Study2021Open access

Creatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts

Mahajan AS, Arikatla VS, Thyagarajan A, Zhelay T, Sahu RP, Kemp MG, Spandau DF, Travers JB

Nutrients · 13 citations

Review labels

Mechanisms only

Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.

How it was studied

Design
In vitro/mechanistic study (classified by our AI screen)
Studied in
Cells or lab samples
Main outcome
Mechanisms only

Who paid for it

Funding
Independent funding
Government
U.S. Department of Veterans Affairs
Government
National Institutes of Health
University or hospital
School of Medicine, Indiana University
Government
National Institute on Aging
Government
National Institute of General Medical Sciences
Government
NIH HHS
Government
Dayton VA Medical Center
Grants
U.S. Department of Veterans Affairs (I01 CX002241); National Institute on Aging (R01AG048946); U.S. Department of Veterans Affairs (I01 BX000853); National Institute of General Medical Sciences (R01GM130583); National Institutes of Health (1101CX000809); U.S. Department of Veterans Affairs (I01 CX001904); U.S. Department of Veterans Affairs (I01 CX001956); National Institutes of Health (AG048946); National Institutes of Health (R01 HL062996); National Institutes of Health (HL062996); National Institutes of Health (R01AG048946)

Based on 7 listed funder(s).

Publication

Published
2021-11-16 · Nutrients · vol. 13 · issue 11 · p. 4102
Publisher
Multidisciplinary Digital Publishing Institute
Cited
19 citations · more than 88% of similar papers · 2.2× the field average
References
52 works
Access
Open access (journal) · CC-BY
Research areas
Skin Protection and Aging · Telomeres, Telomerase, and Senescence · Sirtuins and Resveratrol in Medicine
Keywords
Senescence, Dermal fibroblast, Cell biology, Fibroblast, Skin Aging, Oxidative stress, Carcinogenesis, Biology, Chemistry, Cancer research, Endocrinology, Biochemistry, In vitro, Medicine
MeSH
fibroblasts, dermis, humans, hydrogen peroxide, creatine, niacinamide, insulin-like growth factor i, rna, messenger, oxidants, skin aging, aged, cellular senescence, senescence-associated secretory phenotype

8 authors

From US

  • Avinash S. MahajanWright State University
  • Venkata Sreekanth ArikatlaWright State University
  • Anita ThyagarajanWright State University
  • Tetyana ZhelayWright State University
  • Ravi P. SahuWright State University
  • Michael G. KempWright State University; Dayton VA Medical Center

Abstract

Dermal fibroblasts provide structural support by producing collagen and other structural/support proteins beneath the epidermis. Fibroblasts also produce insulin-like growth factor-1 (IGF-1), which binds to the IGF-1 receptors (IGF-1Rs) on keratinocytes to activate signaling pathways that regulate cell proliferation and cellular responses to genotoxic stressors like ultraviolet B radiation. Our group has determined that the lack of IGF-1 expression due to fibroblast senescence in the dermis of geriatric individuals is correlated with an increased incidence of skin cancer. The present studies tested the hypothesis that pro-energetics creatine monohydrate (Cr) and nicotinamide (NAM) can protect normal dermal human fibroblasts (DHF) against experimentally induced senescence. To that end, we used an experimental model of senescence in which primary DHF are treated with hydrogen peroxide (H2O2) in vitro, with senescence measured by staining for beta-galactosidase activity, p21 protein expression, and senescence associated secretory phenotype cytokine mRNA levels. We also determined the effect of H2O2 on IGF-1 mRNA and protein expression. Our studies indicate that pretreatment with Cr or NAM protects DHF from the H2O2-induced cell senescence. Treatment with pro-energetics post-H2O2 had no effect. Moreover, these agents also inhibited reactive oxygen species generation from H2O2 treatment. These studies suggest a potential strategy for protecting fibroblasts in geriatric skin from undergoing stress-induced senescence, which may maintain IGF-1 levels and therefore limit carcinogenesis in epidermal keratinocytes.

Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).

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