scholarly journals Implications of NAD+ Metabolism in the Aging Retina and Retinal Degeneration

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Ravirajsinh N. Jadeja ◽  
Menaka C. Thounaojam ◽  
Manuela Bartoli ◽  
Pamela M. Martin
Keyword(s):  
Nad Metabolism ◽  
Age Related ◽  
Promising Therapeutic Target ◽  
Organ Systems ◽  
Age Dependent ◽  
The Subject ◽  
Mitochondrial Oxidative Damage ◽  
And Function ◽  
Visual Health

Nicotinamide adenine dinucleotide (NAD+) plays an important role in various key biological processes including energy metabolism, DNA repair, and gene expression. Accumulating clinical and experimental evidence highlights an age-dependent decline in NAD+ levels and its association with the development and progression of several age-related diseases. This supports the establishment of NAD+ as a critical regulator of aging and longevity and, relatedly, a promising therapeutic target to counter adverse events associated with the normal process of aging and/or the development and progression of age-related disease. Relative to the above, the metabolism of NAD+ has been the subject of numerous investigations in various cells, tissues, and organ systems; however, interestingly, studies of NAD+ metabolism in the retina and its relevance to the regulation of visual health and function are comparatively few. This is surprising given the critical causative impact of mitochondrial oxidative damage and bioenergetic crises on the development and progression of degenerative disease of the retina. Hence, the role of NAD+ in this tissue, normally and aging and/or disease, should not be ignored. Herein, we discuss important findings in the field of NAD+ metabolism, with particular emphasis on the importance of the NAD+ biosynthesizing enzyme NAMPT, the related metabolism of NAD+ in the retina, and the consequences of NAMPT and NAD+ deficiency or depletion in this tissue in aging and disease. We discuss also the implications of potential therapeutic strategies that augment NAD+ levels on the preservation of retinal health and function in the above conditions. The overarching goal of this review is to emphasize the importance of NAD+ metabolism in normal, aging, and/or diseased retina and, by so doing, highlight the necessity of additional clinical studies dedicated to evaluating the therapeutic utility of strategies that enhance NAD+ levels in improving vision.

scholarly journals Role of Age-Related Mitochondrial Dysfunction in Sarcopenia

2020 ◽  
Vol 21 (15) ◽  
pp. 5236 ◽  
Author(s):  
Evelyn Ferri ◽  
Emanuele Marzetti ◽  
Riccardo Calvani ◽  
Anna Picca ◽  
Matteo Cesari ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cellular Senescence ◽  
Significant Loss ◽  
Muscle Aging ◽  
Age Related ◽  
Mitochondrial Functions ◽  
Health Quality ◽  
Skeletal Muscle Aging ◽  
And Function

Skeletal muscle aging is associated with a significant loss of skeletal muscle strength and power (i.e., dynapenia), muscle mass and quality of life, a phenomenon known as sarcopenia. This condition affects nearly one-third of the older population and is one of the main factors leading to negative health outcomes in geriatric patients. Notwithstanding the exact mechanisms responsible for sarcopenia are not fully understood, mitochondria have emerged as one of the central regulators of sarcopenia. In fact, there is a wide consensus on the assumption that the loss of mitochondrial integrity in myocytes is the main factor leading to muscle degeneration. Mitochondria are also key players in senescence. It has been largely proven that the modulation of mitochondrial functions can induce the death of senescent cells and that removal of senescent cells improves musculoskeletal health, quality, and function. In this review, the crosstalk among mitochondria, cellular senescence, and sarcopenia will be discussed with the aim to elucidate the role that the musculoskeletal cellular senescence may play in the onset of sarcopenia through the mediation of mitochondria.

scholarly journals Aging Science Talks: The role of miR-181a in age-related loss of muscle mass and function

2020 ◽  
Vol 4 ◽  
pp. 81-85
Author(s):  
Maria Borja-Gonzalez ◽  
Jose C. Casas-Martinez ◽  
Brian McDonagh ◽  
Katarzyna Goljanek-Whysall
Keyword(s):  
Muscle Mass ◽  
Age Related ◽  
And Function

scholarly journals Thrombospondin-1 in maladaptive aging responses: a concept whose time has come

2020 ◽  
Vol 319 (1) ◽  
pp. C45-C63
Author(s):  
Jeffrey S. Isenberg ◽  
David D. Roberts
Keyword(s):  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Genotoxic Stress ◽  
Cell Types ◽  
Cellular Tissue ◽  
Therapeutic Agents ◽  
Age Related ◽  
Organ Systems ◽  
Age Dependent ◽  
Thrombospondin 1

