Simple molecules make difference: short peptides play a novel role in slowing senescence

Area of Science:

• Molecular Biology
• Gerontology
• Genomics

Background:

• Short peptides, encoded by small open reading frames, are emerging regulators of cellular senescence.
• Unlike non-coding RNAs, these peptides are evolutionarily conserved and crucial for maintaining cellular function.
• Their roles in biological processes, including aging and disease, are increasingly recognized but mechanistically complex.

Purpose of the Study:

• To review evidence demonstrating how short peptides slow senescence by interacting with core aging hallmarks across species.
• To explore the precise molecular targets modulated by short peptides, such as SERCA pumps and Bcl-2 complexes.
• To discuss the therapeutic potential of short peptides in extending healthspan and mitigating age-related pathologies.

Main Methods:

• Cross-species literature review focusing on nematodes to mammals.
• Analysis of studies investigating short peptide interactions with aging hallmarks.
• Examination of evidence for peptide disorder accelerating aging and therapeutic administration extending healthspan.

Main Results:

• Short peptides precisely modulate aging-related targets like SERCA pumps and Bcl-2 complexes.
• Disruption of short peptides accelerates age-related diseases, while their administration extends healthspan in animal models.
• Short peptides exhibit significant biological functions despite challenges in detection and delivery.

Conclusions:

• Short peptides represent a promising therapeutic strategy for healthy aging by targeting fundamental aging processes.
• Engineered peptide variants and gene therapies offer potential for clinical translation in aging interventions.
• Short peptides bridge molecular mechanisms with systemic resilience, redefining aging research.