BRI1-EMS-SUPPRESSOR 1 (BES1)/BRASSINAZOLE-RESISTANT 1 (BZR1) transcription factors serve as core regulators of brassinosteroid (BR) signal in seed plants, where they control diverse developmental processes, including cell elongation, vascular development, and environmental responses; however, their evolutionary trajectory and functional diversification in early-diverging land plants remain poorly characterized. In this study, we systematically characterized the BES1/BZR1 gene family across 12 representative bryophyte species covering hornworts, liverworts and mosses, with Arabidopsis thaliana included as a vascular plant outgroup. In total, 19 non-redundant BES1/BZR1 homologs were identified within bryophyte genomes. Phylogenetic reconstruction, synteny analysis and Ka/Ks selection pressure analyses collectively revealed that this gene family is evolutionarily conserved throughout bryophytes, with moss-specific lineage expansion; most paralogous gene pairs have experienced strong purifying selection during evolution. Further analyses of gene structural organization, conserved protein motifs and cis-acting promoter elements uncovered universally conserved core domains alongside lineage-specific structural and regulatory variations. Subcellular localization assays demonstrated that the majority of tested bryophyte BES1/BZR1 proteins primarily accumulate in the nucleus, and autoluminescent reporter assays verified that multiple homologs modulate E-box-driven transcriptional activity. Transcriptional expression profiling indicated that BES1/BZR1 genes from Marchantia polymorpha and Sphagnum fallax are transcriptionally responsive to exogenous BR treatment, while several paralogs in S. fallax additionally exhibit altered expression under drought stress. Collectively, our results demonstrate that the BES1/BZR1 family originated at an early stage of land plant evolution, followed by lineage-specific gene expansion and divergent transcriptional regulation in bryophytes. This work advances our understanding of ancestral BR signaling and stress response modules in the early terrestrial plant lineages.

Aging-related decline involves changes in oxidative stress, inflammation, mitochondrial function, telomere maintenance, metabolic regulation, and extracellular matrix homeostasis. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement and searched PubMed, Scopus, Embase, and Web of Science for English-language studies published from 1993 to 2025. Twelve primary studies met the eligibility criteria: four randomized clinical studies, four animal studies, one in vitro mechanistic study, and three delivery-system/formulation studies. Risk of bias was assessed using Cochrane Risk of Bias 2 (RoB 2), the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool, and a review-specific domain-based checklist informed by the National Toxicology Program/Office of Health Assessment and Translation framework. Representative compounds, including resveratrol, astragaloside IV, Ganoderma lucidum polysaccharide, epigallocatechin-3-gallate (EGCG) and betulinic acid, were associated with mitochondrial regulation, antioxidant defense, cytoskeletal stability, gut–brain signaling, extracellular-matrix protection, and longevity-related signaling. Nanoliposomes and poly(lactic-co-glycolic acid) (PLGA) nanoparticles improved selected stability, penetration, and pharmacokinetic outcomes. However, the evidence base was heterogeneous and predominantly preclinical; human evidence was limited to four relatively small studies, and certainty ranged from moderate to very low. The findings support mechanistic and translational potential but do not establish definitive anti-aging efficacy in humans.