scholarly journals Nutrients and Pathways that Regulate Health Span and Life Span

Geriatrics ◽  
2020 ◽  
Vol 5 (4) ◽  
pp. 95
Author(s):  
Carla Pignatti ◽  
Stefania D’Adamo ◽  
Claudio Stefanelli ◽  
Flavio Flamigni ◽  
Silvia Cetrullo
Keyword(s):  
Health Status ◽  
Life Span ◽  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Dietary Habits ◽  
Human Life ◽  
Nutrient Sensing ◽  
Model Organisms ◽  
Health Span ◽  
Nutritional Conditions

Both life span and health span are influenced by genetic, environmental and lifestyle factors. With the genetic influence on human life span estimated to be about 20–25%, epigenetic changes play an important role in modulating individual health status and aging. Thus, a main part of life expectance and healthy aging is determined by dietary habits and nutritional factors. Excessive or restricted food consumption have direct effects on health status. Moreover, some dietary interventions including a reduced intake of dietary calories without malnutrition, or a restriction of specific dietary component may promote health benefits and decrease the incidence of aging-related comorbidities, thus representing intriguing potential approaches to improve healthy aging. However, the relationship between nutrition, health and aging is still not fully understood as well as the mechanisms by which nutrients and nutritional status may affect health span and longevity in model organisms. The broad effect of different nutritional conditions on health span and longevity occurs through multiple mechanisms that involve evolutionary conserved nutrient-sensing pathways in tissues and organs. These pathways interacting each other include the evolutionary conserved key regulators mammalian target of rapamycin, AMP-activated protein kinase, insulin/insulin-like growth factor 1 pathway and sirtuins. In this review we provide a summary of the main molecular mechanisms by which different nutritional conditions, i.e., specific nutrient abundance or restriction, may affect health span and life span.

Molecular mechanisms of life- and health-span extension: role of calorie restriction and exercise intervention

2007 ◽  
Vol 32 (5) ◽  
pp. 954-966 ◽  
Author(s):  
Christy S. Carter ◽  
Tim Hofer ◽  
Arnold Y. Seo ◽  
Christian Leeuwenburgh
Keyword(s):  
Life Span ◽  
Calorie Restriction ◽  
Aging Process ◽  
Molecular Mechanisms ◽  
Geriatric Medicine ◽  
Functional Decline ◽  
Intervention Strategies ◽  
Health Span ◽  
Structural Deterioration ◽  
Age Related

The aging process results in a gradual and progressive structural deterioration of biomolecular and cellular compartments and is associated with many pathological conditions, including cardiovascular disease, stroke, Alzheimer’s disease, osteoporosis, sarcopenia, and liver dysfunction. Concomitantly, each of these conditions is associated with progressive functional decline, loss of independence, and ultimately disability. Because disabled individuals require care in outpatient or home care settings, and in light of the social, emotional, and fiscal burden associated with caring for an ever-increasing elderly population, research in geriatric medicine has recently focused on the biological mechanisms that are involved in the progression towards functional decline and disability to better design treatment and intervention strategies. Although not completely understood, the mechanisms underlying the aging process may partly involve inflammatory processes, oxidative damage, mitochondrial dysfunction, and apoptotic tissue degeneration. These hypotheses are based on epidemiological evidence and data from animal models of aging, as well as interventional studies. Findings from these studies have identified possible strategies to decrease the incidence of age-related diseases and delay the aging process. For example, lifelong exercise is known to extend mean life-span, whereas calorie restriction (CR) increases both mean and maximum life-span in a variety of species. Optimal application of these intervention strategies in the elderly may positively affect health-related outcomes and possibly longevity. Therefore, the scope of this article is to (i) provide an interpretation of various theories of aging from a “health-span” perspective; (ii) describe interventional testing in animals (CR and exercise); and (iii) provide a translational interpretation of these data.

scholarly journals Role of endothelial NAD+ deficiency in age-related vascular dysfunction

2019 ◽  
Vol 316 (6) ◽  
pp. H1253-H1266 ◽  
Author(s):  
Anna Csiszar ◽  
Stefano Tarantini ◽  
Andriy Yabluchanskiy ◽  
Priya Balasubramanian ◽  
Tamas Kiss ◽  
...  
Keyword(s):  
Older Adults ◽  
Molecular Mechanisms ◽  
Cardiovascular Health ◽  
Therapeutic Potential ◽  
Vascular Dysfunction ◽  
Model Organisms ◽  
Vascular Aging ◽  
Health Span ◽  
Comprehensive Overview ◽  
Age Related

