bims-agimec 2025-01-05 papers

bims-agimec

Biomed News

on Aging mechanisms

Issue of 2025–01–05
seven papers selected by
Metin Sökmen, Ankara Üniversitesi

Critical review of aging clocks and factors that may influence the pace of aging.
The Immunosenescence Clock: A New Method for Evaluating Biological Age and Predicting Mortality Risk.
Epigenetic Clocks: Beyond Biological Age, Using the Past to Predict the Present and Future.
Olfactory deficits in aging and Alzheimer's-spotlight on inhibitory interneurons.
Mitochondrial dysfunction and Alzheimer's disease: pathogenesis of mitochondrial transfer.
The role of the circadian timing system in sarcopenia in old age: a scoping review.
Connecting dots of long COVID-19 pathogenesis: a vagus nerve- hypothalamic-pituitary- adrenal-mitochondrial axis dysfunction.

Front Aging. 2024 ;5 1487260

Critical review of aging clocks and factors that may influence the pace of aging.

Mildred Min, Caitlin Egli, Ajay S Dulai, Raja K Sivamani.

   Background and objectives: Aging clocks are computational models designed to measure biological age and aging rate based on age-related markers including epigenetic, proteomic, and immunomic changes, gut and skin microbiota, among others. In this narrative review, we aim to discuss the currently available aging clocks, ranging from epigenetic aging clocks to visual skin aging clocks.
Methods: We performed a literature search on PubMed/MEDLINE databases with keywords including: "aging clock," "aging," "biological age," "chronological age," "epigenetic," "proteomic," "microbiome," "telomere," "metabolic," "inflammation," "glycomic," "lifestyle," "nutrition," "diet," "exercise," "psychosocial," and "technology."
Results: Notably, several CpG regions, plasma proteins, inflammatory and immune biomarkers, microbiome shifts, neuroimaging changes, and visual skin aging parameters demonstrated roles in aging and aging clock predictions. Further analysis on the most predictive CpGs and biomarkers is warranted. Limitations of aging clocks include technical noise which may be corrected with additional statistical techniques, and the diversity and applicability of samples utilized.
Conclusion: Aging clocks have significant therapeutic potential to better understand aging and the influence of chronic inflammation and diseases in an expanding older population.

Keywords:  PACE; aging; biological age; clock; epigenetic; microbiome; proteomic

DOI:  https://doi.org/10.3389/fragi.2024.1487260
Ageing Res Rev. 2024 Dec 31. pii: S1568-1637(24)00471-9. [Epub ahead of print] 102653

The Immunosenescence Clock: A New Method for Evaluating Biological Age and Predicting Mortality Risk.

Shuyu Li, Ke Wang, Jingni Wu, Yongliang Zhu.

  Precisely assessing an individual's immune age is critical for developing targeted aging interventions. Although traditional methods for evaluating biological age, such as the use of cellular senescence markers and physiological indicators, have been widely applied, these methods inherently struggle to capture the full complexity of biological aging. We propose the concept of an 'immunosenescence clock' that evaluates immune system changes on the basis of changes in immune cell abundance and omics data (including transcriptome and proteome data), providing a complementary indicator for understanding age-related physiological transformations. Rather than claiming to definitively measure biological age, this approach can be divided into a biological age prediction clock and a mortality prediction clock. The main function of the biological age prediction clock is to reflect the physiological state through the transcriptome data of peripheral blood mononuclear cells (PBMCs), whereas the mortality prediction clock emphasizes the ability to identify people at high risk of mortality and disease. We hereby present nearly all of the immunosenescence clocks developed to date, as well as their functional differences. Critically, we explicitly acknowledge that no single diagnostic test can exhaustively capture the intricate changes associated with biological aging. Furthermore, as these biological functions are based on the acceleration or delay of immunosenescence, we also summarize the factors that accelerate immunosenescence and the methods for delaying it. A deep understanding of the regulatory mechanisms of immunosenescence can help establish more accurate immune-age models, providing support for personalized longevity interventions and improving quality of life in old age.

Keywords:  Aging; Biological age; Chronological age; Immunosenescence clocks; Mortality risk

DOI:  https://doi.org/10.1016/j.arr.2024.102653
Aging Dis. 2024 Dec 23.

Epigenetic Clocks: Beyond Biological Age, Using the Past to Predict the Present and Future.

Runyu Liang, Qiang Tang, Jia Chen, Luwen Zhu.

