Ketogenic diet‐induced weight loss occurs independent of housing temperature and is followed by hyperphagia and weight regain after cessation in mice DOI

Alyssa J. Weber,

Kyle D. Medak, Logan K. Townsend

et al.

The Journal of Physiology, Journal Year: 2022, Volume and Issue: 600(21), P. 4677 - 4693

Published: Sept. 9, 2022

Abstract Ketogenic diets (KDs) are a popular tool used for weight management. Studies in mice have demonstrated that KDs reduce food intake, increase energy expenditure and cause loss. These studies were completed at room temperature, condition below the animal's thermal neutral zone which induces stress. As intake sensitive to environmental temperature it is not clear if KD would exert same beneficial effects under conditions. Adherence restrictive poor consequently important examine effects, underlying mechanisms, of cycling from ketogenic an obesogenic diet. The purpose current study was determine housing impacted obese mechanisms driving KD‐induced loss reverse when switched high fat We demonstrate reductions increases expenditure, improvements glucose homeostasis dependent upon temperature. seems be largely explained by caloric while back diet following period feeding leads hyperphagia‐induced gain. Collectively, our results suggest prior findings with fed likely artifact how housed initial changes transitioning or on intake. image Key points rodents Prior preclinical been stress limits clinical translatability Here diet‐induced similar neutrality appear explain large degree Similarly, switching hyperphagia‐mediated gain

Language: Английский

Stress, epigenetics, and aging: Unraveling the intricate crosstalk DOI Creative Commons
Zeming Wu, Jing Qu, Weiqi Zhang

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 84(1), P. 34 - 54

Published: Nov. 13, 2023

Language: Английский

Citations

54
A torpor-like state in mice slows blood epigenetic aging and prolongs healthspan DOI Creative Commons

Lorna Jayne,

Aurora Lavin-Peter,

Julian Roessler

et al.

Nature Aging, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Torpor and hibernation are extreme physiological adaptations of homeotherms associated with pro-longevity effects. Yet the underlying mechanisms how torpor affects aging, whether hypothermic hypometabolic states can be induced to slow aging increase healthspan, remain unknown. Here we demonstrate that activity a spatially defined neuronal population in preoptic area, which has previously been identified as torpor-regulating brain region, is sufficient induce torpor-like state (TLS) mice. Prolonged induction TLS slows epigenetic across multiple tissues improves healthspan. We isolate effects decreased metabolic rate, long-term caloric restriction, core body temperature (Tb) on blood find decelerating effect TLSs mediated by Tb. Taken together, our findings provide novel mechanistic insight into support growing evidence Tb an important mediator processes. Dissecting processes, authors show activation neurons area induces mice These reduced Tb, reinforcing key

Language: Английский

Citations

3
Cold temperature extends longevity and prevents disease-related protein aggregation through PA28γ-induced proteasomes DOI Creative Commons
Hyun Ju Lee,

Hafiza Alirzayeva,

Seda Koyuncu

et al.

Nature Aging, Journal Year: 2023, Volume and Issue: 3(5), P. 546 - 566

Published: April 3, 2023

Abstract Aging is a primary risk factor for neurodegenerative disorders that involve protein aggregation. Because lowering body temperature one of the most effective mechanisms to extend longevity in both poikilotherms and homeotherms, better understanding cold-induced changes can lead converging modifiers pathological Here, we find cold (15 °C) selectively induces trypsin-like activity proteasome Caenorhabditis elegans through PSME-3, worm orthologue human PA28γ/PSME3. This activator required ameliorates age-related deficits degradation. Moreover, PA28γ/PSME-3 diminishes aggregation C. models diseases such as Huntington’s amyotrophic lateral sclerosis. Notably, exposure cells moderate (36 also activates PA28γ/PSME3, reducing disease-related neurodegeneration. Together, our findings reveal beneficial role crosses evolutionary boundaries with potential implications multi-disease prevention.

Language: Английский

Citations

41
Metabolism, homeostasis, and aging DOI
Alibek Moldakozhayev, Vadim N. Gladyshev

Trends in Endocrinology and Metabolism, Journal Year: 2023, Volume and Issue: 34(3), P. 158 - 169

Published: Jan. 20, 2023

Language: Английский

Citations

28
Insulin at the intersection of thermoregulation and glucose homeostasis DOI Creative Commons
Nathan C. Winn, Michael W. Schleh, Jamie N. Garcia

et al.

Molecular Metabolism, Journal Year: 2024, Volume and Issue: 81, P. 101901 - 101901

Published: Feb. 13, 2024

Mammals are protected from changes in environmental temperature by altering energetic processes that modify heat production. Insulin is the dominant stimulus of glucose uptake and metabolism, which fundamental for thermogenic processes. The purpose this work was to determine interaction ambient induced energy expenditure (EE) on insulin sensitivity fluxes. Short-term adaptive responses thermoneutral (TN, ∼28°C) room (laboratory) (RT, ∼22°C) were studied mice. This range does not cause detectable circulating catecholamines or shivering postabsorptive homeostasis maintained. We tested hypothesis a decrease EE occurs with TN causes resistance reduction action reversed upon short term (<12h) transition RT. Insulin-stimulated disposal (Rd) tissue-specific metabolic index assessed combining isotopic tracers hyperinsulinemic-euglycemic clamps. insulin-stimulated Rd both decreased (∼50%) TN-adapted vs RT-adapted When mice switched TN, rapidly decreases reduced ∼50%. RT exhibit rapid increase EE, but whole-body remains at low rates In contrast, whole body glycolytic flux rose EE. higher without increasing blood, rather diverting storage glycolysis. addition adaptations action, 'insulin-independent' brown fat exquisitely sensitive thermoregulation. These results show adjusts non-stressful contribute support compromising homeostasis.

