Dietary Carbohydrates Impair Healthspan and Promote Mortality

Published on Oct 1, 2017in Cell Metabolism 20.57
· DOI :10.1016/j.cmet.2017.09.011
Meenakshi Ravichandran2
Estimated H-index: 2
(École Polytechnique Fédérale de Lausanne),
Gerald Grandl4
Estimated H-index: 4
Michael Ristow47
Estimated H-index: 47
(École Polytechnique Fédérale de Lausanne)
The prospective cohort study, named PURE, found that in >135,000 participants from 18 countries, nutritive carbohydrates increase human mortality, whereas dietary fat reduces it, requesting a fundamental change of current nutritional guidelines. Experimental evidence from animal models provides synergizing mechanistic concepts as well as pharmacological options to mimic low-carb or ketogenic diets.
  • References (10)
  • Citations (1)
Published on Feb 1, 2011in Aging Cell 7.63
Susanne Keipert14
Estimated H-index: 14
Anja Voigt11
Estimated H-index: 11
Susanne Klaus39
Estimated H-index: 39
Little is known about how diet and energy metabolism interact in determination of lifespan under ad libitum feeding. From 12 weeks of age until death, male and female wild-type (WT) and transgenic (TG) mice with increased skeletal muscle mitochondrial uncoupling (HSA-mUCP1 mice) were fed one of three different semisynthetic diets differing in macronutrient ratio: control (high-carbohydrate/low-fat-HCLF) and two high-fat diets: high-carbohydrate/high-fat (HCHF), and low-carbohydrate/high-fat (LCH...
38 Citations Source Cite
Published on Jan 1, 1988in Genetics 4.08
David B. Friedman34
Estimated H-index: 34
(University of California, Berkeley),
Thomas E. Johnson1
Estimated H-index: 1
(University of California, Berkeley)
age-1(hx546) is a recessive mutant allele in Caenorhabditis elegans that results in an increase in mean life span averaging 40% and in maximal life span averaging 60% at 20°; at 25° age-1(hx546) averages a 65% increase in mean life span (25.3 days vs. 15.0 days) and a 110% increase in maximum life span (46.2 days vs. 22.0 days for wild-type hermaphrodites). Mutant males also show extended life spans. age-1(hx546) is associated with a 75% decrease in hermaphrodite self-fertility as compared to th...
643 Citations
Published on Aug 1, 2012in European Journal of Epidemiology 7.02
Griffith A. Bell3
Estimated H-index: 3
(University of Washington),
Elizabeth D. Kantor14
Estimated H-index: 14
(University of Washington)
+ 2 AuthorsEmily White78
Estimated H-index: 78
(University of Washington)
Glucosamine and chondroitin are products commonly used by older adults in the US and Europe. There is limited evidence that they have anti-inflammatory properties, which could provide risk reduction of several diseases. However, data on their long-term health effects is lacking. To evaluate whether use of glucosamine and chondroitin are associated with cause-specific and total mortality. Participants (n = 77,510) were members of a cohort study of Washington State (US) residents aged 50–76 years ...
19 Citations Source Cite
Published on Mar 1, 2014in Cell Metabolism 20.57
Samantha M. Solon-Biet12
Estimated H-index: 12
Aisling C. McMahon17
Estimated H-index: 17
(University of Sydney)
+ 15 AuthorsRichard G. Melvin13
Estimated H-index: 13
(University of Helsinki)
The fundamental questions of what represents a macronutritionally balanced diet and how this maintains health and longevity remain unanswered. Here, the Geometric Framework, a state-space nutritional modeling method, was used to measure interactive effects of dietary energy, protein, fat, and carbohydrate on food intake, cardiometabolic phenotype, and longevity in mice fed one of 25 diets ad libitum. Food intake was regulated primarily by protein and carbohydrate content. Longevity and health we...
296 Citations Source Cite
Published on Oct 1, 2007in Cell Metabolism 20.57
Tim J. Schulz23
Estimated H-index: 23
(University of Jena),
Kim Zarse17
Estimated H-index: 17
(University of Jena)
+ 3 AuthorsMichael Ristow47
Estimated H-index: 47
(University of Jena)
Summary Increasing cellular glucose uptake is a fundamental concept in treatment of type 2 diabetes, whereas nutritive calorie restriction increases life expectancy. We show here that increased glucose availability decreases Caenorhabditis elegans life span, while impaired glucose metabolism extends life expectancy by inducing mitochondrial respiration. The histone deacetylase Sir2.1 is found here to be dispensable for this phenotype, whereas disruption of aak-2 , a homolog of AMP-dependent kina...
