Aging poses one of the most urgent biomedical challenges of the 21st century, increasing vulnerability to chronic diseases and limiting healthspan in aging populations. Recent advances in aging research are transforming our understanding of aging from an inevitable decline to a multidimensional and potentially modifiable biological process. This special issue presents five invited reviews that collectively illustrate the recent progress in aging research. These articles introduce emerging concepts that shed light on the fundamental causes of aging, including the genetic architecture underlying human aging, senescence-driven fibrotic scarring arising from imperfect tissue repair, and the progressive erosion of epigenetic information in the brain. They further highlight promising avenues for intervention—such as epigenetic rejuvenation, the bidirectional interplay between the aging gut microbiome and host physiology, and the emergence of precision geronutrition. By integrating genetic, molecular, cellular, microbial, and nutritional perspectives, this collection emphasizes a future where extending human healthspan is both realistic and scientifically attainable.
Genetic Architecture of Human Longevity: Gim and colleagues analyze 45 GWAS studies, demonstrating that human aging and longevity are highly polygenic. They find that numerous small-effect alleles converge on conserved pathways, including lipid metabolism, inflammation, neuronal function, and DNA repair. The authors suggest future GWAS directions, such as refining aging phenotypes, incorporating diverse global cohorts, discovering rare variants, and employing integrative multi-omic approaches to enhance precision aging research.
Imperfect Repair and Senescent Niches: Kim and colleagues suggest a failure of tissue repair as an origin of tissue aging. With aging, transient wound-healing programs become chronic and give rise to pathological fibrotic niches consisting of heterogeneous senescent and scar-associated cells. These niches serve as an origin of tissue aging. They identify key signaling pathways and therapeutic strategies aimed at preventing or reversing early imperfect repair, proposing that targeting the tissue niche may provide new methods to delay aging and disease.
Epigenetic Aging of the Brain: Yang and colleagues emphasize the brain’s vulnerability to epigenetic erosion driven by DNA damage, chromatin remodeling, and inflammatory signals. They discuss significant manifestations such as DNA methylation drift, histone-mark dysregulation, and large-scale 3D genome remodeling, all contributing to cognitive decline and neurodegeneration with ages. The authors also highlight emerging rejuvenation strategies—such as partial Yamanaka-factor reprogramming and chemical epigenetic modifiers—that can restore youthful epigenetic landscapes and brain function while maintaining cellular identity.
Gut Microbiome and Aging: Min and colleagues summarize how aging alters the gut microbiota, leading to reduced diversity, depletion of beneficial commensals, and an increase in pro-inflammatory taxa. They present evidence that dysbiosis can actively contribute to metabolic dysfunction, immunosenescence, and neurodegeneration in older populations. The authors evaluate various strategies—including probiotics, prebiotics, postbiotics, dietary interventions, and fecal microbiota transplantation—as promising methods to restore microbial balance and promote healthy aging.
Precision Geronutrition and Biological Aging Clock: Ahn and colleagues introduce precision geronutrition, which merges geroscience with personalized nutrition. The individualized nutritional strategies influence core aging mechanisms such as nutrient-sensing pathways, inflammaging, mitochondrial dysfunction, and microbiome dysbiosis. They emphasize the importance of multi-omics data and biological aging clocks in personalizing dietary interventions and assessing their effectiveness. These approaches will promote a shift from disease treatment to a preventive and healthspan-focused approach to aging.
Collectively, these reviews highlight that aging is shaped by interconnected biological systems—genetic networks, tissue repair programs, epigenetic landscapes, microbial ecosystems, and nutrition-responsive pathways. This convergence illustrates aging as a dynamic and modifiable process, presenting opportunities for personalized, mechanism-based interventions to extend human healthspan.