NAD+ as the link between oxidative stress, inflammation, caloric restriction, exercise, DNA repair, longevity, and health span

Poljšak, Borut (author), Milisav, Irina (author)

Oxidative stress and decreased DNA damage repair in vertebrates increase with age also due to lowered cellular NAD+. NAD+ depletion may play a major role in the aging process at the cellular level by limiting (1) energy production, (2) DNA repair, and (3) genomic signaling. In this study, we hypothesize that it is not NAD+ as a cofactor in redox reactions and coenzyme in metabolic processes that has the ultimate role in aging, but rather the role of NAD+ in cellular signaling when used as substrate for sirtuins (SIRT1-7 in mammals) and PARPs [Poly(ADP-ribose) polymerases]. Both sirtuins and PARPs influence many transcription factors and can affect gene expression. As a signaling molecule, NAD+ is consumed in the reaction donating ADP-ribose and releasing nicotinamide (NAM) as a by-product. It seems that aging at the cellular level is associated with a decline of NAD+ and that NAD+ restoration can reverse phenotypes of aging by inducing cellular repair and stress resistance. Adequate intracellular NAD+ concentrations may be an important longevity assurance factor, while lowered cellular NAD+ concentration may negatively influence the life span.

• Language: English
• Keywords: ageing, NAD+, oxidative stress, niacin, sirtuins, Poly(ADP-ribose)Polymerases, degenerative disease
• Typology: 1.01 - Original Scientific Article
• Organization: ZF - Faculty of Health Sciences
• Publication status: Published
• Publication version: Author Accepted Manuscript
• Year: 2016
• Number of pages: Str. 406-413
• Numbering: Vol. 19, no. 5
• PID: 20.500.12556/RUL-106526
• UDC: 612.67/.68
• ISSN on article: 1557-8577
• DOI: 10.1089/rej.2015.1767
• COBISS.SI-ID: 5019243
• Publication date in RUL: 01.03.2019

Record is a part of a journal

• Title: Rejuvenation research
• Shortened title: Rejuvenation res.
• Publisher: Mary Ann Liebert Inc.
• ISSN: 1557-8577
• COBISS.SI-ID: 521921049

Projects

• Funder: EC - European Commission
• Funding programme: H2020
• Project number: 664536
• Name: Advanced Regional Translation of Excellence into Medical Innovations for Delayed Aging
• Acronym: ARTEMIDA