Hormesis and vitagenes in aging and longevity: mitochondrial control and hormonal regulation

2013 ◽  
Vol 16 (2) ◽  
Author(s):  
Carolin Cornelius ◽  
Antonio Graziano ◽  
Edward J. Calabrese ◽  
Vittorio Calabrese
Keyword(s):  
Heat Shock ◽  
Life Span ◽  
Stress Responses ◽  
Hormonal Regulation ◽  
Healthy Aging ◽  
Ovarian Function ◽  
Late Onset ◽  
Patient Treatment ◽  
Average Life Span ◽  
Age Related

AbstractAverage life span has increased because of medical and environmental factors, but maximal life span remains unchanged. Understanding the mechanisms of aging will help to reduce age-related morbidity and facilitate healthy aging. Unlike female menopause, which is accompanied by an abrupt and permanent cessation of ovarian function (both folliculogenesis and estradiol production), male aging does not result in either cessation of testosterone production or infertility. Although the circulating serum testosterone concentration does decline with aging, in most men this decrease is small, resulting in levels that are generally within the normal range. Age-related hypogonadism has been referred to as andropause or late-onset hypogonadism (LOH), with LOH considered to be the most suitable term for this condition. Hormone therapy (HT) trials have caused both apprehension and confusion about the overall risks and benefits associated with HT treatment. During aging, a gradual decline in the potency of the heat shock response occurs, and this may prevent the repair of protein damage. Thus, the interest in developing pharmacological agents capable of inducing stress responses is growing within the broad frame of hormesis, which underlie strategies for optimal patient treatment of numerous diseases. Vitagenes encode for heat shock proteins, thioredoxin, and sirtuin protein systems. Nutritional antioxidants have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. Here, we focus on possible signaling mechanisms involved in the activation of vitagenes resulting in enhanced defense against bioenergetic defects leading to degeneration and cell death with consequent impact on longevity processes.

scholarly journals Inhibition of 11β-HSD1 Ameliorates Cognition and Molecular Detrimental Changes after Chronic Mild Stress in SAMP8 Mice

2021 ◽  
Vol 14 (10) ◽  
pp. 1040
Author(s):  
Dolors Puigoriol-Illamola ◽  
Júlia Companys-Alemany ◽  
Kris McGuire ◽  
Natalie Z. M. Homer ◽  
Rosana Leiva ◽  
...  
Keyword(s):  
Stress Responses ◽  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Cognitive Improvement ◽  
Age Related ◽  
Mtorc1 Signaling ◽  
Cognitive Disturbances ◽  
Samp8 Mice

Impaired glucocorticoid (GC) signaling is a significant factor in aging, stress, and neurodegenerative diseases such as Alzheimer’s disease. Therefore, the study of GC-mediated stress responses to chronic moderately stressful situations, which occur in daily life, is of huge interest for the design of pharmacological strategies toward the prevention of neurodegeneration. To address this issue, SAMP8 mice were exposed to the chronic mild stress (CMS) paradigm for 4 weeks and treated with RL-118, an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor. The inhibition of this enzyme is linked with a reduction in GC levels and cognitive improvement, while CMS exposure has been associated with reduced cognitive performance. The aim of this project was to assess whether RL-118 treatment could reverse the deleterious effects of CMS on cognition and behavioral abilities and to evaluate the molecular mechanisms that compromise healthy aging in SAMP8 mice. First, we confirmed the target engagement between RL-118 and 11β-HSD1. Additionally, we showed that DNA methylation, hydroxymethylation, and histone phosphorylation were decreased by CMS induction, and increased by RL-118 treatment. In addition, CMS exposure caused the accumulation of reactive oxygen species (ROS)-induced damage and increased pro-oxidant enzymes—as well as pro-inflammatory mediators—through the NF-κB pathway and astrogliosis markers, such as GFAP. Of note, these modifications were reversed by 11β-HSD1 inhibition. Remarkably, although CMS altered mTORC1 signaling, autophagy was increased in the SAMP8 RL-118-treated mice. We also showed an increase in amyloidogenic processes and a decrease in synaptic plasticity and neuronal remodeling markers in mice under CMS, which were consequently modified by RL-118 treatment. In conclusion, 11β-HSD1 inhibition through RL-118 ameliorated the detrimental effects induced by CMS, including epigenetic and cognitive disturbances, indicating that GC-excess attenuation shows potential as a therapeutic strategy for age-related cognitive decline and AD.

scholarly journals Electrophysiological Measures of Aging Pharynx Function in C. elegans Reveal Enhanced Organ Functionality in Older, Long-lived Mutants

