bims-agimec 2024-11-17 papers

Issue of 2024–11–17
seven papers selected by
Metin Sökmen, Ankara Üniversitesi

Front Genet. 2024 ;15 1509961

Editorial: Genetic and molecular mechanisms of healthy aging and age-related diseases.

Yunpeng Xu, Jiang-An Yin, Zhiyong Shao.

Keywords: age-related diseases; aging; genetic; lifespan; molecular

DOI: https://doi.org/10.3389/fgene.2024.1509961

Int J Mol Sci. 2024 Oct 31. pii: 11720. [Epub ahead of print]25(21):

From Plaques to Pathways in Alzheimer's Disease: The Mitochondrial-Neurovascular-Metabolic Hypothesis.

Sarah Kazemeini, Ahmed Nadeem-Tariq, Ryan Shih, John Rafanan, Nabih Ghani, Thomas A Vida.

Alzheimer's disease (AD) presents a public health challenge due to its progressive neurodegeneration, cognitive decline, and memory loss. The amyloid cascade hypothesis, which postulates that the accumulation of amyloid-beta (Aβ) peptides initiates a cascade leading to AD, has dominated research and therapeutic strategies. The failure of recent Aβ-targeted therapies to yield conclusive benefits necessitates further exploration of AD pathology. This review proposes the Mitochondrial-Neurovascular-Metabolic (MNM) hypothesis, which integrates mitochondrial dysfunction, impaired neurovascular regulation, and systemic metabolic disturbances as interrelated contributors to AD pathogenesis. Mitochondrial dysfunction, a hallmark of AD, leads to oxidative stress and bioenergetic failure. Concurrently, the breakdown of the blood-brain barrier (BBB) and impaired cerebral blood flow, which characterize neurovascular dysregulation, accelerate neurodegeneration. Metabolic disturbances such as glucose hypometabolism and insulin resistance further impair neuronal function and survival. This hypothesis highlights the interconnectedness of these pathways and suggests that therapeutic strategies targeting mitochondrial health, neurovascular integrity, and metabolic regulation may offer more effective interventions. The MNM hypothesis addresses these multifaceted aspects of AD, providing a comprehensive framework for understanding disease progression and developing novel therapeutic approaches. This approach paves the way for developing innovative therapeutic strategies that could significantly improve outcomes for millions affected worldwide.

Keywords: Alzheimer’s disease; amyloid-beta peptide; blood–brain barrier; metabolic disturbances; mitochondrial dysfunction; neurodegeneration; neurovascular regulation; oxidative stress

DOI: https://doi.org/10.3390/ijms252111720

Ageing Res Rev. 2024 Nov 13. pii: S1568-1637(24)00400-8. [Epub ahead of print] 102582

Semaglutide as a Possible Therapy for Healthy Aging: Targeting the Hallmarks of Aging.

Gabriela Ueta Ortiz, Ellen Cristini de Freitas.

With an aging population, the investigation of therapies that promote healthy aging becomes increasingly urgent. Here we discuss how Semaglutide can be a potential therapy to contribute to this goal by targeting key hallmarks of aging, such as inflammation, oxidative stress and stem cell exhaustion.

Keywords: healthy aging; inflammation; oxidative stress; semaglutide; stem cell exhaustion

DOI: https://doi.org/10.1016/j.arr.2024.102582

Cells. 2024 Oct 29. pii: 1788. [Epub ahead of print]13(21):

Molecular and Cellular Effects of Microplastics and Nanoplastics: Focus on Inflammation and Senescence.

Faiza Mahmud, Drishty B Sarker, Jonathan A Jocelyn, Qing-Xiang Amy Sang.

Microplastics and nanoplastics (MNPs) are ubiquitous environmental contaminants. Their prevalence, persistence, and increasing industrial production have led to questions about their long-term impact on human and animal health. This narrative review describes the effects of MNPs on oxidative stress, inflammation, and aging. Exposure to MNPs leads to increased production of reactive oxygen species (ROS) across multiple experimental models, including cell lines, organoids, and animal systems. ROS can cause damage to cellular macromolecules such as DNA, proteins, and lipids. Direct interaction between MNPs and immune cells or an indirect result of oxidative stress-mediated cellular damage may lead to increased production of pro-inflammatory cytokines throughout different MNP-exposure conditions. This inflammatory response is a common feature in the pathogenesis of neurodegenerative, cardiovascular, and other age-related diseases. MNPs also act as cell senescence inducers by promoting mitochondrial dysfunction, impairing autophagy, and activating DNA damage responses, exacerbating cellular aging altogether. Increased senescence of reproductive cells and transfer of MNPs/induced damages from parents to offspring in animals further corroborates the transgenerational health risks of the tiny particles. This review aims to provoke a deeper investigation into the notorious effects these pervasive particles may have on human well-being and longevity.

