scholarly journals The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver

2021 ◽  
Vol 22 (4) ◽  
pp. 1665
Author(s):  
Guglielmina Chimienti ◽  
Anna Picca ◽  
Flavio Fracasso ◽  
Francesco Russo ◽  
Antonella Orlando ◽  
...  
Keyword(s):  
Calorie Restriction ◽  
Citrate Synthase ◽  
Aging Effect ◽  
Mtdna Damage ◽  
Mitochondrial Markers ◽  
Age Related ◽  
Efficacious Treatment ◽  
Mtdna Deletion ◽  
Cyt C ◽  
Ad Libitum

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.

scholarly journals Calorie restriction leads to greater Akt2 activity and glucose uptake by insulin-stimulated skeletal muscle from old rats

2016 ◽  
Vol 310 (5) ◽  
pp. R449-R458 ◽  
Author(s):  
Haiyan Wang ◽  
Edward B. Arias ◽  
Gregory D. Cartee
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Calorie Restriction ◽  
Akt Inhibitor ◽  
Muscle Insulin Resistance ◽  
Skeletal Muscle Insulin Resistance ◽  
Age Related ◽  
Old Rats ◽  
Ad Libitum ◽  
New Evidence

Skeletal muscle insulin resistance is associated with many common age-related diseases, but moderate calorie restriction (CR) can substantially elevate glucose uptake by insulin-stimulated skeletal muscle from both young and old rats. The current study evaluated the isolated epitrochlearis muscle from ∼24.5-mo-old rats that were either fed ad libitum (AL) or subjected to CR (consuming ∼65% of ad libitum, AL, intake beginning at ∼22.5 mo old). Some muscles were also incubated with MK-2206, a potent and selective Akt inhibitor. The most important results were that in isolated muscles, CR vs. AL resulted in 1) greater insulin-stimulated glucose uptake 2) that was accompanied by significantly increased insulin-mediated activation of Akt2, as indicated by greater phosphorylation on both Thr309and Ser474along with greater Akt2 activity, 3) concomitant with enhanced phosphorylation of several Akt substrates, including an Akt substrate of 160 kDa on Thr642and Ser588, filamin C on Ser2213and proline-rich Akt substrate of 40 kDa on Thr246, but not TBC1D1 on Thr596; and 4) each of the CR effects was eliminated by MK-2206. These data provide compelling new evidence linking greater Akt2 activation to the CR-induced elevation of insulin-stimulated glucose uptake by muscle from old animals.

scholarly journals THE INFLUENCE OF LIFE-EXTENDING MUTATION AND DIETARY INTERVENTION ON GUT MICROBIOTA

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S834-S834
Author(s):  
Michal Masternak ◽  
Denise S Wiesenborn ◽  
Augusto Schneider ◽  
Till Strowig ◽  
Karl –Herbert Schafer ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Calorie Restriction ◽  
Dietary Intervention ◽  
Ecological System ◽  
Gastrointestinal Microbiota ◽  
Age Related ◽  
Ames Dwarf ◽  
Feeding Regimen ◽  
Ad Libitum ◽  
The Impact

Abstract The gastrointestinal microbiota represents a large and complex ecological system of different microorganisms. Recently, there is an increasing interest in the impact of microbiota on development of different age-related diseases. We tested the changes of gut microbiota during development in long-living Ames dwarf (df/df) mice and we compared the effects of this life-extending mutation with the impact of calorie restriction (CR). Importantly, the analysis of microbiome showed significant differences in the ratio of Bacteroidetes and Firmicutes when comparing df/df and normal (N) mice (p<0.001). The LefSe analysis showed distinct microbiome distribution between CR and ad libitum (AL) feeding regimen in N animals (p<0.004), yet there was lack of similar changes in response to CR in df/df mice. In summary, our study showed significant genotype impact on gut microbiota and we showed that life-extending CR regimen provide divergent effects on gut microbiota in N when comparing with df/df mice.

scholarly journals Effects of moderate sleep restriction during 8-week calorie restriction on lipoprotein particles and glucose metabolism

