Bio-Hacking Better Health—Leveraging Metabolic Biochemistry to Maximise Healthspan

Isabella D. Cooper, Yvoni Kyriakidou, Lucy Petagine, Kurtis Edwards and Bradley T. Elliott 2023. Bio-Hacking Better Health—Leveraging Metabolic Biochemistry to Maximise Healthspan. Antioxidants. 12 (9). https://doi.org/10.3390/antiox12091749

TitleBio-Hacking Better Health—Leveraging Metabolic Biochemistry to Maximise Healthspan
TypeJournal article
AuthorsIsabella D. Cooper, Yvoni Kyriakidou, Lucy Petagine, Kurtis Edwards and Bradley T. Elliott
Abstract

In the pursuit of longevity and healthspan, we are challenged with first overcoming chronic diseases of ageing: cardiovascular disease, hypertension, cancer, dementias, type 2 diabetes mellitus. These are hyperinsulinaemia diseases presented in different tissue types. Hyperinsulinaemia reduces endogenous antioxidants, via increased consumption and reduced synthesis. Hyperinsulinaemia enforces glucose fuelling, consuming 4 NAD+ to produce 2 acetyl moieties; beta-oxidation, ketolysis and acetoacetate consume 2, 1 and 0, respectively. This decreases sirtuin, PARPs and oxidative management capacity, leaving reactive oxygen species to diffuse to the cytosol, upregulating aerobic glycolysis, NF-kB and cell division signalling. Also, oxidising cardiolipin, reducing oxidative phosphorylation (OXPHOS) and apoptosis ability; driving a tumourigenic phenotype. Over time, increasing senescent/pathological cell populations occurs, increasing morbidity and mortality. Beta-hydroxybutyrate, an antioxidant, metabolite and signalling molecule, increases synthesis of antioxidants via preserving NAD+ availability and enhancing OXPHOS capacity. Fasting and ketogenic diets increase ketogenesis concurrently decreasing insulin secretion and demand; hyperinsulinaemia inhibits ketogenesis. Lifestyles that maintain lower insulin levels decrease antioxidant catabolism, additionally increasing their synthesis, improving oxidative stress management and mitochondrial function and, subsequently, producing healthier cells. This supports tissue and organ health, leading to a better healthspan, the first challenge that must be overcome in the pursuit of youthful longevity.

KeywordsROS
NAD+
mitochondria
longevity
ketosis
hyperinsulinaemia
insulin
beta-hydroxybutyrate
antioxidant
ageing
JournalAntioxidants
Journal citation12 (9)
ISSN2076-3921
Year2023
PublisherMDPI
Publisher's version
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.3390/antiox12091749
PubMed ID37760052
Web address (URL)https://doi.org/10.3390/antiox12091749
Publication dates
Published11 Sep 2023

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