Experimental demonstration of prenatal programming of mitochondrial aerobic metabolism lasting until adulthood

It is increasingly being postulated that among-individual variation in mitochondrial function underlies variation in individual performance (e.g. growth rate) and state of health. Environmental conditions experienced before birth have been suggested to programme postnatal mitochondrial biology, but the hypothesis that early-life conditions induce consistent and long-lasting differences in mitochondrial function among individuals remains mostly untested. We tested this hypothesis in an avian model by experimentally manipulating prenatal conditions (incubation temperature and stability), then measuring mitochondrial aerobic metabolism in blood cells from the same individuals during postnatal growth and at adulthood. Mitochondrial aerobic metabolism changed markedly across life stages, and part of these age-related changes were influenced by the prenatal experimental conditions. A high incubation temperature induced a consistent and long-lasting increase in mitochondrial aerobic metabolism, while unstable incubation conditions had a delayed effect, with an increased metabolism only being observed at adulthood. While we detected significant within-individual consistency in mitochondrial aerobic metabolism across life-stages, the prenatal temperature regime only accounted for a relatively small proportion (<20%) of the consistent among-individual differences we observed. Our results demonstrate that prenatal conditions can program consistent and long-lasting differences in mitochondrial function, which could potentially underly among-individual variation in performance and health state.

Download Full-text

Incubation Temperature Influences the Duration of Egg Hatching and Early Development in the Boreal Digging Frog, Kaloula Borealis

Journal of Zoo Biology ◽

10.33687/zoobiol.003.01.2267 ◽

2020 ◽

Vol 3 (1) ◽

pp. ACCEPTED

Author(s):

Rho-Jeong Rae

Keyword(s):

Water Temperature ◽

Early Life ◽

Rainy Season ◽

Incubation Temperature ◽

Life Stages ◽

Early Life Stages ◽

Egg Hatching ◽

Significant Difference ◽

The Mean ◽

Hatching Rates

This study investigated the boreal digging frog, Kaloula borealis, to determine the egg hatching period and whether the hatching period is affected by incubation temperature. The results of this study showed that all the eggs hatched within 48 h after spawning, with 28.1% (±10.8, n=52) hatching within 24 h and 99.9% (±0.23, n=49) within 48 h after spawning. A significant difference was noted in the mean hatching proportion of tadpoles at different water temperatures. The mean hatching rates between 15 and 24 h after spawning was higher at a water temperature of 21.1 (±0.2) °C than at 24.1 (±0.2) °C. These results suggest that incubation temperature affected the early life stages of the boreal digging frog, since they spawn in ponds or puddles that form during the rainy season.

Download Full-text

Health state utilities in patients with diabetic retinopathy, diabetic macular oedema and age-related macular degeneration: a systematic review

BMC Ophthalmology ◽

10.1186/1471-2415-13-74 ◽

2013 ◽

Vol 13 (1) ◽

Cited By ~ 11

Author(s):

Edith Poku ◽

John Brazier ◽

Jill Carlton ◽

Alberto Ferreira

Keyword(s):

Systematic Review ◽

Diabetic Retinopathy ◽

Macular Degeneration ◽

Macular Oedema ◽

Diabetic Macular Oedema ◽

Age Related Macular Degeneration ◽

Health State ◽

Age Related ◽

Health State Utilities

Download Full-text

Exercise and Mitochondrial Function: Importance and InferenceA Mini Review

Current Molecular Medicine ◽

10.2174/1566524021666211129110542 ◽

2021 ◽

Vol 21 ◽

Author(s):

Vaishali K. ◽

Nitesh Kumar ◽

Vanishree Rao ◽

Rakesh Krishna Kovela ◽

Mukesh Kumar Sinha

Keyword(s):

Skeletal Muscle ◽

Mitochondrial Function ◽

Skeletal Muscles ◽

Muscle Cells ◽

Skeletal Muscle Cells ◽

Present Review ◽

Age Related ◽

Exercise Induced ◽

Mitochondrial Adaptations

: Skeletal muscles must generate and distribute energy properly in order to function perfectly. Mitochondria in skeletal muscle cells form vast networks to meet this need, and their functions may improve as a result of exercise. In the present review, we discussed exercise-induced mitochondrial adaptations, age-related mitochondrial decline, and a biomarker as a mitochondrial function indicator and exercise interference.