728 Citations Source Cite
Published on Jul 1, 2002in Nature 41.58
Su Ju Lin5
Estimated H-index: 5
(Massachusetts Institute of Technology),
Matt Kaeberlein51
Estimated H-index: 51
(Massachusetts Institute of Technology)
+ 5 AuthorsLeonard Guarente119
Estimated H-index: 119
(Massachusetts Institute of Technology)
Calorie restriction (CR) extends lifespan in a wide spectrum of organisms and is the only regimen known to lengthen the lifespan of mammals 1-4 . We established a model of CR in budding yeast Saccharomyces cerevisiae. In this system, lifespan can be extended by limiting glucose or by reducing the activity of the glucose-sensing cyclic-AMP-dependent kinase (PKA) 5 . Lifespan extension in a mutant with reduced PKA activity requires Sir2 and NAD (nicotinamide adenine dinucleotide) 5 . In this study...
835 Citations Source Cite
Published on Apr 1, 2014in Aging Cell 7.63
David E. Harrison39
Estimated H-index: 39
Randy Strong41
Estimated H-index: 41
+ 13 AuthorsNancy L. Nadon15
Estimated H-index: 15
(National Institutes of Health)
Four agents — acarbose (ACA), 17-α-estradiol (EST), nordihydroguaiaretic acid (NDGA), and methylene blue (MB) — were evaluated for lifespan effects in genetically heterogeneous mice tested at three sites. Acarbose increased male median lifespan by 22% (P < 0.0001), but increased female median lifespan by only 5% (P = 0.01). This sexual dimorphism in ACA lifespan effect could not be explained by differences in effects on weight. Maximum lifespan (90th percentile) increased 11% (P < 0.001) in male...
122 Citations Source Cite
Published on Dec 1, 2014in Nature Communications 12.35
Sandra Weimer4
Estimated H-index: 4
Josephine Priebs1
Estimated H-index: 1
+ 13 AuthorsAndreas F.H. Pfeiffer66
Estimated H-index: 66
D-Glucosamine (GlcN) is a freely available and commonly used dietary supplement potentially promoting cartilage health in humans, which also acts as an inhibitor of glycolysis. Here we show that GlcN, independent of the hexosamine pathway, extends Caenorhabditis elegans life span by impairing glucose metabolism that activates AMP-activated protein kinase (AMPK/AAK-2) and increases mitochondrial biogenesis. Consistent with the concept of mitohormesis, GlcN promotes increased formation of mitochon...
64 Citations Source Cite
Published on Sep 1, 2017in Cell Metabolism 20.57
Megan N. Roberts1
Estimated H-index: 1
(University of California, Davis),
Marita A. Wallace3
Estimated H-index: 3
(University of California, Davis)
+ 17 AuthorsTrina A. Knotts14
Estimated H-index: 14
(University of California, Davis)
Summary Calorie restriction, without malnutrition, has been shown to increase lifespan and is associated with a shift away from glycolysis toward beta-oxidation. The objective of this study was to mimic this metabolic shift using low-carbohydrate diets and to determine the influence of these diets on longevity and healthspan in mice. C57BL/6 mice were assigned to a ketogenic, low-carbohydrate, or control diet at 12 months of age and were either allowed to live their natural lifespan or tested fo...
40 Citations Source Cite
Published on Nov 1, 2017in The Lancet 53.25
Mahshid Dehghan22
Estimated H-index: 22
(Population Health Research Institute),
Andrew Mente29
Estimated H-index: 29
(McMaster University)
+ 352 AuthorsAnders H. Rosengren83
Estimated H-index: 83
(University of Gothenburg)
Summary Background The relationship between macronutrients and cardiovascular disease and mortality is controversial. Most available data are from European and North American populations where nutrition excess is more likely, so their applicability to other populations is unclear. Methods The Prospective Urban Rural Epidemiology (PURE) study is a large, epidemiological cohort study of individuals aged 35–70 years (enrolled between Jan 1, 2003, and March 31, 2013) in 18 countries with a median fo...
145 Citations Source Cite
  • References (10)
  • Citations (1)
Cited By1
Published on Mar 5, 2019in Frontiers in Genetics 4.15
Alexey Moskalev17
Estimated H-index: 17
(Engelhardt Institute of Molecular Biology),
Zulfiya Guvatova2
Estimated H-index: 2
(Engelhardt Institute of Molecular Biology)
+ 6 AuthorsAnna V. Kudryavtseva16
Estimated H-index: 16
(Engelhardt Institute of Molecular Biology)
Some effects of aging in animals are tissue-specific. In D. melanogaster neuronal overexpression of Gclc increases lifespan and improves certain physiological parameters associated with health benefits such as locomotor activity, circadian rhythmicity and stress resistance. Our previous transcriptomic analyses of Drosophila heads, that are primarily composed of neuronal tissue, revealed the significant changes in expression levels of genes involved in aging-related signaling pathways (Jak-STAT, ...
Source Cite