Numerous age-dependent alterations at the molecular, cellular, tissue and organ systems levels underlie the pathophysiology of aging. Herein, the focus is upon the secreted protein thrombospondin-1 (TSP1) as a promoter of aging and age-related diseases. TSP1 has several physiological functions in youth, including promoting neural synapse formation, mediating responses to ischemic and genotoxic stress, minimizing hemorrhage, limiting angiogenesis, and supporting wound healing. These acute functions of TSP1 generally require only transient expression of the protein. However, accumulating basic and clinical data reinforce the view that chronic diseases of aging are associated with accumulation of TSP1 in the extracellular matrix, which is a significant maladaptive contributor to the aging process. Identification of the relevant cell types that chronically produce and respond to TSP1 and the molecular mechanisms that mediate the resulting maladaptive responses could direct the development of therapeutic agents to delay or revert age-associated maladies.

scholarly journals Propensity of undulatory swimmers, such as worms, to go against the flow

2015 ◽  
Vol 112 (12) ◽  
pp. 3606-3611 ◽  
Author(s):  
Jinzhou Yuan ◽  
David M. Raizen ◽  
Haim H. Bau
Keyword(s):  
Control Strategies ◽  
Aquatic Organisms ◽  
Life Cycles ◽  
Environmental Cues ◽  
Mechanical Forces ◽  
C Elegans ◽  
The Subject ◽  
And Function ◽  
First Time

The ability to orient oneself in response to environmental cues is crucial to the survival and function of diverse organisms. One such orientation behavior is the alignment of aquatic organisms with (negative rheotaxis) or against (positive rheotaxis) fluid current. The questions of whether low-Reynolds-number, undulatory swimmers, such as worms, rheotax and whether rheotaxis is a deliberate or an involuntary response to mechanical forces have been the subject of conflicting reports. To address these questions, we use Caenorhabditis elegans as a model undulatory swimmer and examine, in experiment and theory, the orientation of C. elegans in the presence of flow. We find that when close to a stationary surface the animal aligns itself against the direction of the flow. We elucidate for the first time to our knowledge the mechanisms of rheotaxis in worms and show that rheotaxis can be explained solely by mechanical forces and does not require sensory input or deliberate action. The interaction between the flow field induced by the swimmer and a nearby surface causes the swimmer to tilt toward the surface and the velocity gradient associated with the flow rotates the animal to face upstream. Fluid mechanical computer simulations faithfully mimic the behavior observed in experiments, supporting the notion that rheotaxis behavior can be fully explained by hydrodynamics. Our study highlights the important role of hydrodynamics in the behavior of small undulating swimmers and may assist in developing control strategies to affect the animals’ life cycles.

Age-dependent alterations in Ca2+ homeostasis: role of TRPV5 and TRPV6

2006 ◽  
Vol 291 (6) ◽  
pp. F1177-F1183 ◽  
Author(s):  
Monique van Abel ◽  
Sylvie Huybers ◽  
Joost G. J. Hoenderop ◽  
Annemiete W. C. M. van der Kemp ◽  
Johannes P. T. M. van Leeuwen ◽  
...  
Keyword(s):  
Vitamin D ◽  
Mrna Levels ◽  
Serum Osteocalcin ◽  
Intestinal Epithelial ◽  
Receptor Mrna ◽  
Age Related ◽  
Age Dependent ◽  
Elder People ◽  
Age Related Changes

Aging is associated with alterations in Ca2+ homeostasis, which predisposes elder people to hyperparathyroidism and osteoporosis. Intestinal Ca2+ absorption decreases with aging and, in particular, active transport of Ca2+ by the duodenum. In addition, there are age-related changes in renal Ca2+ handling. To examine age-related changes in expression of the renal and intestinal epithelial Ca2+ channels, control (TRPV5+/+) and TRPV5 knockout (TRPV5−/−) mice aged 10, 30, and 52 wk were studied. Aging of TRPV5+/+ mice resulted in a tendency toward increased renal Ca2+ excretion and significantly decreased intestinal Ca2+ absorption, which was accompanied by reduced expression of TRPV5 and TRPV6, respectively, despite increased serum 1,25(OH)2D3 levels. Similarly, in TRPV5−/− mice the existing renal Ca2+ loss was more pronounced in elder animals, whereas the compensatory intestinal Ca2+ absorption and TRPV6 expression declined with aging. In both mice strains, aging resulted in a resistance to 1,25(OH)2D3 and diminished renal vitamin D receptor mRNA levels, whereas serum Ca2+ levels remained constant. Furthermore, 52-wk-old TRPV5−/− mice showed severe hyperparathyroidism, whereas PTH levels in elder TRPV5+/+ mice remained normal. In 52-wk-old TRPV5−/− mice, serum osteocalcin levels were increased in accordance with the elevated PTH levels, suggesting an increased bone turnover in these mice. In conclusion, downregulation of TRPV5 and TRPV6 is likely involved in the impaired Ca2+ (re)absorption during aging. Moreover, TRPV5−/− mice likely develop age-related hyperparathyroidism and osteoporotic characteristics before TRPV5+/+ mice, demonstrating the importance of the epithelial Ca2+ channels in Ca2+ homeostasis.

