Anti-Senescence Targets Based on Metabolic Pathways

Anti-senescence strategies often target metabolic pathways to delay or reverse cellular aging processes. Key pathways such as the pentose phosphate pathway (PPP) and mitochondrial metabolism are modulated to reduce oxidative stress and increase cellular resilience. By optimizing these pathways, anti-senescence approaches aim to maintain energy production, prevent accumulation of damage, and preserve stem cell function. Ultimately, these interventions may improve tissue homeostasis and mitigate age-related decline.

Point of Interest
- A switch that results in the accumulation of glycerol-3-phosphate (G3P) and phosphoethanolamine (pEtN) links lipid metabolism to the senescence gene expression program in human fibroblasts.

- p53-dependent glycerol kinase activation and post-translational modifications drive this metabolic switch, promoting triglyceride accumulation and senescence.

- Scavenging G3P and pEtN reduces their accumulation, acting senomorphically and potentially providing a therapeutic approach to target senescence.

Point of Interest
- The pluripotency transcription factor NANOG rejuvenates senescent mitochondria by restoring the key proline biosynthetic enzymes PYCR1 and PYCR2, thereby improving cellular metabolism.

- Proline supplementation induces mitophagy, alleviates mitochondrial respiratory impairment and improves mitochondrial clearance in senescent cells.

- Proline treatment mitigates the hallmarks of aging, including DNA damage, inflammation, and impaired differentiation, by restoring mitochondrial function.

Point of Interest
- ACLY, critical for acetyl-CoA synthesis, drives the pro-inflammatory SASP in senescent cells independent of growth arrest.

- ACLY-dependent acetyl-CoA activates SASP gene enhancers, increasing BRD4 recruitment and promoting SASP activation.

- Chemical inhibition of the ACLY-BRD4 axis suppresses SASP in aged mice, providing a potential target for promoting healthy aging.

Metabolic shift to glycolysis in senescenct cells

NAD(+) levels decline during the aging process, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies*. Here, we try to redemonstrate this phenomenon in the doxorubicin (DOX)-induced cellular senescence model with a comprehensive analysis of our products.

*S. Imai, et al., Trends Cell Biol, 2014, 24, 464-471

Products in Use
① DNA Damage Detection Kit - γH2AX
② Cellular Senescence Detection Kit - SPiDER-βGal
③ NAD/NADH Assay Kit-WST
④ JC-1 MitoMP Detection Kit
⑤ Glycolysis/OXPHOS Assay Kit、Lactate Assay Kit-WST