bims-agimec 2024-10-20 papers

Issue of 2024–10–20
seven papers selected by
Metin Sökmen, Ankara Üniversitesi

MedComm (2020). 2024 Nov;5(11): e786

Hypoxia and aging: molecular mechanisms, diseases, and therapeutic targets.

Ayesha Nisar, Sawar Khan, Wen Li, Li Hu, Priyadarshani Nadeeshika Samarawickrama, Naheemat Modupeola Gold, Meiting Zi, Sardar Azhar Mehmood, Jiarong Miao, Yonghan He.

Aging is a complex biological process characterized by the gradual decline of cellular functions, increased susceptibility to diseases, and impaired stress responses. Hypoxia, defined as reduced oxygen availability, is a critical factor that influences aging through molecular pathways involving hypoxia-inducible factors (HIFs), oxidative stress, inflammation, and epigenetic modifications. This review explores the interconnected roles of hypoxia in aging, highlighting how hypoxic conditions exacerbate cellular damage, promote senescence, and contribute to age-related pathologies, including cardiovascular diseases, neurodegenerative disorders, cancer, metabolic dysfunctions, and pulmonary conditions. By examining the molecular mechanisms linking hypoxia to aging, we identify key pathways that serve as potential therapeutic targets. Emerging interventions such as HIF modulators, antioxidants, senolytics, and lifestyle modifications hold promise in mitigating the adverse effects of hypoxia on aging tissues. However, challenges such as the heterogeneity of aging, lack of reliable biomarkers, and safety concerns regarding hypoxia-targeted therapies remain. This review emphasizes the need for personalized approaches and advanced technologies to develop effective antiaging interventions. By integrating current knowledge, this review provides a comprehensive framework that underscores the importance of targeting hypoxia-induced pathways to enhance healthy aging and reduce the burden of age-related diseases.

Keywords: age‐related disease; aging; hypoxia; mechanism; therapeutic target

DOI: https://doi.org/10.1002/mco2.786

Trends Genet. 2024 Oct 17. pii: S0168-9525(24)00214-2. [Epub ahead of print]

Unraveling aging from transcriptomics.

Yuanfang Huang, Shouxuan Zhu, Shuai Yao, Haotian Zhai, Chenyang Liu, Jing-Dong J Han.

Research into aging constitutes a pivotal endeavor aimed at elucidating the underlying biological mechanisms governing aging and age-associated diseases, as well as promoting healthy longevity. Recent advances in transcriptomic technologies, such as bulk RNA sequencing (RNA-seq), single-cell transcriptomics, and spatial transcriptomics, have revolutionized our ability to study aging at unprecedented resolution and scale. These technologies present novel opportunities for the discovery of biomarkers, elucidation of molecular pathways, and development of targeted therapeutic strategies for age-related disorders. This review surveys recent breakthroughs in different types of transcripts on aging, such as mRNA, long noncoding (lnc)RNA, tRNA, and miRNA, highlighting key findings and discussing their potential implications for future studies in this field.

Keywords: aging; bulk RNA-seq; single-cell transcriptomics; spatial transcriptomics; transcriptomics

DOI: https://doi.org/10.1016/j.tig.2024.09.006

Int J Mol Sci. 2024 Sep 30. pii: 10535. [Epub ahead of print]25(19):

Inflammaging and Brain Aging.

Maria Carolina Jurcau, Anamaria Jurcau, Alexander Cristian, Vlad Octavian Hogea, Razvan Gabriel Diaconu, Vharoon Sharma Nunkoo.

Progress made by the medical community in increasing lifespans comes with the costs of increasing the incidence and prevalence of age-related diseases, neurodegenerative ones included. Aging is associated with a series of morphological changes at the tissue and cellular levels in the brain, as well as impairments in signaling pathways and gene transcription, which lead to synaptic dysfunction and cognitive decline. Although we are not able to pinpoint the exact differences between healthy aging and neurodegeneration, research increasingly highlights the involvement of neuroinflammation and chronic systemic inflammation (inflammaging) in the development of age-associated impairments via a series of pathogenic cascades, triggered by dysfunctions of the circadian clock, gut dysbiosis, immunosenescence, or impaired cholinergic signaling. In addition, gender differences in the susceptibility and course of neurodegeneration that appear to be mediated by glial cells emphasize the need for future research in this area and an individualized therapeutic approach. Although rejuvenation research is still in its very early infancy, accumulated knowledge on the various signaling pathways involved in promoting cellular senescence opens the perspective of interfering with these pathways and preventing or delaying senescence.

Keywords: astrocytes; cellular senescence; immunosenescence; microglia; neuroinflammation; senescence-associated secretory phenotype

DOI: https://doi.org/10.3390/ijms251910535

Ageing Res Rev. 2024 Oct 10. pii: S1568-1637(24)00348-9. [Epub ahead of print]101 102530

Investigation of human aging at the single-cell level.

Yunjin Li, Qixia Wang, Yuan Xuan, Jian Zhao, Jin Li, Yuncai Tian, Geng Chen, Fei Tan.

