bims-agimec 2024-10-13 papers

bims-agimec

Biomed News

on Aging mechanisms

Issue of 2024‒10‒13
seven papers selected by
Metin Sökmen, Ankara Üniversitesi

Synaptic Mitochondria: a crucial factor in the aged hippocampus.
Neuroprotective effects of magnesium: implications for neuroinflammation and cognitive decline.
Mechanisms of erectile dysfunction induced by aging: A comprehensive review.
Obesity-induced neuronal senescence: Unraveling the pathophysiological links.
Mitochondrial Extracellular Vesicles (mitoEVs): Emerging mediators of cell-to-cell communication in health, aging and age-related diseases.
Nicotinamide Adenine Dinucleotide (NAD)-Dependent Protein Deacetylase, Sirtuin, as a Biomarker of Healthy Life Expectancy: A Mini-Review.
Cellular senescence by loss of Men1 in osteoblasts is critical for age-related osteoporosis.

Ageing Res Rev. 2024 Oct 04. pii: S1568-1637(24)00342-8. [Epub ahead of print] 102524

Synaptic Mitochondria: a crucial factor in the aged hippocampus.

Karina A Cicali, Cheril Tapia-Rojas.

  Aging is a multifaceted biological process characterized by progressive molecular and cellular damage accumulation. The brain hippocampus undergoes functional deterioration with age, caused by cellular deficits, decreased synaptic communication, and neuronal death, ultimately leading to memory impairment. One of the factors contributing to this dysfunction is the loss of mitochondrial function. In neurons, mitochondria are categorized into synaptic and non-synaptic pools based on their location. Synaptic mitochondria, situated at the synapses, play a crucial role in maintaining neuronal function and synaptic plasticity, whereas non-synaptic mitochondria are distributed throughout other neuronal compartments, supporting overall cellular metabolism and energy supply. The proper function of synaptic mitochondria is essential for synaptic transmission as they provide the energy required and regulate calcium homeostasis at the communication sites between neurons. Maintaining the structure and functionality of synaptic mitochondria involves intricate processes, including mitochondrial dynamics such as fission, fusion, transport, and quality control mechanisms. These processes ensure that mitochondria remain functional, replace damaged organelles, and sustain cellular homeostasis at synapses. Notably, deficiencies in these mechanisms have been increasingly associated with aging and the onset of age-related neurodegenerative diseases. Synaptic mitochondria from the hippocampus are particularly vulnerable to age-related changes, including alterations in morphology and a decline in functionality, which significantly contribute to decreased synaptic activity during aging. This review comprehensively explores the critical roles that mitochondrial dynamics and quality control mechanisms play in preserving synaptic activity and neuronal function. It emphasizes the emerging evidence linking the deterioration of synaptic mitochondria to the aging process and the development of neurodegenerative diseases, highlighting the importance of these organelles from hippocampal neurons as potential therapeutic targets for mitigating cognitive decline and synaptic degeneration associated with aging. The novelty of this review lies in its focus on the unique vulnerability of hippocampal synaptic mitochondria to aging, underscoring their importance in maintaining brain function across the lifespan.

Keywords:  Aging; Cognitive Decline; Mitochondria; Mitochondrial Dysfunction; Non-synaptic; Synaptic

DOI:  https://doi.org/10.1016/j.arr.2024.102524
Front Endocrinol (Lausanne). 2024 ;15 1406455

Neuroprotective effects of magnesium: implications for neuroinflammation and cognitive decline.

Veer Patel, Nuraly S Akimbekov, William B Grant, Carolyn Dean, Xiaoqian Fang, Mohammed S Razzaque.

  Neurodegenerative diseases, which are characterized by progressive neuronal loss and cognitive decline, are a significant concern for the aging population. Neuroinflammation, a shared characteristic of these diseases, is implicated in their pathogenesis. This article briefly summarizes the role of magnesium, an essential mineral involved in numerous enzymatic reactions and critical for neuronal bioactivity, in the context of neuroinflammation and cognitive decline. The potential neuroprotective effects of magnesium, including the mechanisms of neuroprotection by magnesium through maintaining neuronal ion homeostasis, reducing inflammation, and preventing excitotoxicity, are also described. Additionally, we discuss the impact of inadequate magnesium on neuroinflammation and its potential as a therapeutic agent for attenuating cognitive decline to improve neurodegenerative conditions.

