bims-agimec 2025-02-16 papers

bims-agimec

Biomed News

on Aging mechanisms

Issue of 2025–02–16
seven papers selected by
Metin Sökmen, Ankara Üniversitesi

From bench to bedside: translational insights into aging research.
Aging, cancer, and autophagy: connections and therapeutic perspectives.
Mitochondrial Alterations, Oxidative Stress, and Therapeutic Implications in Alzheimer's Disease: A Narrative Review.
Metabolaging: a new geroscience perspective linking aging pathologies and metabolic dysfunction.
The link between sarcopenic obesity and Alzheimer's disease: a brain-derived neurotrophic factor point of view.
Advancements in autophagy perturbations in Alzheimer's disease: Molecular aspects and therapeutics.
Vectors in CRISPR Gene Editing for Neurological Disorders: Challenges and Opportunities.

Front Aging. 2025 ;6 1492099

From bench to bedside: translational insights into aging research.

Kanti Bhooshan Pandey.

  Aging research has rapidly advanced from fundamental discoveries at the molecular and cellular levels to promising clinical applications. This review discusses the critical translational insights that bridge the gap between bench research and bedside applications, highlighting key discoveries in the mechanisms of aging, biomarkers, and therapeutic interventions. It underscores the importance of interdisciplinary approaches and collaboration among scientists, clinicians, and policymakers to address the complexities of aging and improve health span.

Keywords:  aging; biomarkers; genomic instability; interventions; longevity; oxidative stress

DOI:  https://doi.org/10.3389/fragi.2025.1492099
Front Mol Biosci. 2024 ;11 1516789

Aging, cancer, and autophagy: connections and therapeutic perspectives.

Begoña Zapatería, Esperanza Arias.

  Aging and cancer are intricately linked through shared molecular processes that influence both the onset of malignancy and the progression of age-related decline. As organisms age, cellular stress, genomic instability, and an accumulation of senescent cells create a pro-inflammatory environment conducive to cancer development. Autophagy, a cellular process responsible for degrading and recycling damaged components, plays a pivotal role in this relationship. While autophagy acts as a tumor-suppressive mechanism by preventing the accumulation of damaged organelles and proteins, cancer cells often exploit it to survive under conditions of metabolic stress and treatment resistance. The interplay between aging, cancer, and autophagy reveals key insights into tumorigenesis, cellular senescence, and proteostasis dysfunction. This review explores the molecular connections between these processes, emphasizing the potential for autophagy-targeted therapies as strategies that could be further explored in both aging and cancer treatment. Understanding the dual roles of autophagy in suppressing and promoting cancer offers promising avenues for therapeutic interventions aimed at improving outcomes for elderly cancer patients while addressing age-related deterioration.

Keywords:  aging; autopaghy; cancer; proteostasis; therapeutics

DOI:  https://doi.org/10.3389/fmolb.2024.1516789
Cells. 2025 Feb 06. pii: 229. [Epub ahead of print]14(3):

Mitochondrial Alterations, Oxidative Stress, and Therapeutic Implications in Alzheimer's Disease: A Narrative Review.

Erica Spina, Riccardo Rocco Ferrari, Elisa Pellegrini, Mauro Colombo, Tino Emanuele Poloni, Antonio Guaita, Annalisa Davin.

  The relationship between aging, mitochondrial dysfunction, neurodegeneration, and the onset of Alzheimer's disease (AD) is a complex area of study. Aging is the primary risk factor for AD, and it is associated with a decline in mitochondrial function. This mitochondrial dysfunction is believed to contribute to the neurodegenerative processes observed in AD. Neurodegeneration in AD is characterized by the progressive loss of synapses and neurons, particularly in regions of the brain involved in memory and cognition. It is hypothesized that mitochondrial dysfunction plays a pivotal role by disrupting cellular energy metabolism and increasing the production of reactive oxygen species (ROS), which can damage cellular components and exacerbate neuronal loss. Despite extensive research, the precise molecular pathways linking mitochondrial dysfunction to AD pathology are not fully understood. Various hypotheses have been proposed, including the mitochondrial cascade hypothesis, which suggests that mitochondrial dysfunction is an early event in AD pathogenesis that triggers a cascade of cellular events leading to neurodegeneration. With this narrative review, we aim to summarize some specific issues in the literature on mitochondria and their involvement in AD onset, with a focus on the development of therapeutical strategies targeting the mitochondria environment and their potential application for the treatment of AD itself.

Keywords:  Alzheimer’s disease; aging; mitochondria; mitochondrial dysfunction

DOI:  https://doi.org/10.3390/cells14030229
Metabolism. 2025 Feb 11. pii: S0026-0495(25)00027-7. [Epub ahead of print]166 156158

Metabolaging: a new geroscience perspective linking aging pathologies and metabolic dysfunction.

Fadi Khalaf, Dalia Barayan, Sean Saldanha, Marc G Jeschke.

  With age, our metabolic systems undergo significant alterations, which can lead to a cascade of adverse effects that are implicated in both metabolic disorders, such as diabetes, and in the body's ability to respond to acute stress and trauma. To elucidate the metabolic imbalances arising from aging, we introduce the concept of "metabolaging." This framework encompasses the broad spectrum of metabolic disruptions associated with the hallmarks of aging, including the functional decline of key metabolically active organs, like the adipose tissue. By examining how these organs interact with essential nutrient-sensing pathways, "metabolaging" provides a more comprehensive view of the systemic metabolic imbalances that occur with age. This concept extends to understanding how age-related metabolic disturbances can influence the response to acute stressors, like burn injuries, highlighting the interplay between metabolic dysfunction and the ability to handle severe physiological challenges. Finally, we propose potential interventions that hold promise in mitigating the effects of metabolaging and its downstream consequences.