2017 ◽  
Vol 74 (8) ◽  
pp. 1173-1179 ◽  
Author(s):  
Joshua Coulter Russell ◽  
Nikolay Burnaevskiy ◽  
Bridget Ma ◽  
Miguel Arenas Mailig ◽  
Franklin Faust ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Heat Shock ◽  
Life Span ◽  
Insulin Signaling ◽  
Model System ◽  
Wild Type ◽  
Organ Function ◽  
C Elegans ◽  
Age Related ◽  
The Relationship

Abstract The function of the pharynx, an organ in the model system Caenorhabditis elegans, has been correlated with life span and motility (another measure of health) since 1980. In this study, in order to further understand the relationship between organ function and life span, we measured the age-related decline of the pharynx using an electrophysiological approach. We measured and analyzed electropharyngeograms (EPG) of wild type animals, short-lived hsf-1 mutants, and long-lived animals with genetically decreased insulin signaling or increased heat shock pathway signaling; we recorded a total of 2,478 EPGs from 1,374 individuals. As expected, the long-lived daf-2(e1370) and hsf-1OE(uthIs235) animals maintained pharynx function relatively closer to the youthful state during aging, whereas the hsf-1(sy441) and wild type animals’ pharynx function deviated significantly further from the youthful state at advanced age. Measures of the amount of variation in organ function can act as biomarkers of youthful physiology as well. Intriguingly, the long-lived animals had greater variation in the duration of pharynx contraction at older ages.

scholarly journals Diet and Aging

2012 ◽  
Vol 2012 ◽  
pp. 1-20 ◽  
Author(s):  
Samo Ribarič
Keyword(s):  
Life Span ◽  
Stress Responses ◽  
Food Supplement ◽  
Calorie Intake ◽  
Age Related ◽  
Regulate Cell Growth ◽  
Posttranslational Histone Modifications ◽  
The Individual ◽  
Growth And Aging

Nutrition has important long-term consequences for health that are not only limited to the individual but can be passed on to the next generation. It can contribute to the development and progression of chronic diseases thus effecting life span. Caloric restriction (CR) can extend the average and maximum life span and delay the onset of age-associated changes in many organisms. CR elicits coordinated and adaptive stress responses at the cellular and whole-organism level by modulating epigenetic mechanisms (e.g., DNA methylation, posttranslational histone modifications), signaling pathways that regulate cell growth and aging (e.g., TOR, AMPK, p53, and FOXO), and cell-to-cell signaling molecules (e.g., adiponectin). The overall effect of these adaptive stress responses is an increased resistance to subsequent stress, thus delaying age-related changes and promoting longevity. In human, CR could delay many diseases associated with aging including cancer, diabetes, atherosclerosis, cardiovascular disease, and neurodegenerative diseases. As an alternative to CR, several CR mimetics have been tested on animals and humans. At present, the most promising alternatives to the use of CR in humans seem to be exercise, alone or in combination with reduced calorie intake, and the use of plant-derived polyphenol resveratrol as a food supplement.

scholarly journals Noggin rescues age-related stem cell loss in the brain of senescent mice with neurodegenerative pathology

2018 ◽  
Vol 115 (45) ◽  
pp. 11625-11630 ◽  
Author(s):  
María Díaz-Moreno ◽  
Tomás Armenteros ◽  
Simona Gradari ◽  
Rafael Hortigüela ◽  
Laura García-Corzo ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Late Onset ◽  
Hippocampal Neurogenesis ◽  
Bmp Signaling ◽  
In Vitro Assays ◽  
Age Related ◽  
Samp8 Mice ◽  
The Brain

Increasing age is the greatest known risk factor for the sporadic late-onset forms of neurodegenerative disorders such as Alzheimer’s disease (AD). One of the brain regions most severely affected in AD is the hippocampus, a privileged structure that contains adult neural stem cells (NSCs) with neurogenic capacity. Hippocampal neurogenesis decreases during aging and the decrease is exacerbated in AD, but the mechanistic causes underlying this progressive decline remain largely unexplored. We here investigated the effect of age on NSCs and neurogenesis by analyzing the senescence accelerated mouse prone 8 (SAMP8) strain, a nontransgenic short-lived strain that spontaneously develops a pathological profile similar to that of AD and that has been employed as a model system to study the transition from healthy aging to neurodegeneration. We show that SAMP8 mice display an accelerated loss of the NSC pool that coincides with an aberrant rise in BMP6 protein, enhanced canonical BMP signaling, and increased astroglial differentiation. In vitro assays demonstrate that BMP6 severely impairs NSC expansion and promotes NSC differentiation into postmitotic astrocytes. Blocking the dysregulation of the BMP pathway and its progliogenic effect in vivo by intracranial delivery of the antagonist Noggin restores hippocampal NSC numbers, neurogenesis, and behavior in SAMP8 mice. Thus, manipulating the local microenvironment of the NSC pool counteracts hippocampal dysfunction in pathological aging. Our results shed light on interventions that may allow taking advantage of the brain’s natural plastic capacity to enhance cognitive function in late adulthood and in chronic neurodegenerative diseases such as AD.

