Cytoplasmic and Mitochondrial NADPH-Coupled Redox Systems in the Regulation of Aging
Open accessAbstract
The reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) protects against redox stress by providing reducing equivalents to antioxidants such as glutathione and thioredoxin. NADPH levels decline with aging in several tissues, but whether this is a major driving force for the aging process has not been well established. Global or neural overexpression of several cytoplasmic enzymes that synthesize NADPH have been shown to extend lifespan in model organisms such as Drosophila suggesting a positive relationship between cytoplasmic NADPH levels and longevity. Mitochondrial NADPH plays an important role in the protection against redox stress and cell death and mitochondrial NADPH-utilizing thioredoxin reductase 2 levels correlate with species longevity in cells from rodents and primates. Mitochondrial NADPH shuttles allow for some NADPH flux between the cytoplasm and mitochondria. Since a decline of nicotinamide adenine dinucleotide (NAD+) is linked with aging and because NADP+ is exclusively synthesized from NAD+ by cytoplasmic and mitochondrial NAD+ kinases, a decline in the cytoplasmic or mitochondrial NADPH pool may also contribute to the aging process. Therefore pro-longevity therapies should aim to maintain the levels of both NAD+ and NADPH in aging tissues.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Erg11 catalyzes 14-methylation of lanosterol in C. albicans through three cycles, each requiring two electrons from NADPH-dependent Ncp1.
“Erg11, a cytochrome P450 enzyme, catalyzes the 14-methylation of lanosterol in C. albicans through three cycles13,14, each requiring two electrons from nicotinamide adenine dinucleotide phosphate (NADPH)-dependent Ncp1 reductase15,16.”
From Impairing the interaction between Erg11 and cytochrome P450 reductase Ncp1 enhances azoles’ antifungal activities (2025) · cites this paper as [16]
Section 10 discusses NADPH production in budding yeast, but does not address Erg11, lanosterol conversion in C. albicans, or electron transfer from Ncp1. Searches for those terms and for the claimed three-cycle, two-electron mechanism found no supporting passage in our copy. Page numbers were not available. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 312 · Cited by 178
- Authors
- Bradshaw, P. C.
- Affiliations
- East Tennessee State University (US)
- Corresponding author
- Bradshaw, Patrick C.
- ORCID
- Bradshaw, Patrick C.
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2019-02-27
- Volume
- 11
- Issue
- 3
- Pages
- 504
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC6471790
- OpenAlex
- W2916333363
- Cited by
- 178
- References
- 312
- Citations by year
- 2026: 15 · 2025: 30 · 2024: 24 · 2023: 33 · 2022: 18 · 2021: 29 · 2020: 25 · 2019: 4
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons - East Tennessee State University (East Tennessee State University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (AG059096)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- NADPH, aging, longevity, redox stress, TXNRD2, NAD kinase, glutathione, thioredoxin, lifespan extension, Drosophila
- MeSH terms
- Aging, Animals, Cytoplasm, Gene Expression Regulation, Mitochondria, NADP, Oxidation-Reduction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
