DNA oligonucleotide treatment corrects the age-associated decline in DNA repair capacity

Area of Science:

• Molecular Biology
• Gerontology
• Dermatology

Background:

• Aging is associated with reduced DNA repair capacity (DRC).
• Key DNA repair proteins like p53 show decreased levels in older adults.
• This decline impacts the skin's ability to repair UV-induced DNA damage.

Purpose of the Study:

• To investigate if DNA oligonucleotides can restore DRC in aged cells.
• To determine the efficacy of thymidine dinucleotide (pTT) and a 5' phosphorylated 9 base oligonucleotide (p9mer) in enhancing DNA repair.
• To assess the potential of oligonucleotide treatment in mitigating UV radiation risks in the elderly.

Main Methods:

• Fibroblasts from donors of varying ages were pretreated with pTT, p9mer, or diluent.
• Cells were subsequently exposed to solar-simulated UV irradiation.
• Western blot analysis quantified protein levels, and thymine dimer removal rates were measured.

Main Results:

• Age-related decreases (40%-80%) in DNA repair proteins (p53, p21, XPA, RPA, ERCC1, PCNA) were observed.
• Oligonucleotide treatment significantly upregulated these proteins (200%-650%).
• Oligonucleotide-treated cells showed significantly higher thymine dimer removal rates, comparable to younger cells.

Conclusions:

• DNA oligonucleotides (pTT and p9mer) effectively correct age-associated declines in DNA repair capacity.
• Topical oligonucleotide treatment may enhance DNA repair in older adults.
• This approach could reduce carcinogenic risk from solar UV irradiation in the elderly.