Age-related alterations in endothelium and the resulting vascular dysfunction critically contribute to a range of pathological conditions associated with old age. To develop therapies rationally that improve vascular health and thereby increase health span and life span in older adults, it will be essential to understand the cellular and molecular mechanisms contributing to vascular aging. Preclinical studies in model organisms demonstrate that NAD+ availability decreases with age in multiple tissues and that supplemental NAD+ precursors can ameliorate many age-related cellular impairments. Here, we provide a comprehensive overview of NAD+-dependent pathways [including the NAD+-using silent information regulator-2-like enzymes and poly(ADP-ribose) polymerase enzymes] and the potential consequences of endothelial NAD+ deficiency in vascular aging. The multifaceted vasoprotective effects of treatments that reverse the age-related decline in cellular NAD+ levels, as well as their potential limitations, are discussed. The preventive and therapeutic potential of NAD+ intermediates as effective, clinically relevant interventions in older adults at risk for ischemic heart disease, vascular cognitive impairment, and other common geriatric conditions and diseases that involve vascular pathologies (e.g., sarcopenia, frailty) are critically discussed. We propose that NAD+ precursors [e.g., nicotinamide (Nam) riboside, Nam mononucleotide, niacin] should be considered as critical components of combination therapies to slow the vascular aging process and increase cardiovascular health span.

scholarly journals Translational Geroscience: Human Models of Healthy Aging and Longevity

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 300-300
Author(s):  
Sofiya Milman
Keyword(s):  
Healthy Aging ◽  
Model Organisms ◽  
Antagonistic Pleiotropy ◽  
Older Individuals ◽  
Ideal Model ◽  
Health Span ◽  
Healthy Older Adults ◽  
Age Related ◽  
Extended Lifespan ◽  
Disease Free

Abstract While insulin like growth factor-1 (IGF-1) is a well-established modulator of aging and longevity in model organisms, its role in humans is less well understood. Previous ambiguities in part have been attributed to cohort characteristics and unawareness of interactions between age and IGF-1. Centenarians have emerged as an ideal model of healthy aging because they delay the onset of age-related diseases and often remain disease free for the duration of their lifespan. In cohorts of centenarians and generally healthy older adults, we demonstrated that reduced IGF-1 is associated with extended lifespan and health-span. Additionally, we confirmed that IGF-1 interacts with age to modify risk in a manner consistent with antagonistic pleiotropy: younger individuals with high IGF-1 are protected from dementia, vascular disease, diabetes, cancer, and osteoporosis, while older individuals do not exhibit IGF-1-associated protection from disease. These findings offer evidence for IGF-1 modulating health-span and lifespan in humans.

scholarly journals Longevity: Lesson from Model Organisms

Genes ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 518 ◽  
Author(s):  
Giusi Taormina ◽  
Federica Ferrante ◽  
Salvatore Vieni ◽  
Nello Grassi ◽  
Antonio Russo ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Economic Effects ◽  
Model Systems ◽  
Model Organisms ◽  
Human Longevity ◽  
Short Lifespan ◽  
Aging Theories ◽  
Aging Mechanisms ◽  
Shed Light

Research on longevity and healthy aging promises to increase our lifespan and decrease the burden of degenerative diseases with important social and economic effects. Many aging theories have been proposed, and important aging pathways have been discovered. Model organisms have had a crucial role in this process because of their short lifespan, cheap maintenance, and manipulation possibilities. Yeasts, worms, fruit flies, or mammalian models such as mice, monkeys, and recently, dogs, have helped shed light on aging processes. Genes and molecular mechanisms that were found to be critical in simple eukaryotic cells and species have been confirmed in humans mainly by the functional analysis of mammalian orthologues. Here, we review conserved aging mechanisms discovered in different model systems that are implicated in human longevity as well and that could be the target of anti-aging interventions in human.

scholarly journals Common Muscle Metabolic Signatures Highlight Arginine and Lysine Metabolism as Potential Therapeutic Targets to Combat Unhealthy Aging