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Joshua R Sparks ◽  
Ryan R Porter ◽  
Shawn D Youngstedt ◽  
Kimberly P Bowyer ◽  
J Larry Durstine ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Calorie Restriction ◽  
Sleep Restriction ◽  
Lipoprotein Subclass ◽  
Cohen’S D ◽  
Time Interaction ◽  
Group Time ◽  
Female Body Mass ◽  
Ad Libitum ◽  
Cohen's D

Abstract Study Objectives This study examined how glucose, glucose regulatory hormones, insulin sensitivity, and lipoprotein subclass particle concentrations and sizes change with sleep restriction during weight loss elicited by calorie restriction. Methods Overweight or obese adults were randomized into an 8-week calorie restriction intervention alone (CR, n = 12; 75% female; body mass index = 31.4 ± 2.9 kg/m2) or combined with sleep restriction (CR+SR, n = 16; 75% female; body mass index = 34.5 ± 3.1 kg/m2). Participants in both groups were given the same instructions to reduce calorie intake. Those in the CR+SR group were instructed to reduce their habitual time-in-bed by 30–90 minutes 5 days each week with 2 ad libitum sleep days. Fasting venous blood samples were collected at pre- and post-intervention. Results Differential changes were found between the two groups (p = 0.028 for group × time interaction) in glucagon concentration, which decreased in the CR group (p = 0.016) but did not change in CR+SR group. Although changes in mean HDL particle (HDL-P) size and visfatin concentration were not statistically different between groups (p = 0.066 and 0.066 for group×time interaction, respectively), mean HDL-P size decreased only in the CR+SR group (Cohen’s d = 0.50, p = 0.022); visfatin concentrations did not change significantly in either group but appeared to decrease in the CR group (Cohen’s d = 0.67, p = 0.170) but not in the CR+SR group (Cohen’s d = 0.43, p = 0.225). Conclusion These results suggest that moderate sleep restriction, despite the presence of periodic ad libitum sleep, influences lipoprotein subclass particles and glucose regulation in individuals undergoing calorie restriction. Clinical trial registration: ClinicalTrials.gov (NCT02413866, Weight Outlooks by Restriction of Diet and Sleep)

scholarly journals Lifelong Calorie Restriction Alleviates Age-Related Oxidative Damage in Peripheral Nerves

2010 ◽  
Vol 13 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Katherine Opalach ◽  
Sunitha Rangaraju ◽  
Irina Madorsky ◽  
Christiaan Leeuwenburgh ◽  
Lucia Notterpek
Keyword(s):  
Oxidative Damage ◽  
Calorie Restriction ◽  
Peripheral Nerves ◽  
Age Related

Aging effect on myeloperoxidase in rat kidney and its modulation by calorie restriction

2005 ◽  
Vol 39 (3) ◽  
pp. 283-289 ◽  
Author(s):  
Tae Gen Son ◽  
Yani Zou ◽  
Byung Pal Yu ◽  
Jaewon Lee ◽  
Hae Young Chung
Keyword(s):  
Calorie Restriction ◽  
Rat Kidney ◽  
Aging Effect

SGLT2 inhibitors as calorie restriction-mimetics: insights on longevity pathways and age-related diseases

Endocrinology ◽  
2021 ◽  
Author(s):  
Caroline W S Hoong ◽  
Marvin W J Chua
Keyword(s):  
Calorie Restriction ◽  
Stress Resistance ◽  
Target Genes ◽  
Metabolic Diseases ◽  
Vascular Inflammation ◽  
Sglt2 Inhibitors ◽  
Acid Oxidation ◽  
The Metabolic Syndrome ◽  
Age Related ◽  
Energy Deprivation