scholarly journals Age-Dependent Decline of NAD+ - Universal Truth or Confounded Consensus?

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 101
Author(s):  
A. Augusto Peluso ◽  
Mads V. Damgaard ◽  
Marcelo A. S. Mori ◽  
Jonas T. Treebak
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Electron Transport Chain ◽  
Cell Type ◽  
Nad Metabolism ◽  
C Elegans ◽  
Age Related ◽  
Transport Chain ◽  
Age Dependent ◽  
Metabolic Reactions ◽  
Universal Truth

Nicotinamide adenine dinucleotide (NAD+) is an essential molecule involved in various metabolic reactions, acting as an electron donor in the electron transport chain and as a co-factor for NAD+-dependent enzymes. In the early 2000s, reports that NAD+ declines with aging introduced the notion that NAD+ metabolism is globally and progressively impaired with age. Since then, NAD+ became an attractive target for potential pharmacological therapies aiming to increase NAD+ levels to promote vitality and protect against age-related diseases. This review summarizes and discusses a collection of studies that report the levels of NAD+ with aging in different species (i.e., yeast, C. elegans, rat, mouse, monkey, and human), to determine whether the notion that overall NAD+ levels decrease with aging stands true. We find that, despite systematic claims of overall changes in NAD+ levels with aging, the evidence to support such claims is very limited and often restricted to a single tissue or cell type. This is particularly true in humans, where the development of NAD+ levels during aging is still poorly characterized. There is a need for much larger, preferably longitudinal, studies to assess how NAD+ levels develop with aging in various tissues. This will strengthen our conclusions on NAD metabolism during aging and should provide a foundation for better pharmacological targeting of relevant tissues.

scholarly journals Impaired peroxisomal import in Drosophila hepatocyte-like cells induces cardiac dysfunction through the pro-inflammatory cytokine Upd3

2019 ◽  
Author(s):  
Kerui Huang ◽  
Ting Miao ◽  
Kai Chang ◽  
Ping Kang ◽  
Qiuhan Jiang ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Inflammatory Cytokine ◽  
Cytokine Signaling ◽  
Over Expression ◽  
Autonomous Regulation ◽  
Age Related ◽  
Evolutionarily Conserved ◽  
Age Dependent ◽  
Import Receptor

AbstractAge is a major risk factor for cardiovascular diseases. Currently, the non-autonomous regulation of age-related cardiac dysfunction is poorly understood. In the present study, we discover that age-dependent induction of cytokine unpaired 3 (Upd3) in Drosophila oenocytes (hepatocyte-like cells), due to a dampened peroxisomal import function, is the primary non-autonomous mechanism for elevated arrhythmicity in old hearts. We show that Upd3 is significantly up-regulated (52-fold) in aged oenocytes. Oenocyte-specific knockdown of Upd3 is sufficient to block aging-induced cardiac arrhythmia. We further show that the age-dependent induction of Upd3 is triggered by impaired peroxisomal import and elevated JNK signaling in aged oenocytes. Intriguingly, oenocyte-specific over-expression of Pex5, the key peroxisomal import receptor, restores peroxisomal import, blocks age-related Upd3 induction, and alleviates aging- and paraquat-induced cardiac arrhythmicity. Thus, our studies identify an important role of the evolutionarily conserved pro-inflammatory cytokine signaling and hepatocyte-specific peroxisomal import in mediating non-autonomous regulation of cardiac aging.

scholarly journals Immunosenescence in Choroidal Neovascularization (CNV)—Transcriptional Profiling of Naïve and CNV-Associated Retinal Myeloid Cells during Aging