Keywords: DNA damage; cellular aging; cytotoxicity; environmental pollutants; human health; inflammation; microplastics; nanoplastics; reactive oxygen species; senescence

DOI: https://doi.org/10.3390/cells13211788

Neuron. 2024 Nov 06. pii: S0896-6273(24)00767-0. [Epub ahead of print]

White matter aging and its impact on brain function.

Janos Groh, Mikael Simons.

Aging has a detrimental impact on white matter, resulting in reduced volume, compromised structural integrity of myelinated axons, and an increase in white matter hyperintensities. These changes are closely linked to cognitive decline and neurological disabilities. The deterioration of myelin and its diminished ability to regenerate as we age further contribute to the progression of neurodegenerative disorders. Understanding these changes is crucial for devising effective disease prevention strategies. Here, we will discuss the structural alterations in white matter that occur with aging and examine the cellular and molecular mechanisms driving these aging-related transformations. We highlight how the progressive disruption of white matter may initiate a self-perpetuating cycle of inflammation and neural damage.

Keywords: aging; myelin; neuroinflammation; white matter

DOI: https://doi.org/10.1016/j.neuron.2024.10.019

Geroscience. 2024 Nov 11.

Stay social, stay young: a bioanthropological outlook on the processes linking sociality and ageing.

Vincenzo Iannuzzi, Nicolas Narboux-Nême, Andrea Lehoczki, Giovanni Levi, Cristina Giuliani.

In modern human societies, social interactions and pro-social behaviours are associated with better individual and collective health, reduced mortality, and increased longevity. Conversely, social isolation is a predictor of shorter lifespan. The biological processes through which sociality affects the ageing process, as well as healthspan and lifespan, are still poorly understood. Unveiling the physiological, neurological, genomic, epigenomic, and evolutionary mechanisms underlying the association between sociality and longevity may open new perspectives to understand how lifespan is determined in a broader socio/evolutionary outlook. Here we summarize evidence showing how social dynamics can shape the evolution of life history traits through physiological and genetic processes directly or indirectly related to ageing and lifespan. We start by reviewing theories of ageing that incorporate social interactions into their model. Then, we address the link between sociality and lifespan from two separate points of view: (i) considering evidences from comparative evolutionary biology and bioanthropology that demonstrates how sociality contributes to natural variation in lifespan over the course of human evolution and among different human groups in both pre-industrial and post-industrial society, and (ii) discussing the main physiological, neurological, genetic, and epigenetic molecular processes at the interface between sociality and ageing. We highlight that the exposure to chronic social stressors deregulates neurophysiological and immunological pathways and promotes accelerated ageing and thereby reducing lifespan. In conclusion, we describe how sociality and social dynamics are intimately embedded in human biology, influencing healthy ageing and lifespan, and we highlight the need to foster interdisciplinary approaches including social sciences, biological anthropology, human ecology, physiology, and genetics.

Keywords: Ageing; Human evolution; Lifespan; Physiology; Sociality; Stress

DOI: https://doi.org/10.1007/s11357-024-01416-5

FEBS J. 2024 Nov 14.

Mitochondria: great balls of fire.

Howard T Jacobs, Pierre Rustin, Paule Bénit, Dan Davidi, Mügen Terzioglu.

Recent experimental studies indicate that mitochondria in mammalian cells are maintained at temperatures of at least 50 °C. While acknowledging the limitations of current experimental methods and their interpretation, we here consider the ramifications of this finding for cellular functions and for evolution. We consider whether mitochondria as heat-producing organelles had a role in the origin of eukaryotes and in the emergence of homeotherms. The homeostatic responses of mitochondrial temperature to externally applied heat imply the existence of a molecular heat-sensing system in mitochondria. While current findings indicate high temperatures for the innermost compartments of mitochondria, those of the mitochondrial surface and of the immediately surrounding cytosol remain to be determined. We ask whether some aspects of mitochondrial dynamics and motility could reflect changes in the supply and demand for mitochondrial heat, and whether mitochondrial heat production could be a factor in diseases and immunity.

Keywords: cold‐shock; eukaryote origins; heat‐shock; homeothermy; immunity; mitochondria; mitochondrial disease; mitochondrial dynamics; temperature gradients; thermogenesis

DOI: https://doi.org/10.1111/febs.17316