Download Full-text

The Intersection of Metformin and Inflammation

AJP Cell Physiology ◽

10.1152/ajpcell.00604.2020 ◽

2021 ◽

Author(s):

Leena P. Bharath ◽

Barbara S. Nikolajczyk

Keyword(s):

Mitochondrial Function ◽

Immune Cells ◽

Immune Cell ◽

Cell Types ◽

Remarkable Effect ◽

Tumor Onset ◽

Age Related ◽

Immune Mediated ◽

Autoimmune Conditions ◽

Near Term

The biguanide metformin is the most commonly used antidiabetic drug. Recent studies show that metformin not only improves chronic inflammation by improving metabolic parameters but also has a direct anti-inflammatory effect. In light of these findings, it is essential to identify the inflammatory pathways targeted by metformin to develop a comprehensive understanding of the mechanisms of action of this drug. Commonly accepted mechanisms of metformin action include AMPK activation and inhibition of mTOR pathways, which are evaluated in multiple diseases. Additionally, metformin's action on mitochondrial function and cellular homeostasis processes such as autophagy, is of particular interest because of the importance of these mechanisms in maintaining cellular health. Both dysregulated mitochondria and failure of the autophagy pathways, the latter of which impair clearance of dysfunctional, damaged, or excess organelles, affect cellular health drastically and can trigger the onset of metabolic and age-related diseases. Immune cells are the fundamental cell types that govern the health of an organism. Thus, dysregulation of autophagy or mitochondrial function in immune cells has a remarkable effect on susceptibility to infections, response to vaccination, tumor onset, and the development of inflammatory and autoimmune conditions. Here we summarize the latest research on metformin's regulation of immune cell mitochondrial function and autophagy as evidence that new clinical trials on metformin with primary outcomes related to the immune system should be considered to treat immune-mediated diseases over the near term.

Download Full-text

The Gut Microbiota and Healthy Aging: A Mini-Review

Gerontology ◽

10.1159/000490615 ◽

2018 ◽

Vol 64 (6) ◽

pp. 513-520 ◽

Cited By ~ 59

Author(s):

Sangkyu Kim ◽

S. Michal Jazwinski

Keyword(s):

Gut Microbiota ◽

Individual Variation ◽

Gut Microbiome ◽

Chronological Age ◽

Low Grade ◽

Beneficial Effects ◽

Gut Dysbiosis ◽

Age Related ◽

Host Health ◽

Nutrient Signaling

The gut microbiota shows a wide inter-individual variation, but its within-individual variation is relatively stable over time. A functional core microbiome, provided by abundant bacterial taxa, seems to be common to various human hosts regardless of their gender, geographic location, and age. With advancing chronological age, the gut microbiota becomes more diverse and variable. However, when measures of biological age are used with adjustment for chronological age, overall richness decreases, while a certain group of bacteria associated with frailty increases. This highlights the importance of considering biological or functional measures of aging. Studies using model organisms indicate that age-related gut dysbiosis may contribute to unhealthy aging and reduced longevity. The gut microbiome depends on the host nutrient signaling pathways for its beneficial effects on host health and lifespan, and gut dysbiosis disrupting the interdependence may diminish the beneficial effects or even have reverse effects. Gut dysbiosis can trigger the innate immune response and chronic low-grade inflammation, leading to many age-related degenerative pathologies and unhealthy aging. The gut microbiota communicates with the host through various biomolecules, nutrient signaling-independent pathways, and epigenetic mechanisms. Disturbance of these communications by age-related gut dysbiosis can affect the host health and lifespan. This may explain the impact of the gut microbiome on health and aging.

