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Niacin restriction affected SIRT, PARP responses to skin photodamage

Sirtuins and poly ADP-ribose polymerases are significant factors in resistance to photodamage and point to specific sirtuins that respond to photodamage, according to recent data.

Researchers obtained samples of three actinic keratosis and five squamous cell carcinomas, along with respective normal adjacent skin biopsies, from a project (No. 08-0201-04) reviewed by the University of Arizona. Their goal was to report expression of the seven sirtuin (SIRT) family members in human skin.

Researchers found that photodamage induced dynamic changes in SIRT expression with up-regulation of both SIRT1 and SIRT4 mRNAs. Specific losses of SIRT proteins occurred soon after photodamage, followed by accumulation, particularly for SIRT4.

Niacin restriction caused:

• up-regulation of SIRTs 2 and 4
• altered SIRT responses to photodamage
• abrogation of poly ADP-ribose polymerases (PARP) activation following photodamage
• increased acetylated proteins
• increased inherent DNA damage
• greater sensitivity to photodamage that is entirely reversed by repleting niacin

“These data point to niacin conversion to NAD ⁺ as a critical factor in resistance to photodamage and suggest that elucidating the roles PARPs and SIRTs play both during altered NAD⁺ availability and in response to photodamage are essential for understanding mechanisms that maintain skin homeostasis and prevent skin cancer,” the researchers wrote.