Senescence-Mitophagy Associated LncRNA (lncR-SMAL)

Senescence-Mitophagy Associated LncRNA (lncR-SMAL, also called lncRNA LOC105378097) is a heart-enriched long non-coding RNA whose expression rises with age, especially in serum and cardiomyocytes of humans and mice[1][2]. It directly binds Parkin protein, promoting its ubiquitin-proteasome degradation, leading to impaired mitophagy and accelerated cellular senescence in heart tissue, characterized by increased p53, p21, and senescence-associated secretory phenotype (SASP) marker genes such as TNF-α, IL-6, and matrix metalloproteinases[1]. Knockdown of lncR-SMAL by siRNA rescues mitophagy defects, extends telomere length, restores telomerase activity, and ameliorates age-associated cardiac dysfunction[1]. No clinically approved drugs directly target lncR-SMAL yet, but its expression and effects make it a candidate therapeutic target and circulating biomarker for age-related cardiac decline[1][2].

Other names

LNCR-SMALlncRNA LOC105378097Senescence-Mitophagy Associated LncRNA

siRNA-mediated knockdown: Reduces lncR-SMAL to ameliorate cardiac senescence by restoring Parkin levels and mitophagy. Indirect modulation: Drugs increasing mitophagy or Parkin (such as BAFA1 or specific mitophagy activators in research context) may counteract effects of lncR-SMAL.