Keywords:  cognitive decline; magnesium; neurodegenerative disease; neuroinflammation; neuroprotection

DOI:  https://doi.org/10.3389/fendo.2024.1406455
Andrology. 2024 Oct 09.

Mechanisms of erectile dysfunction induced by aging: A comprehensive review.

Baojun Zhuang, Chenglin Zhuang, Yongze Jiang, Jingyi Zhang, Yandong Zhang, Peihai Zhang, Xujun Yu, Suyun Xu.

  BACKGROUND: With the increasing trend ofpopulation aging, erectile dysfunction (ED) among elderly men has emerged as apressing health concern. Despite extensive research on the relationship betweenED and aging, ongoing discoveries and evidence continue to arise.OBJECTIVE: Through this comprehensiveanalysis, we aim to provide a more nuanced theoretical framework for thedevelopment of preventive and therapeutic strategies for senile ED, ultimatelyenhancing the quality of life for elderly men.
METHODS: This review delves deeper into thecore mechanisms underlying ED in the context of aging and offers acomprehensive overview of published meta-analyses and systematic reviewspertinent to these conditions.
RESULTS AND CONCLUSION: Our findings revealthat local structural damage to the penis, vascular dysfunction, neuronalinjury, hormonal alterations, other physiological changes, and psychologicalbarriers all play pivotal roles in the pathogenesis of aging-related ED.Furthermore, more than 20 diseases closely associated with aging have beenimplicated in the occurrence of ED, further compounding the complexity of thisissue.

Keywords:  aging; erectile dysfunction; review

DOI:  https://doi.org/10.1111/andr.13778
Ageing Res Rev. 2024 Oct 03. pii: S1568-1637(24)00351-9. [Epub ahead of print]101 102533

Obesity-induced neuronal senescence: Unraveling the pathophysiological links.

Puja Ghosh, Rosaria Anna Fontanella, Lucia Scisciola, Fatemeh Taktaz, Ada Pesapane, Manuela Giovanna Basilicata, Giovanni Tortorella, Giulia Mattacchione, Annalisa Capuano, Maria Teresa Vietri, Francesco Selvaggi, Giuseppe Paolisso, Michelangela Barbieri.

  Obesity is one of the most prevalent and increasing metabolic disorders and is considered one of the twelve risk factors for dementia. Numerous studies have demonstrated that obesity induces pathophysiological changes leading to cognitive decline; however, the underlying molecular mechanisms are yet to be fully elucidated. Various biochemical processes, including chronic inflammation, oxidative stress, insulin resistance, dysregulation of lipid metabolism, disruption of the blood-brain barrier, and the release of adipokines have been reported to contribute to the accumulation of senescent neurons during obesity. These senescent cells dysregulate neuronal health and function by exhibiting a senescence-associated secretory phenotype, inducing neuronal inflammation, deregulating cellular homeostasis, causing mitochondrial dysfunction, and promoting microglial infiltration. These factors act as major risks for the occurrence of neurodegenerative diseases and cognitive decline. This review aims to focus on how obesity upregulates neuronal senescence and explores both pharmacological and non-pharmacological interventions for preventing cognitive impairments, thus offering new insights into potential therapeutic strategies.

Keywords:  Adipokines; Cognitive decline; Neuronal senescence; Obesity; SASP

DOI:  https://doi.org/10.1016/j.arr.2024.102533
Ageing Res Rev. 2024 Oct 05. pii: S1568-1637(24)00340-4. [Epub ahead of print]101 102522

Mitochondrial Extracellular Vesicles (mitoEVs): Emerging mediators of cell-to-cell communication in health, aging and age-related diseases.

Roberto Iorio, Sabrina Petricca, Giovanna Di Emidio, Stefano Falone, Carla Tatone.