2021 ◽  
Vol 22 (15) ◽  
pp. 7958
Author(s):  
Janina Tokarz ◽  
Gabriele Möller ◽  
Anna Artati ◽  
Simone Huber ◽  
Anja Zeigerer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Nutrient Sensing ◽  
Biological Aging ◽  
Aging Research ◽  
Muscle Health ◽  
Old Mice ◽  
Health Function ◽  
Metabolic Signatures

Biological aging research is expected to reveal modifiable molecular mechanisms that can be harnessed to slow or possibly reverse unhealthy trajectories. However, there is first an urgent need to define consensus molecular markers of healthy and unhealthy aging. Established aging hallmarks are all linked to metabolism, and a ‘rewired’ metabolic circuitry has been shown to accelerate or delay biological aging. To identify metabolic signatures distinguishing healthy from unhealthy aging trajectories, we performed nontargeted metabolomics on skeletal muscles from 2-month-old and 21-month-old mice, and after dietary and lifestyle interventions known to impact biological aging. We hypothesized that common metabolic signatures would highlight specific pathways and processes promoting healthy aging, while revealing the molecular underpinnings of unhealthy aging. Here, we report 50 metabolites that commonly distinguished aging trajectories in all cohorts, including 18 commonly reduced under unhealthy aging and 32 increased. We stratified these metabolites according to known relationships with various aging hallmarks and found the greatest associations with oxidative stress and nutrient sensing. Collectively, our data suggest interventions aimed at maintaining skeletal muscle arginine and lysine may be useful therapeutic strategies to minimize biological aging and maintain skeletal muscle health, function, and regenerative capacity in old age.

Abstract 224: Detoxification versus Healthy Aging: Aryl Hydrocarbon Receptor Deficiency Improves Vessel Functionality and Increases Healthy Lifespan

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Joachim Altschmied ◽  
Anna Eckers ◽  
Sascha Jakob ◽  
Christian Heiss ◽  
Christine Goy ◽  
...  
Keyword(s):  
Life Span ◽  
Aryl Hydrocarbon Receptor ◽  
Knockout Mice ◽  
Healthy Aging ◽  
Human Subjects ◽  
Surrogate Marker ◽  
Health Span ◽  
C Elegans ◽  
Aryl Hydrocarbon ◽  
Age Related

Development of age-associated vascular diseases like atherosclerosis depends not only on genetic predisposition but also on environmental influences. Ligands of the aryl hydrocarbon receptor (AhR), a ubiquitously expressed transcription factor upregulating detoxifying enzymes, like dioxin and benzo[a]pyrene (BaP) have been shown to promote atherosclerosis. Furthermore, recovery of the blood flow after hindlimb ischemia is significantly enhanced in AhR-deficient mice demonstrating increased angiogenesis in the absence of AhR. Thus, there seems to be a link between AhR, vessel functionality and age-related cardiovascular diseases. To investigate the role of the AhR in health span and vessel function, we analyzed AhR-deficient Caenorhabditis elegans, vessel stiffness in AhR-knockout mice and human subjects of different age and with varying levels of AhR expression as well as functional parameters in primary human endothelial cells (EC) after AhR activation. AhR-deficient C. elegans showed not only an extended life span, but also enhanced motility. In AhR-knockout mice, we observed a reduced PWV in both old and young animals, suggesting that AhR impairs vessel function already at young age. Concomitantly, eNOS phosphorylation at serine 1178, a surrogate marker for eNOS activation, was enhanced in aortas of knockout animals. In line with this, the AhR agonist BaP increased an inhibitory phosphorylation on eNOS in EC. Moreover, BaP reduced migration of EC without changes in proliferation or apoptosis, an effect that was reversed by addition of the AhR antagonist 3’methoxy-4’nitroflavone. In human subjects we demonstrated not only a positive correlation between age and pulse wave velocity (PWV), a readout for vessel stiffness, but also between AhR expression in blood cells and PWV, again suggesting a negative impact of AhR on vessel functionality. Our data demonstrate that loss of AhR extends life span as well as health span in C. elegans. Knockout of AhR in mice leads to improvement of vessel functionality by decreasing vessel stiffness. Finally, the PWV in humans positively correlates not only with age but also with the expression of AhR. Thus, AhR expression may be useful as a new predictor of healthy aging from nematodes to humans.

scholarly journals Comparative study of protein aggregation propensity and mutation tolerance between naked mole-rat and mouse