Download Full-text

Pathways for urea production during early life of an air-breathing teleost, the African catfish Clarias gariepinus Burchell

Journal of Experimental Biology ◽

10.1242/jeb.204.12.2155 ◽

2001 ◽

Vol 204 (12) ◽

pp. 2155-2165 ◽

Cited By ~ 6

Author(s):

Bendik F. Terjesen ◽

Terry D. Chadwick ◽

Johan A. J. Verreth ◽

Ivar Rønnestad ◽

Patricia A. Wright

Keyword(s):

Early Development ◽

Early Life ◽

Developmental Stages ◽

Clarias Gariepinus ◽

African Catfish ◽

Life Stages ◽

Carbamoyl Phosphate ◽

Experimental Conditions ◽

Air Breathing ◽

Urea Production

SUMMARY Embryos and larvae of the African catfish Clarias gariepinus excrete significant quantities of urea. The present study focused on the potential urea-generating pathways during early development of this teleost; uricolysis, argininolysis and the ornithine–urea cycle (OUC). Uricase, allantoinase, allantoicase and ureidoglycollate lyase of the uricolytic pathway were expressed in all early life stages and in adult liver of C. gariepinus. Uricase activity increased in starved larvae compared with yolk-sac larvae. The key regulatory enzyme of the teleost OUC, carbamoyl phosphate synthetase III (CPSase III), was expressed predominantly in muscle of developing C. gariepinus larvae and showed negligible activity in the absence of its allosteric effector N-acetyl-l-glutamate. CPSase III and ornithine carbamoyl transferase activities increased in fed larvae compared with starved larvae. In contrast to the early developmental stages, adult C. gariepinus expressed only low and variable levels of CPSase III, suggesting that, under the experimental conditions employed, OUC expression is influenced by developmental stage in this species. The data indicate that early C. gariepinus life stages express the enzymes necessary for urea production by uricolysis, argininolysis and the OUC, and this may explain why urea tissue levels and urea excretion rates are substantial during the early development of this air-breathing teleost.

Download Full-text

Older Drivers’ Differential Performance across Hazardous Scenarios

Proceedings of the Human Factors and Ergonomics Society Annual Meeting ◽

10.1177/1071181319631489 ◽

2019 ◽

Vol 63 (1) ◽

pp. 27-31

Author(s):

Jonathan Kasko ◽

HeeSun Choi ◽

Jing Feng

Keyword(s):

Interface Design ◽

Individual Performance ◽

Older Drivers ◽

Group Differences ◽

Attentional Processing ◽

Left Turn ◽

Older Driver ◽

Differential Performance ◽

Driver Performance ◽

Age Related

With age-related changes in cognitive functioning including attention, older drivers experience increased crash risks and are particularly overrepresented in vehicle crashes in driving situations such as making a left turn and merging with traffic. Effective remedies via assessment, training, and interface design require understanding of individual performance in specific scenarios. In this study, we investigated older driver performance characteristics in eight distinct hazard scenarios. Participants completed a task measuring their attentional processing of information and decision at intersections. The findings revealed sizable heteroge-neity in performance across scenarios, with older drivers being more conservative or liberal in certain situa-tions. Some group differences were also observed. These findings suggest the importance of examining individual performance in unique driving scenarios in addition to an aggregated accuracy across all scenar-ios.

Download Full-text

Disparate Central and Peripheral Effects of Circulating IGF-1 Deficiency on Tissue Mitochondrial Function

Molecular Neurobiology ◽

10.1007/s12035-019-01821-4 ◽

2019 ◽

Vol 57 (3) ◽

pp. 1317-1331 ◽

Cited By ~ 2

Author(s):

Gavin Pharaoh ◽

Daniel Owen ◽

Alexander Yeganeh ◽

Pavithra Premkumar ◽

Julie Farley ◽

...