  Mitochondria are metabolic and signalling hubs that integrate a plethora of interconnected processes to maintain cell homeostasis. They are also dormant mediators of inflammation and cell death, and with aging damages affecting mitochondria gradually accumulate, resulting in the manifestation of age-associated disorders. In addition to coordinate multiple intracellular functions, mitochondria mediate intercellular and inter-organ cross talk in different physiological and stress conditions. To fulfil this task, mitochondrial signalling has evolved distinct and complex conventional and unconventional routes of horizontal/vertical mitochondrial transfer. In this regard, great interest has been focused on the ability of extracellular vesicles (EVs), such as exosomes and microvesicles, to carry selected mitochondrial cargoes to target cells, in response to internal and external cues. Over the past years, the field of mitochondrial EVs (mitoEVs) has grown exponentially, revealing unexpected heterogeneity of these structures associated with an ever-expanding mitochondrial function, though the full extent of the underlying mechanisms is far from being elucidated. Therefore, emerging subsets of EVs encompass exophers, migrasomes, mitophers, mitovesicles, and mitolysosomes that can act locally or over long-distances to restore mitochondrial homeostasis and cell functionality, or to amplify disease. This review provides a comprehensive overview of our current understanding of the biology and trafficking of MitoEVs in different physiological and pathological conditions. Additionally, a specific focus on the role of mitoEVs in aging and the onset and progression of different age-related diseases is discussed.

Keywords:  Age-related diseases; Bioenergetic remodelling; Cancer; Intercellular communication; Mitochondria-specific ectocytosis; Mitochondrial derived vesicles (MDVs); Mitochondrial extracellular vesicles (mitoEVs); Mitochondrial quality control (MQC)

DOI:  https://doi.org/10.1016/j.arr.2024.102522
Curr Aging Sci. 2024 Oct 04.

Nicotinamide Adenine Dinucleotide (NAD)-Dependent Protein Deacetylase, Sirtuin, as a Biomarker of Healthy Life Expectancy: A Mini-Review.

Yodo Sugishita, Yuki Suzuki-Takahashi, Kazuo Yudoh.

  Although a variety of disease-specific biomarkers have been identified for common lifestyle- or aging-related diseases, there are currently no indices available to measure general health or the existence of pre-symptomatic conditions in various types of tissue and organ damage. A rising body of research suggests that sirtuins may have the potential to be used as an index to assess overall health status and the existence of pre-symptomatic illness states. Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD)-dependent deacetylases expressed in a variety of human somatic cells both in health and disease conditions. The activity and expression of SIRTs affect important metabolic pathways, such as cell survival, senescence, proliferation, energy production, stress tolerance, DNA repair, and apoptosis, thereby closely linked to aging and longevity. Given the broad significance of SIRTs in physiological function maintenance, their activity in somatic cells may reflect the early cross-sectional status of tissue damage caused by aging or systemic inflammatory responses that are too early to be detected by disease-specific biomarkers. In this mini-review, we discuss the utility of SIRTs as a surrogate clinical biomarker for health status to evaluate and monitor health life expectancy and the presence of pre-symptomatic illness states.

Keywords:  Aging; healthy life expectancy biomarkers; sirtuin.; surrogate markers

DOI:  https://doi.org/10.2174/0118746098319674240827104612
Aging Cell. 2024 Oct;23(10): e14254

Cellular senescence by loss of Men1 in osteoblasts is critical for age-related osteoporosis.

Yuichiro Ukon, Takashi Kaito, Hiromasa Hirai, Takayuki Kitahara, Masayuki Bun, Joe Kodama, Daisuke Tateiwa, Shinichi Nakagawa, Masato Ikuta, Takuya Furuichi, Yuya Kanie, Takahito Fujimori, Shota Takenaka, Tadashi Yamamuro, Satoru Otsuru, Seiji Okada, Masakatsu Yamashita, Takeshi Imamura.

  Recent evidence suggests an association between age-related osteoporosis and cellular senescence in the bone; however, the specific bone cells that play a critical role in age-related osteoporosis and the mechanism remain unknown. Results revealed that age-related osteoporosis is characterized by the loss of osteoblast Men1. Osteoblast-specific inducible knockout of Men1 caused structural changes in the mice bones, matching the phenotypes in patients with age-related osteoporosis. Histomorphometrically, Men1-knockout mice femurs decreased osteoblastic activity and increased osteoclastic activity, hallmarks of age-related osteoporosis. Loss of Men1 induces cellular senescence via mTORC1 activation and AMPK suppression, rescued by metformin treatment. In bone morphogenetic protein-indued bone model, loss of Men1 leads to accumulation of senescent cells and osteoporotic bone formation, which are ameliorated by metformin. Our results indicate that cellular senescence in osteoblasts plays a critical role in age-related osteoporosis and that osteoblast-specific inducible Men1-knockout mice offer a promising model for developing therapeutics for age-related osteoporosis.

Keywords:  AMPK; Men1; cellular senescence; mTORC1; osteoporosis

DOI:  https://doi.org/10.1111/acel.14254