Mitochondrial (Dys) Function in Inflammaging: Do MitomiRs Influence the Energetic, Oxidative, and Inflammatory Status...

Area of Science:

• Gerontology
• Molecular Biology
• Cell Biology

Background:

• Aging is characterized by chronic low-grade inflammation (inflammaging), linked to age-related diseases.
• Senescent cells exhibit a senescence-associated secretory phenotype (SASP) that fuels inflammaging.
• Cellular senescence involves altered microRNA expression and mitochondrial activity, key regulators of SASP.

Purpose of the Study:

• To synthesize novel findings on mitochondria's role in SASP and inflammaging.
• To propose a network linking nuclear-encoded senescence-associated miRNAs (SA-miRNAs) to mitochondrial regulation in aging cells.
• To explore SA-miRNAs' potential translocation to mitochondria (SA-mitomiRs) and their impact.

Main Methods:

• Literature synthesis of recent findings on mitochondria, SASP, and inflammaging.
• Conceptual network proposal linking SA-miRNAs, mitochondria, and aging.
• Discussion of specific SA-miRNAs (e.g., miR-146a) as proof-of-principle models.

Main Results:

• SA-miRNAs can translocate to mitochondria (SA-mitomiRs).
• SA-mitomiRs may influence the energetic, oxidative, and inflammatory status of senescent cells.
• Several SA-miRNAs (let-7b, miR-1, miR-130a-3p, miR-133a, miR-146a-5p, miR-181c-5p, miR-378-5p) are discussed.

Conclusions:

• A network exists where SA-miRNAs impact mitochondrial function in aging.
• This provides a metabolic and epigenetic view of senescence, targeting inflammaging.
• Potential therapeutic strategies to decelerate aging and prevent age-related diseases can be developed.