Keywords:  Adipose tissue; Aging; Burn injury; Hypermetabolism; Inflammaging; Metabolaging; Metabolism

DOI:  https://doi.org/10.1016/j.metabol.2025.156158
J Physiol. 2025 Feb 12.

The link between sarcopenic obesity and Alzheimer's disease: a brain-derived neurotrophic factor point of view.

Emily N Copeland, Paul J LeBlanc, Paula Duarte-Guterman, Val A Fajardo, Rebecca E K MacPherson.

  Age-related diseases are becoming more prominent as the lifespan of the global population rises. Many of these diseases coincide with each other and can even influence the onset of additional comorbidities. Sarcopenic obesity is described as age-related loss of muscle mass that concurs with excessive weight gain and tends to increase the risk of comorbidity development, including Alzheimer's disease (AD). Though the exact link between sarcopenic obesity and AD is not known, this review explores the possibility that reduced levels of brain-derived neurotrophic factor (BDNF) throughout the body may serve as the underlying commonality. In AD, reductions in BDNF signalling through its receptor promote the activation of glycogen synthase kinase 3 beta (GSK3β), which subsequently increases the production of amyloid beta (Aβ) peptides and neurofibrillary tangles (NFTs). In the skeletal muscle, lower BDNF concentrations are linked to impaired muscle fibre repair and regeneration, increasing the likelihood of sarcopenia. Furthermore, the absence of BDNF impairs mitochondrial function, leading to insulin resistance and increased adiposity. BDNF concentration has a negative relationship with obesogenic markers in adipose tissue, and as such, lower concentrations of BDNF lead to weight gain. Collectively, current literature suggests that BDNF attenuates AD pathology while improving skeletal muscle mitochondrial function, whole-body insulin resistance and facilitating adipocyte browning. Therefore, BDNF may be a viable target for multiple age-related diseases, but more research is required to substantiate this claim, with a particular focus on examining any potential influence of biological sex, as women are at a higher risk for both AD and sarcopenic obesity.

Keywords:  adipose tissue; ageing; brain; crosstalk; skeletal muscle

DOI:  https://doi.org/10.1113/JP288032
Brain Res. 2025 Feb 06. pii: S0006-8993(25)00052-6. [Epub ahead of print]1851 149494

Advancements in autophagy perturbations in Alzheimer's disease: Molecular aspects and therapeutics.

Rishika Dhapola, Sneha Kumari, Prajjwal Sharma, Balachandar Vellingiri, Dibbanti HariKrishnaReddy.

  Emerging evidences suggest that autophagy, a key cellular process responsible for degrading and recycling damaged organelles and proteins, plays a crucial role in maintaining neuronal health. Dysfunctional autophagy has been linked to the pathogenesis of Alzheimer's disease (AD), contributing to the accumulation of misfolded proteins and cellular debris. Molecular mechanisms underlying autophagy dysfunction in AD involve amyloid-beta (Aβ) and tau accumulation, neuroinflammation, mitochondrial dysfunction, oxidative stress and endoplasmic reticulum stress. Disrupted signaling pathways such as TRIB3, Nmnat and BAG3 that regulate key processes like autophagosome initiation, lysosome function, and protein homeostasis also play a crucial role in the pathogenesis. Restoration of autophagy by modulating these molecular and signaling pathways may be an effective therapeutic strategy for AD. Studies have found few drugs targeting autophagy dysregulation in AD. These drugs include metformin that has been found to modulate the expression of TRIB3 for autophagy regulation. Another drug, resveratrol has been reported to augment the activity of Nmnat thus, increases autophagy flux. BACE1 and mTOR inhibitors like arctigenin, nilvadipine and dapagliflozin were also found to restore autophagy. This study elaborates recent advances in signaling and molecular pathways and discusses current and emerging therapeutic interventions targeting autophagy dysfunction in AD.

Keywords:  Alzheimer’s disease; Autophagy; Molecular pathways; Signaling pathways; Therapeutics

DOI:  https://doi.org/10.1016/j.brainres.2025.149494
Adv Biol (Weinh). 2025 Feb 14. e2400374

Vectors in CRISPR Gene Editing for Neurological Disorders: Challenges and Opportunities.

Kexin Xiong, Xiaxia Wang, Caicai Feng, Kaixiang Zhang, Di Chen, Sen Yang.

  Diseases of the nervous system are recognized as the second leading cause of death worldwide. The global prevalence of neurological diseases, such as Huntington's disease, Alzheimer's disease, and Parkinson's disease has seen a significant rise due to the increasing proportion of the aging population. The discovery of the clustered regularly interspaced short palindromic repeats (CRISPR) genome editing technique has paved way for universal neurological diseases treatment. However, finding a safe and effective method to deliver CRISPR gene-editing tools remains a main challenge for genome editing therapies in vivo. Adeno-associated virus (AAV) is currently one of the most commonly used vector systems, but some issues remain unresolved, including capsid immunogenicity, off-target mutations, and potential genotoxicity. To address these concerns, researchers are actively encouraging the development of new delivery systems, like virus-like particles and nanoparticles. These novel systems have the potential to enhance targeting efficiency, thereby offering possible solutions to the current challenges. This article reviews CRISPR delivery vectors for neurological disorders treatment and explores potential solutions to overcome limitations in vector systems. Additionally, the delivery strategies of CRISPR systems are highlighted as valuable tools for studying neurological diseases, and the challenges and opportunities that these vectors present.

Keywords:  CRISPR; adeno‐associated virus; nanoparticles; neurological disease; vectors; virus‐like particles

DOI:  https://doi.org/10.1002/adbi.202400374