2021 ◽  
Vol 22 (24) ◽  
pp. 13318
Author(s):  
Anja Schlecht ◽  
Adrian Thien ◽  
Julian Wolf ◽  
Gabriele Prinz ◽  
Hansjürgen Agostini ◽  
...  
Keyword(s):  
Choroidal Neovascularization ◽  
Transcriptional Profiling ◽  
Myeloid Cells ◽  
Age Related Macular Degeneration ◽  
Physiological Aging ◽  
Future Studies ◽  
Signature Genes ◽  
Age Related ◽  
Age Dependent

Immunosenescence is considered a possible factor in the development of age-related macular degeneration and choroidal neovascularization (CNV). However, age-related changes of myeloid cells (MCs), such as microglia and macrophages, in the healthy retina or during CNV formation are ill-defined. In this study, Cx3cr1-positive MCs were isolated by fluorescence-activated cell sorting from six-week (young) and two-year-old (old) Cx3cr1GFP/+ mice, both during physiological aging and laser-induced CNV development. High-throughput RNA-sequencing was performed to define the age-dependent transcriptional differences in MCs during physiological aging and CNV development, complemented by immunohistochemical characterization and the quantification of MCs, as well as CNV size measurements. These analyses revealed that myeloid cells change their transcriptional profile during both aging and CNV development. In the steady state, senescent MCs demonstrated an upregulation of factors contributing to cell proliferation and chemotaxis, such as Cxcl13 and Cxcl14, as well as the downregulation of microglial signature genes. During CNV formation, aged myeloid cells revealed a significant upregulation of angiogenic factors such as Arg1 and Lrg1 concomitant with significantly enlarged CNV and an increased accumulation of MCs in aged mice in comparison to young mice. Future studies need to clarify whether this observation is an epiphenomenon or a causal relationship to determine the role of immunosenescence in CNV formation.

scholarly journals Sirtuins, Bioageing, and Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
D. McGuinness ◽  
D. H. McGuinness ◽  
J. A. McCaul ◽  
P. G. Shiels
Keyword(s):  
Cell Cycle ◽  
Genomic Stability ◽  
Degenerative Diseases ◽  
Critical Junctures ◽  
Age Related ◽  
Wide Range ◽  
Telomere Function ◽  
And Function ◽  
High Degree

The Sirtuins are a family of orthologues of yeast Sir2 found in a wide range of organisms from bacteria to man. They display a high degree of conservation between species, in both sequence and function, indicative of their key biochemical roles. Sirtuins are heavily implicated in cell cycle, cell division, transcription regulation, and metabolism, which places the various family members at critical junctures in cellular metabolism. Typically, Sirtuins have been implicated in the preservation of genomic stability and in the prolongation of lifespan though many of their target interactions remain unknown. Sirtuins play key roles in tumourigenesis, as some have tumour-suppressor functions and others influence tumours through their control of the metabolic state of the cell. Their links to ageing have also highlighted involvement in various age-related and degenerative diseases. Here, we discuss the current understanding of the role of Sirtuins in age-related diseases while taking a closer look at their roles and functions in maintaining genomic stability and their influence on telomerase and telomere function.

Age-dependent changes in GI physiology and microbiota: time to reconsider?

Gut ◽  
2018 ◽  
Vol 67 (12) ◽  
pp. 2213-2222 ◽  
Author(s):  
Ran An ◽  
Ellen Wilms ◽  
Ad A M Masclee ◽  
Hauke Smidt ◽  
Erwin G Zoetendal ◽  
...  
Keyword(s):  
Adaptive Capacity ◽  
Intestinal Microbiota ◽  
Physiological Function ◽  
The Elderly ◽  
Population Ageing ◽  
Ageing Population ◽  
Targeted Interventions ◽  
Age Related ◽  
Age Dependent ◽  
And Function

Our life expectancy is increasing, leading to a rise in the ageing population. Ageing is associated with a decline in physiological function and adaptive capacity. Altered GI physiology can affect the amount and types of nutrients digested and absorbed as well as impact the intestinal microbiota. The intestinal microbiota is considered a key player in our health, and a variety of studies have reported that microbiota composition is changing during ageing. Since ageing is associated with a decline in GI function and adaptive capacity, it is crucial to obtain insights into this decline and how this is related to the intestinal microbiota in the elderly. Hence, in this review we focus on age-related changes in GI physiology and function, changes of the intestinal microbiota with ageing and frailty, how these are associated and how intestinal microbiota-targeted interventions may counteract these changes.

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