2021 ◽  
Author(s):  
Savandara Besse ◽  
Raphaël Poujol ◽  
Julie G. Hussin
Keyword(s):  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Therapeutic Interventions ◽  
Model Organisms ◽  
Protein Homeostasis ◽  
Aggregation Propensity ◽  
Age Related ◽  
Mole Rat ◽  
Significant Difference ◽  
Naked Mole Rat

The molecular mechanisms of aging and life expectancy have been studied in model organisms with short lifespans. However, long-lived species may provide insights into successful strategies of healthy aging, potentially opening the door for novel therapeutic interventions in age-related diseases. Notably, naked mole-rats, the longest-lived rodent, present attenuated aging phenotypes in comparison to mice. Their resistance toward oxidative stress has been proposed as one hallmark of their healthy aging, suggesting their ability to maintain cell homeostasis, and specifically their protein homeostasis. To identify the general principles behind their protein homeostasis robustness, we compared the aggregation propensity and mutation tolerance of naked mole-rat and mouse orthologous proteins. Our analysis showed no proteome-wide differential effects in aggregation propensity and mutation tolerance between these species, but several subsets of proteins with a significant difference in aggregation propensity. We found an enrichment of proteins with higher aggregation propensity in naked mole-rat involved the inflammasome complex, and in nucleic acid binding. On the other hand, proteins with lower aggregation propensity in naked mole-rat have a significantly higher mutation tolerance compared to the rest of the proteins. Among them, we identified proteins known to be associated with neurodegenerative and age-related diseases. These findings highlight the intriguing hypothesis about the capacity of the naked mole-rat proteome to delay aging through its proteomic intrinsic architecture.

scholarly journals Transcriptomic analyses of the termite, Cryptotermes secundus, reveal a gene network underlying a long lifespan and high fecundity

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Silu Lin ◽  
Jana Werle ◽  
Judith Korb
Keyword(s):  
Life History ◽  
Social Insects ◽  
Social Communication ◽  
Gene Network ◽  
Social Insect ◽  
Nutrient Sensing ◽  
Model Organisms ◽  
Termite Species ◽  
High Fecundity ◽  
Trade Off

AbstractOrganisms are typically characterized by a trade-off between fecundity and longevity. Notable exceptions are social insects. In insect colonies, the reproducing caste (queens) outlive their non-reproducing nestmate workers by orders of magnitude and realize fecundities and lifespans unparalleled among insects. How this is achieved is not understood. Here, we identified a single module of co-expressed genes that characterized queens in the termite species Cryptotermes secundus. It encompassed genes from all essential pathways known to be involved in life-history regulation in solitary model organisms. By manipulating its endocrine component, we tested the recent hypothesis that re-wiring along the nutrient-sensing/endocrine/fecundity axis can account for the reversal of the fecundity/longevity trade-off in social insect queens. Our data from termites do not support this hypothesis. However, they revealed striking links to social communication that offer new avenues to understand the re-modelling of the fecundity/longevity trade-off in social insects.

scholarly journals Daily Lifestyle and Cutaneous Malignancies

2021 ◽  
Vol 22 (10) ◽  
pp. 5227
Author(s):  
Yu Sawada ◽  
Motonobu Nakamura
Keyword(s):  
Cell Carcinoma ◽  
Molecular Mechanisms ◽  
Skin Diseases ◽  
Human Life ◽  
Lifestyle Factors ◽  
Merkel Cell ◽  
Fundamental Part ◽  
Skin Cancers ◽  
Beneficial Impact ◽  
The Relationship

Daily lifestyle is a fundamental part of human life and its influence accumulates daily in the human body. We observe that a good daily lifestyle has a beneficial impact on our health; however, the actual effects of individual daily lifestyle factors on human skin diseases, especially skin cancers, have not been summarized. In this review, we focused on the influence of daily lifestyle on the development of skin cancer and described the detailed molecular mechanisms of the development or regulation of cutaneous malignancies. Several daily lifestyle factors, such as circadian rhythm disruption, smoking, alcohol, fatty acids, dietary fiber, obesity, and ultraviolet light, are known to be associated with the risk of cutaneous malignancies, malignant melanoma, squamous cell carcinoma, basal cell carcinoma, and Merkel cell carcinoma. Although the influence of some daily lifestyles on the risk of skin cancers is controversial, this review provides us a better understanding of the relationship between daily lifestyle factors and skin cancers.

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