Abstract SGLT2 inhibitors induce glycosuria, reduce insulin levels, promote fatty acid oxidation and ketogenesis. By promoting a nutrient deprivation state, SGLT2 inhibitors upregulate the energy deprivation sensors AMPK and SIRT1, inhibit the nutrient sensors mTOR and insulin/IGF-1, and modulate the closely-linked HIF-2α/HIF-1α pathways. Phosphorylation of AMPK and upregulation of adiponectin and PPAR-α favour a reversal of the metabolic syndrome which have been linked to suppression of chronic inflammation. Downregulation of insulin/IGF1 pathways and mTOR signalling from a reduction in glucose and circulating amino acids promote cellular repair mechanisms including autophagy and proteostasis which confer cellular stress resistance and attenuate cellular senescence. SIRT1, another energy sensor activated by NAD+ in nutrient-deficient states, is reciprocally activated by AMPK, and can deacetylate and activate transcription factors such as PCG-1α, TFAM and NRF2 that regulate mitochondrial biogenesis. FOXO3 transcription factor which target genes in stress resistance, is also activated by AMPK and SIRT1. Modulation of these pathways by SGLT2 inhibitors have been shown to alleviate metabolic diseases, attenuate vascular inflammation and arterial stiffness, improve mitochondrial function and reduce oxidative stress-induced tissue damage. Compared to other calorie restriction mimetics such as metformin, rapamycin, resveratrol and NAD+ precursors, SGLT2 inhibitors appear to be the most promising in the treatment of ageing-related diseases, due to its regulation of multiple longevity pathways that closely resemble that achieved by calorie restriction, and their established efficacy in reduction in cardiovascular events and all-cause mortality. Evidence is compelling for the role of SGLT2 inhibitors as a calorie restriction mimetic in anti-ageing therapeutics.

Muscle metabolism during exercise in young and older untrained and endurance-trained men

1993 ◽  
Vol 75 (5) ◽  
pp. 2125-2133 ◽  
Author(s):  
A. R. Coggan ◽  
A. M. Abduljalil ◽  
S. C. Swanson ◽  
M. S. Earle ◽  
J. W. Farris ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Muscle Mass ◽  
Citrate Synthase ◽  
Metabolic Response ◽  
Plantar Flexion ◽  
Muscle Metabolism ◽  
Resonance Spectroscopy ◽  
Age Related ◽  
Rate Of Increase ◽  
Response To Exercise

To examine effects of aging and endurance training on human muscle metabolism during exercise, 31P magnetic resonance spectroscopy was used to study the metabolic response to exercise in young (21–33 yr) and older (58–68 yr) untrained and endurance-trained men (n = 6/group). Subjects performed graded plantar flexion exercise with the right leg, with metabolic responses measured using a 31P surface coil placed over the lateral head of the gastrocnemius muscle. Muscle biopsy samples were also obtained for determination of citrate synthase activity. Rate of increase in P(i)-to-phosphocreatine ratio with increasing power output was greater (P < 0.01) in older untrained [0.058 +/- 0.022 (SD) W-1] and trained men (0.042 +/- 0.010 W-1) than in young untrained (0.038 +/- 0.017 W-1) and trained men (0.024 +/- 0.010 W-1). Plantar flexor muscle cross-sectional area and volume (determined using 1H magnetic resonance imaging) were 11–12% (P < 0.05) and 16–18% (P < 0.01) smaller, respectively, in older men. When corrected for this difference in muscle mass, age-related differences in metabolic response to exercise were reduced by approximately 50% but remained significant (P < 0.05). Citrate synthase activity was approximately 20% lower (P < 0.001) in older untrained and trained men than in corresponding young groups and was inversely related to P(i)-phosphocreatine slope (r = -0.63, P < 0.001). Age-related reductions in exercise capacity were associated with an altered muscle metabolic response to exercise, which appeared to be due to smaller muscle mass and lower muscle respiratory capacity of older subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Age-related differences in binaural masking level differences: behavioral and electrophysiological evidence

2018 ◽  
Vol 120 (6) ◽  
pp. 2939-2952 ◽  
Author(s):  
Samira Anderson ◽  
Robert Ellis ◽  
Julie Mehta ◽  
Matthew J. Goupell
Keyword(s):  
Aging Effect ◽  
Normal Hearing ◽  
Behavioral Experiment ◽  
Spatial Cues ◽  
Sound Sources ◽  
Frequency Following Response ◽  
Binaural Processing ◽  
Threshold Difference ◽  
Age Related ◽  
Effects Of Aging

