PRDM16 Reduces Cellular Senescence by Upregulating GSTM1.

Area of Science:

• Gerontology
• Molecular Biology
• Cell Biology

Background:

• Cellular senescence, characterized by accumulating senescent cells (SnCs), is a key aging process linked to organ dysfunction.
• The PRDM (PRDF1 and RIZ1 homology domain) protein family regulates diverse biological processes, but their role in senescence is largely unknown.

Purpose of the Study:

• To investigate the role of PRDM16, a PRDM family member, in cellular senescence and aging-related organ disorders.
• To elucidate the underlying molecular mechanisms by which PRDM16 influences senescence.

Main Methods:

• Comparative analysis of PRDM16 levels in aged versus young mice.
• Assessment of senescence and organ injury following global and tubular-specific Prdm16 deletion.
• Evaluation of PRDM16 gene delivery effects on senescence in vitro and in vivo.
• Mechanistic studies involving glutathione metabolism, oxidative DNA damage, and GSTM1 regulation.

Main Results:

• PRDM16 levels significantly decrease in multiple organs of aged mice.
• Prdm16 deletion exacerbates senescence and accelerates aging-related organ injury across various tissues.
• PRDM16 delivery attenuates senescence, improves glutathione metabolism, and inhibits oxidative DNA damage.
• PRDM16 directly upregulates glutathione S-transferase mu 1 (GSTM1) expression, and GSTM1 overexpression reverses Prdm16 deficiency-induced senescence.

Conclusions:

• PRDM16 plays a critical protective role against cellular senescence and age-related organ damage.
• PRDM16 functions by enhancing glutathione metabolism and mitigating oxidative DNA damage, partly through GSTM1.
• PRDM16 represents a promising therapeutic target for anti-aging interventions.