Language: Английский

Citations

9
The Naked Mole-Rat as a Model for Healthy Aging DOI Creative Commons
Kaori Oka, Masanori Yamakawa, Yoshimi Kawamura

et al.

Annual Review of Animal Biosciences, Journal Year: 2022, Volume and Issue: 11(1), P. 207 - 226

Published: Nov. 1, 2022

Naked mole-rats (NMRs, Heterocephalus glaber) are the longest-lived rodents with a maximum life span exceeding 37 years. They exhibit delayed aging phenotype and resistance to age-related functional decline/diseases. Specifically, they do not display increased mortality age, maintain several physiological functions until nearly end of their lifetime, rarely develop cancer Alzheimer's disease. NMRs live in hypoxic environment underground colonies East Africa highly tolerant hypoxia. These unique characteristics have attracted considerable interest from zoological biomedical researchers. This review summarizes previous studies ecology, hypoxia tolerance, longevity/delayed aging, discusses possible mechanisms contributing healthy aging. In addition, we discuss current issues future perspectives fully elucidate underlying diseases NMRs.

Language: Английский

Citations

30
The brain–body energy conservation model of aging DOI
Evan D. Shaulson, Alan A. Cohen, Martin Picard

et al.

Nature Aging, Journal Year: 2024, Volume and Issue: 4(10), P. 1354 - 1371

Published: Oct. 8, 2024

Language: Английский

Citations

7
Unveiling the Longevity Potential of Natural Phytochemicals: A Comprehensive Review of Active Ingredients in Dietary Plants and Herbs DOI Creative Commons
Yu Wang, Xiuling Cao, Jin Yeul

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(45), P. 24908 - 24927

Published: Oct. 31, 2024

Ancient humans used dietary plants and herbs to treat disease pursue eternal life. Today, phytochemicals in have been shown be the active ingredients, some of which antiaging longevity-promoting effects. Here, we summarize 210 herbs, systematically classify them into 8 groups. We found that all groups can categorized six areas regulate organism longevity: ROS levels, nutrient sensing network, mitochondria, autophagy, gut microbiota, lipid metabolism. review role these processes aging molecular mechanism health benefits through phytochemical-mediated regulation. Among these, how promote longevity microbiota metabolism is rarely highlighted field. Our understanding mechanisms based on above aspects may provide a theoretical basis for further development drugs new insights promotion human longevity.

Language: Английский

Citations

7
Effects of ambient temperatures between 5 and 35 °C on energy balance, body mass and body composition in mice DOI Creative Commons
Zhi‐Jun Zhao, Rui Yang, Min Li

et al.

Molecular Metabolism, Journal Year: 2022, Volume and Issue: 64, P. 101551 - 101551

Published: July 20, 2022

Considerable attention is currently focused on the potential to switch brown adipose tissue (BAT), or promote browning of white tissue, elevate energy expenditure and thereby reduce obesity levels. These processes are already known be switched by cold exposure. Yet humans living in colder regions do not show lower levels obesity. This could because shield themselves from external temperatures, resultant changes BAT thermogenesis offset elevated food intake, reductions other components expenditure.We exposed mice 11 different ambient temperatures between 5 35 °C characterized their balance body weight/composition. As it got progressively increased coincident with thyroid hormone activity. Simultaneously, these increases were matched mass remained stable. Nevertheless, within this envelope unchanged there significant composition - sizes liver small intestine, presumably support greater level stored fat maximally providing about 10% total demands.Elevating activity may a valid strategy storage even if overall but mostly as found here, then impacts small.

Language: Английский

Citations

25
Regulators of health and lifespan extension in genetically diverse mice on dietary restriction DOI Creative Commons
Andrea Di Francesco, Andrew Deighan, Lev Litichevskiy

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 28, 2023

Summary Caloric restriction (CR) delays aging and extends healthy lifespan in multiple species. Alternative forms of dietary (DR) such as intermittent fasting (IF) have drawn significant interest a more sustainable regimen, but the landscape longevity-promoting interventions remains largely unexplored. Identifying most robust, efficacious, experimentally tractable modes DR is key to better understanding implementing effective longevity for human healthspan. To that end, we performed an extensive assessment interventions, investigating effects graded levels CR (20% 40%) IF (1 day 2 days per week) on health survival 960 genetically diverse female mice. All extended lifespan, although only significantly reduced mortality doubling time. Notably, did not extend mice with high pre-intervention bodyweight. We carried out phenotyping determine long-term understand mechanisms driving within-diet heterogeneity lifespan. The top predictor was ability maintain bodyweight through periods handling, indicator stress resilience. Additional predictors long include specific changes immune cells, red blood cell distribution width (RDW), retention adiposity late life. found heritable (h = 0.24), genetic background has larger influence than interventions. identified association RDW chromosome 18 explained 4.3% diet-adjusted variation Diet-induced metabolic traits, beneficial, were relatively poor arguing against long-standing notion works by counteracting negative obesity. These findings indicate improving extending are synonymous parameters may be inappropriate endpoints evaluating preclinical models clinical trials.

Language: Английский

Citations

16