Human aging is characterized by a gradual decline in physiological functions and an increased susceptibility to various diseases. The complex mechanisms underlying human aging are still not fully elucidated. Single-cell sequencing (SCS) technologies have revolutionized aging research by providing unprecedented resolution and detailed insights into cellular diversity and dynamics. In this review, we discuss the application of various SCS technologies in human aging research, encompassing single-cell, genomics, transcriptomics, epigenomics, and proteomics. We also discuss the combination of multiple omics layers within single cells and the integration of SCS technologies with advanced methodologies like spatial transcriptomics and mass spectrometry. These approaches have been essential in identifying aging biomarkers, elucidating signaling pathways associated with aging, discovering novel aging cell subpopulations, uncovering tissue-specific aging characteristics, and investigating aging-related diseases. Furthermore, we provide an overview of aging-related databases that offer valuable resources for enhancing our understanding of the human aging process.

Keywords: Aging-related diseases; Biomarkers; Human aging; Single-cell multi-omics; Single-cell sequencing

DOI: https://doi.org/10.1016/j.arr.2024.102530

Nutrients. 2024 Sep 27. pii: 3271. [Epub ahead of print]16(19):

Emerging Targets and Treatments for Sarcopenia: A Narrative Review.

Stefano Cacciatore, Riccardo Calvani, Ilaria Esposito, Claudia Massaro, Giordana Gava, Anna Picca, Matteo Tosato, Emanuele Marzetti, Francesco Landi.

BACKGROUND: Sarcopenia is characterized by the progressive loss of skeletal muscle mass, strength, and function, significantly impacting overall health and quality of life in older adults. This narrative review explores emerging targets and potential treatments for sarcopenia, aiming to provide a comprehensive overview of current and prospective interventions.
METHODS: The review synthesizes current literature on sarcopenia treatment, focusing on recent advancements in muscle regeneration, mitochondrial function, nutritional strategies, and the muscle-microbiome axis. Additionally, pharmacological and lifestyle interventions targeting anabolic resistance and neuromuscular junction integrity are discussed.
RESULTS: Resistance training and adequate protein intake remain the cornerstone of sarcopenia management. Emerging strategies include targeting muscle regeneration through myosatellite cell activation, signaling pathways, and chronic inflammation control. Gene editing, stem cell therapy, and microRNA modulation show promise in enhancing muscle repair. Addressing mitochondrial dysfunction through interventions aimed at improving biogenesis, ATP production, and reducing oxidative stress is also highlighted. Nutritional strategies such as leucine supplementation and anti-inflammatory nutrients, along with dietary modifications and probiotics targeting the muscle-microbiome interplay, are discussed as potential treatment options. Hydration and muscle-water balance are emphasized as critical in maintaining muscle health in older adults.
CONCLUSIONS: A combination of resistance training, nutrition, and emerging therapeutic interventions holds potential to significantly improve muscle function and overall health in the aging population. This review provides a detailed exploration of both established and novel approaches for the prevention and management of sarcopenia, highlighting the need for further research to optimize these strategies.

Keywords: hydration; inflammaging; mitochondrial dysfunction; muscle health; neuromuscular junction; physical performance; satellite cells

DOI: https://doi.org/10.3390/nu16193271

Neuron. 2024 Oct 08. pii: S0896-6273(24)00663-9. [Epub ahead of print]

Autophagy, aging, and age-related neurodegeneration.

Jennifer E Palmer, Niall Wilson, Sung Min Son, Pawel Obrocki, Lidia Wrobel, Matea Rob, Michael Takla, Viktor I Korolchuk, David C Rubinsztein.

Autophagy is a conserved mechanism that degrades damaged or superfluous cellular contents and enables nutrient recycling under starvation conditions. Many neurodegeneration-associated proteins are autophagy substrates, and autophagy upregulation ameliorates disease in many animal models of neurodegeneration by enhancing the clearance of toxic proteins, proinflammatory molecules, and dysfunctional organelles. Autophagy inhibition also induces neuronal and glial senescence, a phenomenon that occurs with increasing age in non-diseased brains as well as in response to neurodegeneration-associated stresses. However, aging and many neurodegeneration-associated proteins and mutations impair autophagy. This creates a potentially detrimental feedback loop whereby the accumulation of these disease-associated proteins impairs their autophagic clearance, facilitating their further accumulation and aggregation. Thus, understanding how autophagy interacts with aging, senescence, and neurodegenerative diseases in a temporal, cellular, and genetic context is important for the future clinical application of autophagy-modulating therapies in aging and neurodegeneration.

Keywords: Alzheimer’s disease; Huntington’s disease; Parkinson’s disease; aging; autophagy; frontotemporal dementia; motor neuron disease; neurodegeneration; senescence

DOI: https://doi.org/10.1016/j.neuron.2024.09.015

Mech Ageing Dev. 2024 Oct 11. pii: S0047-6374(24)00097-6. [Epub ahead of print]222 111997

Deciphering Osteosarcopenia through the hallmarks of aging.

Francisca Franulic, Felipe Salech, Daniel Rivas, Gustavo Duque.

Osteosarcopenia is a major driver of functional loss and a risk factor for falls, fractures, disability and mortality in older adults, urgently requiring the development of effective interventions to address it. The hallmarks of aging provide a theoretical and practical framework that allows for the structured organization of current knowledge and the planning of new development lines. This article comprehensively reviews the currently available literature on the role of the hallmarks of aging in the development of osteosarcopenia, thereby offering a panoramic view of the state of the art and knowledge gaps in this field.

Keywords: Aging; Bone; Geroscience; Muscle; Osteoporosis; Osteosarcopenia; Sarcopenia

DOI: https://doi.org/10.1016/j.mad.2024.111997