Diabetes medications as potential calorie restriction mimetics-a focus on the alpha-glucosidase inhibitor acarbose.
Calorie restriction mimetic
Energy balance
Glucosidase
Macronutrient
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
10
08
2020
accepted:
22
09
2020
pubmed:
3
10
2020
medline:
2
7
2021
entrez:
2
10
2020
Statut:
ppublish
Résumé
The field of aging research has grown rapidly over the last half-century, with advancement of scientific technologies to interrogate mechanisms underlying the benefit of life-extending interventions like calorie restriction (CR). Coincident with this increase in knowledge has been the rise of obesity and type 2 diabetes (T2D), both associated with increased morbidity and mortality. Given the difficulty in practicing long-term CR, a search for compounds (CR mimetics) which could recapitulate the health and longevity benefits without requiring food intake reductions was proposed. Alpha-glucosidase inhibitors (AGIs) are compounds that function predominantly within the gastrointestinal tract to inhibit α-glucosidase and α-amylase enzymatic digestion of complex carbohydrates, delaying and decreasing monosaccharide uptake from the gut in the treatment of T2D. Acarbose, an AGI, has been shown in pre-clinical models to increase lifespan (greater longevity benefits in males), with decreased body weight gain independent of calorie intake reduction. The CR mimetic benefits of acarbose are further supported by clinical findings beyond T2D including the risk for other age-related diseases (e.g., cancer, cardiovascular). Open questions remain regarding the exclusivity of acarbose relative to other AGIs, potential off-target effects, and combination with other therapies for healthy aging and longevity extension. Given the promising results in pre-clinical models (even in the absence of T2D), a unique mechanism of action and multiple age-related reduced disease risks that have been reported with acarbose, support for clinical trials with acarbose focusing on aging-related outcomes and incorporating biological sex, age at treatment initiation, and T2D-dependence within the design is warranted.
Identifiants
pubmed: 33006707
doi: 10.1007/s11357-020-00278-x
pii: 10.1007/s11357-020-00278-x
pmc: PMC8190416
doi:
Substances chimiques
Glycoside Hydrolase Inhibitors
0
Acarbose
T58MSI464G
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1123-1133Subventions
Organisme : NIA NIH HHS
ID : P30 AG050886
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK056336
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK079626
Pays : United States
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