scholarly journals Counteracting age-related VEGF signaling insufficiency promotes healthy aging and extends life span

Science ◽  
2021 ◽  
Vol 373 (6554) ◽  
pp. eabc8479
Author(s):  
M. Grunewald ◽  
S. Kumar ◽  
H. Sharife ◽  
E. Volinsky ◽  
A. Gileles-Hillel ◽  
...  
Keyword(s):  
Life Span ◽  
Healthy Aging ◽  
Vascular Diseases ◽  
Tumor Burden ◽  
Multiple Organ ◽  
Vegf Signaling ◽  
Established Risk Factor ◽  
Age Related ◽  
Organ Systems ◽  
And Function

Aging is an established risk factor for vascular diseases, but vascular aging itself may contribute to the progressive deterioration of organ function. Here, we show in aged mice that vascular endothelial growth factor (VEGF) signaling insufficiency, which is caused by increased production of decoy receptors, may drive physiological aging across multiple organ systems. Increasing VEGF signaling prevented age-associated capillary loss, improved organ perfusion and function, and extended life span. Healthier aging was evidenced by favorable metabolism and body composition and amelioration of aging-associated pathologies including hepatic steatosis, sarcopenia, osteoporosis, “inflammaging” (age-related multiorgan chronic inflammation), and increased tumor burden. These results indicate that VEGF signaling insufficiency affects organ aging in mice and suggest that modulating this pathway may result in increased mammalian life span and improved overall health.

scholarly journals Cognition in Healthy Aging

2021 ◽  
Vol 18 (3) ◽  
pp. 962
Author(s):  
Macarena Sánchez-Izquierdo ◽  
Rocío Fernández-Ballesteros
Keyword(s):  
Life Span ◽  
Cognitive Functioning ◽  
Healthy Aging ◽  
Intervention Program ◽  
Later Life ◽  
Cognitive Change ◽  
Individual Variability ◽  
Cross Sectional ◽  
Age Related ◽  
Experimental Trials

The study of cognitive change across a life span, both in pathological and healthy samples, has been heavily influenced by developments in cognitive psychology as a theoretical paradigm, neuropsychology and other bio-medical fields; this alongside the increase in new longitudinal and cohort designs, complemented in the last decades by the evaluation of experimental interventions. Here, a review of aging databases was conducted, looking for the most relevant studies carried out on cognitive functioning in healthy older adults. The aim was to review not only longitudinal, cross-sectional or cohort studies, but also by intervention program evaluations. The most important studies, searching for long-term patterns of stability and change of cognitive measures across a life span and in old age, have shown a great range of inter-individual variability in cognitive functioning changes attributed to age. Furthermore, intellectual functioning in healthy individuals seems to decline rather late in life, if ever, as shown in longitudinal studies where age-related decline of cognitive functioning occurs later in life than indicated by cross-sectional studies. The longitudinal evidence and experimental trials have shown the benefits of aerobic physical exercise and an intellectually engaged lifestyle, suggesting that bio-psycho-socioenvironmental factors concurrently with age predict or determine both positive or negative change or stability in cognition in later life.

The role of attenuated redox and heat shock protein responses in the age-related decline in skeletal muscle mass and function

2017 ◽  
Vol 61 (3) ◽  
pp. 339-348 ◽  
Author(s):  
Anne McArdle ◽  
Malcolm J. Jackson
Keyword(s):  
Skeletal Muscle ◽  
Heat Shock ◽  
Muscle Mass ◽  
Stress Responses ◽  
Redox Regulation ◽  
Experimental Models ◽  
Age Related ◽  
Shock Proteins ◽  
And Function

The loss of muscle mass and weakness that accompanies ageing is a major contributor to physical frailty and loss of independence in older people. A failure of muscle to adapt to physiological stresses such as exercise is seen with ageing and disruption of redox regulated processes and stress responses are recognized to play important roles in theses deficits. The role of redox regulation in control of specific stress responses, including the generation of heat shock proteins (HSPs) by muscle appears to be particularly important and affected by ageing. Transgenic and knockout studies in experimental models in which redox and HSP responses were modified have demonstrated the importance of these processes in maintenance of muscle mass and function during ageing. New data also indicate the potential of these processes to interact with and influence ageing in other tissues. In particular the roles of redox signalling and HSPs in regulation of inflammatory pathways appears important in their impact on organismal ageing. This review will briefly indicate the importance of this area and demonstrate how an understanding of the manner in which redox and stress responses interact and how they may be controlled offers considerable promise as an approach to ameliorate the major functional consequences of ageing of skeletal muscle (and potentially other tissues) in man.

Sign in / Sign up

Export Citation Format

Share Document