<i>Lactobacillus amylovorus</i> KU4 inhibits adipocyte senescence in aged mice through necdin regulation of p53 activity.
- 2025-09-03
- Aging 17(9)
- Garam Yang
- Eunjeong Hong
- Hyuno Kang
- Sejong Oh
- Eungseok Kim
- PubMed: 40906540
- DOI: 10.18632/aging.206314
Previously, we reported that Lactobacillus amylovorus KU4 (LKU4) ameliorates diet-induced metabolic disorders by regulating adipose tissue (AT) physiology. Since metabolic disorders and age-related pathological conditions mutually exacerbate each other, this study hypothesizes that LKU4 may protect against adipose senescence during aging. Thus, this study demonstrates that LKU4 administration suppresses age-related metabolic dysfunction and aging phenotypes in AT of 24-month-old mice. Furthermore, LKU4 suppressed the expression of senescence marker genes, including p53, in the AT of these mice in parallel with the upregulation of necdin (NDN). Particularly, the effect of LKU4 on the expression of these genes was enhanced in adipocytes compared to stromal vascular fraction (SVF) cells. Mechanistically, NDN mediates the LKU4-induced suppression of p53 transcriptional activity by blocking the p53-p300 interaction, thereby inhibiting p53 acetylation. Both LKU4 and NDN consistently reduced the senescence-associated secretory phenotype (SASP) in the AT of aged mice and senescent 3T3-L1 adipocytes. Furthermore, ex vivo NDN silencing in the AT of D-galactose-induced aging mice abolished LKU4 protection against p53-induced adipose senescence, reducing adipogenesis and mitochondrial dysfunction in primary adipocytes. These findings demonstrate that LKU4 inhibits age-induced adipocyte senescence by modulating the p53-p300 interaction through NDN, thereby protecting against age-associated metabolic disorders.
Research Insights
| Supplement | Health Outcome | Effect Type | Effect Size |
|---|---|---|---|
| Lactobacillus amylovorus | Improved Metabolic Function | Beneficial | Moderate |
| Lactobacillus amylovorus | Increased Adipogenesis | Beneficial | Moderate |
| Lactobacillus amylovorus | Reduced Adipocyte Senescence | Beneficial | Moderate |
| Lactobacillus amylovorus | Reduced Mitochondrial Dysfunction | Beneficial | Moderate |
| Lactobacillus amylovorus | Reduced Senescence-Associated Secretory Phenotype | Beneficial | Moderate |