Keyword(s):

Oxidative Stress ◽

Cognitive Function ◽

Spatial Learning ◽

Mitochondrial Function ◽

Coupling Efficiency ◽

Redox Status ◽

Cellular Aging ◽

Age Related ◽

The Brain ◽

Circulating Levels

AbstractAge-related decline in circulating levels of insulin-like growth factor (IGF)-1 is associated with reduced cognitive function, neuronal aging, and neurodegeneration. Decreased mitochondrial function along with increased reactive oxygen species (ROS) and accumulation of damaged macromolecules are hallmarks of cellular aging. Based on numerous studies indicating pleiotropic effects of IGF-1 during aging, we compared the central and peripheral effects of circulating IGF-1 deficiency on tissue mitochondrial function using an inducible liver IGF-1 knockout (LID). Circulating levels of IGF-1 (~ 75%) were depleted in adult male Igf1f/f mice via AAV-mediated knockdown of hepatic IGF-1 at 5 months of age. Cognitive function was evaluated at 18 months using the radial arm water maze and glucose and insulin tolerance assessed. Mitochondrial function was analyzed in hippocampus, muscle, and visceral fat tissues using high-resolution respirometry O2K as well as redox status and oxidative stress in the cortex. Peripherally, IGF-1 deficiency did not significantly impact muscle mass or mitochondrial function. Aged LID mice were insulin resistant and exhibited ~ 60% less adipose tissue but increased fat mitochondrial respiration (20%). The effects on fat metabolism were attributed to increases in growth hormone. Centrally, IGF-1 deficiency impaired hippocampal-dependent spatial acquisition as well as reversal learning in male mice. Hippocampal mitochondrial OXPHOS coupling efficiency and cortex ATP levels (~ 50%) were decreased and hippocampal oxidative stress (protein carbonylation and F2-isoprostanes) was increased. These data suggest that IGF-1 is critical for regulating mitochondrial function, redox status, and spatial learning in the central nervous system but has limited impact on peripheral (liver and muscle) metabolism with age. Therefore, IGF-1 deficiency with age may increase sensitivity to damage in the brain and propensity for cognitive deficits. Targeting mitochondrial function in the brain may be an avenue for therapy of age-related impairment of cognitive function. Regulation of mitochondrial function and redox status by IGF-1 is essential to maintain brain function and coordinate hippocampal-dependent spatial learning. While a decline in IGF-1 in the periphery may be beneficial to avert cancer progression, diminished central IGF-1 signaling may mediate, in part, age-related cognitive dysfunction and cognitive pathologies potentially by decreasing mitochondrial function.

Download Full-text

Differential Effects of Silibinin A on Mitochondrial Function in Neuronal PC12 and HepG2 Liver Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/1652609 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Carsten Esselun ◽

Bastian Bruns ◽

Stephanie Hagl ◽

Rekha Grewal ◽

Gunter P. Eckert

Keyword(s):

Membrane Potential ◽

Oxidative Phosphorylation ◽

Mitochondrial Membrane Potential ◽

Cell Lines ◽

Mitochondrial Function ◽

Mitochondrial Membrane ◽

Nitrosative Stress ◽

Citrate Synthase ◽

Atp Levels ◽

Age Related

The Mediterranean plant Silybum marianum L., commonly known as milk thistle, has been used for centuries to treat liver disorders. The flavonolignan silibinin represents a natural antioxidant and the main bioactive ingredient of silymarin (silybin), a standard extract of its seeds. Mitochondrial dysfunction and the associated generation of reactive oxygen/nitrogen species (ROS/RNS) are involved in the development of chronic liver and age-related neurodegenerative diseases. Silibinin A (SIL A) is one of two diastereomers found in silymarin and was used to evaluate the effects of silymarin on mitochondrial parameters including mitochondrial membrane potential and ATP production with and without sodium nitroprusside- (SNP-) induced nitrosative stress, oxidative phosphorylation, and citrate synthase activity in HepG2 and PC12 cells. Both cell lines were influenced by SIL A, but at different concentrations. SIL A significantly weakened nitrosative stress in both cell lines. Low concentrations not only maintained protective properties but also increased basal mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) levels. However, these effects could not be associated with oxidative phosphorylation. On the other side, high concentrations of SIL A significantly decreased MMP and ATP levels. Although SIL A did not provide a general improvement of the mitochondrial function, our findings show that SIL A protects against SNP-induced nitrosative stress at the level of mitochondria making it potentially beneficial against neurological disorders.

Download Full-text