINEs and endogenous retroviruses, triggering genomic instability and neuroinflammation through the cGAS-STING pathway. Such "retrotransposon storms" are increasingly linked to neurodegenerative disorders, notably Alzheimer's disease, where tau- and Aβ-driven chromatin relaxation facilitates TE reactivation. The chapter integrates evidence from molecular, cellular, and translational research, highlighting therapeutic opportunities, from reverse transcriptase inhibitors like lamivudine to epigenetic and innate immune modulators, that aim to restore genomic homeostasis. Understanding retrotransposons as both evolutionary catalysts and pathological triggers reframes their role in brain biology and positions them as novel therapeutic targets in aging and neurodegeneration.