The effects of aging and stimulus configuration on binaural masking level differences (BMLDs) were measured behaviorally and electrophysiologically, using the frequency-following response (FFR) to target brainstem/midbrain encoding. The tests were performed in 15 younger normal-hearing (<30 yr) and 15 older normal-hearing (>60 yr) participants. The stimuli consisted of a 500-Hz target tone embedded in a narrowband (50-Hz bandwidth) or wideband (1,500-Hz bandwidth) noise masker. The interaural phase conditions included NoSo (tone and noise presented interaurally in-phase), NoSπ (noise presented interaurally in-phase and tone presented out-of-phase), and NπSo (noise presented interaurally out-of-phase and tone presented in-phase) configurations. In the behavioral experiment, aging reduced the magnitude of the BMLD. The magnitude of the BMLD was smaller for the NoSo–NπSo threshold difference compared with the NoSo–NoSπ threshold difference, and it was also smaller in narrowband compared with wideband conditions, consistent with previous measurements. In the electrophysiology experiment, older participants had reduced FFR magnitudes and smaller differences between configurations. There were significant changes in FFR magnitude between the NoSo to NoSπ configurations but not between the NoSo to NπSo configurations. The age-related reduction in FFR magnitudes suggests a temporal processing deficit, but no correlation was found between FFR magnitudes and behavioral BMLDs. Therefore, independent mechanisms may be contributing to the behavioral and neural deficits. Specifically, older participants had higher behavioral thresholds than younger participants for the NoSπ and NπSo configurations but had equivalent thresholds for the NoSo configuration. However, FFR magnitudes were reduced in older participants across all configurations. NEW & NOTEWORTHY Behavioral and electrophysiological testing reveal an aging effect for stimuli presented in wideband and narrowband noise conditions, such that behavioral binaural masking level differences and subcortical spectral magnitudes are reduced in older compared with younger participants. These deficits in binaural processing may limit the older participant's ability to use spatial cues to understand speech in environments containing competing sound sources.

Effect of calorie restriction on in vivo glucose metabolism by individual tissues in rats

1999 ◽  
Vol 276 (4) ◽  
pp. E728-E738 ◽  
Author(s):  
Thomas J. Wetter ◽  
Annie C. Gazdag ◽  
David J. Dean ◽  
Gregory D. Cartee
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Calorie Restriction ◽  
The Other ◽  
Index Formula ◽  
Tracer Technique ◽  
Ad Libitum ◽  
White Fat ◽  
Fat Pads

We evaluated the effects of 8 mo of calorie restriction [CR: 60% of ad libitum (AL) food intake] on glucose uptake by 14 tissues in unanesthetized, adult (12 mo) F344×BN rats. Glucose metabolism was assessed by the 2-[3H]deoxyglucose tracer technique at 1500 or 2100. Despite an ∼60% decline in insulinemia with CR, plasma 2-[3H]deoxyglucose clearance for CR was greater than for AL at both times. A small, CR-related decrease in glucose metabolic index ([Formula: see text]) occurred only at 1500 in the spleen and heart, and this decrease was reversed at 2100. In some tissues (cerebellum, lung, kidney, soleus, and diaphragm),[Formula: see text] was unaffected by diet, regardless of time. In the other tissues (brown fat, 3 white fat pads, epitrochlearis, plantaris, and gastrocnemius),[Formula: see text] was higher or tended to be higher for CR vs. AL at one or both times. These findings indicate that 8 mo of CR did not cause a continuous reduction in in vivo glucose uptake by any tissue studied, and, in several insulin-sensitive tissues, glucose uptake was at times greater for CR vs. AL rats.

Acute stress response modified by modest inhibition of growth hormone axis: A potential machinery of the anti-aging effect of calorie restriction

2011 ◽  
Vol 132 (3) ◽  
pp. 103-109 ◽  
Author(s):  
Toshimitsu Komatsu ◽  
Lucas S. Trindade ◽  
Takuya Chiba ◽  
Hiroko Hayashi ◽  
Tomoko Henmi ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Stress Response ◽  
Calorie Restriction ◽  
Acute Stress ◽  
Aging Effect ◽  
Inhibition Of Growth ◽  
Acute Stress Response
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