Predicting health trajectories and accurately measuring aging processes across the human lifespan remain profound scientific challenges. Assessing the effectiveness and impact of interventions targeting aging is even more elusive, largely due to the intricate, multidimensional nature of aging-a process that defies simple quantification. Traditional biomarkers offer only partial perspectives, capturing limited aspects of the aging landscape. Yet, over the past decade, groundbreaking advancements have emerged. Epigenetic clocks, derived from DNA methylation patterns, have established themselves as powerful aging biomarkers, capable of estimating biological age and assessing aging rates across diverse tissues with remarkable precision. These clocks provide predictive insights into mortality and age-related disease risks, effectively distinguishing biological age from chronological age and illuminating enduring questions in gerontology. Despite significant progress in epigenetic clock development, substantial challenges remain, underscoring the need for continued investigation to fully unlock their potential in the science of aging.

DOI: https://doi.org/10.14336/AD.2024.1495
Front Neurosci. 2024 ;18 1503069

Olfactory deficits in aging and Alzheimer's-spotlight on inhibitory interneurons.

Kaoutar Elhabbari, Siran Sireci, Markus Rothermel, Daniela Brunert.

  Cognitive function in healthy aging and neurodegenerative diseases like Alzheimer's disease (AD) correlates to olfactory performance. Aging and disease progression both show marked olfactory deficits in humans and rodents. As a clear understanding of what causes olfactory deficits is still missing, research on this topic is paramount to diagnostics and early intervention therapy. A recent development of this research is focusing on GABAergic interneurons. Both aging and AD show a change in excitation/inhibition balance, indicating reduced inhibitory network functions. In the olfactory system, inhibition has an especially prominent role in processing information, as the olfactory bulb (OB), the first relay station of olfactory information in the brain, contains an unusually high number of inhibitory interneurons. This review summarizes the current knowledge on inhibitory interneurons at the level of the OB and the primary olfactory cortices to gain an overview of how these neurons might influence olfactory behavior. We also compare changes in interneuron composition in different olfactory brain areas between healthy aging and AD as the most common neurodegenerative disease. We find that pathophysiological changes in olfactory areas mirror findings from hippocampal and cortical regions that describe a marked cell loss for GABAergic interneurons in AD but not aging. Rather than differences in brain areas, differences in vulnerability were shown for different interneuron populations through all olfactory regions, with somatostatin-positive cells most strongly affected.

Keywords:  Alzheimer’s disease; aging; inhibition; interneurons; olfaction

DOI:  https://doi.org/10.3389/fnins.2024.1503069
Front Aging Neurosci. 2024 ;16 1517965

Mitochondrial dysfunction and Alzheimer's disease: pathogenesis of mitochondrial transfer.

Yun Wei, Xinlei Du, Hongling Guo, Jingjing Han, Meixia Liu.

  In recent years, mitochondrial transfer has emerged as a universal phenomenon intertwined with various systemic physiological and pathological processes. Alzheimer's disease (AD) is a multifactorial disease, with mitochondrial dysfunction at its core. Although numerous studies have found evidence of mitochondrial transfer in AD models, the precise mechanisms remain unclear. Recent studies have revealed the dynamic transfer of mitochondria in Alzheimer's disease, not only between nerve cells and glial cells, but also between nerve cells and glial cells. In this review, we explore the pathways and mechanisms of mitochondrial transfer in Alzheimer's disease and how these transfer activities contribute to disease progression.

Keywords:  AD treatment; Alzheimer’s disease; mitochondrial dysfunction; mitochondrial transfer; neuroprotection

DOI:  https://doi.org/10.3389/fnagi.2024.1517965
Eur Geriatr Med. 2025 Jan 02.

The role of the circadian timing system in sarcopenia in old age: a scoping review.

Francesco Palmese, Ylenia Druda, Rossella Del Toro, Giorgio Bedogni, Marco Domenicali, Alessandro Silvani.

   PURPOSE: Sarcopenia is a progressive and generalized skeletal muscle disorder, involving the accelerated loss of skeletal muscle mass and function, associated with an increased probability of adverse outcomes including falls. The circadian timing system may be involved in molecular pathways leading to sarcopenia in older adults. We aimed to provide an updated and systematic map of the available evidence on the role of the circadian timing system in sarcopenia, specifically related to the aging process.
METHODS: We developed a scoping review protocol following the PRISMA-ScR guidelines. Searches were conducted on PubMed, Scopus, Web of Science, RESULTS: We identified 373 papers from three online databases, screened 97 for full-text analysis. and selected 37 papers for inclusion. These papers included 17 primary research studies on human persons, focusing on cortisol and melatonin secretion, rest-activity rhythms, chrono-exercise, and chrono-dietary regimens, 9 primary research studies on animal models (mice, rats, fruit flies) focusing on direct expression measurement or mutations of core clock genes, and 11 narrative reviews.
CONCLUSION: While several reports supported the role of the circadian timing system in sarcopenia, specifically related to the aging process, the available evidence is fragmented and limited. The field is thus open to preclinical and clinical research that addresses the wide knowledge gaps in the available evidence, taking advantage of what has already been published to optimize and refine experimental and clinical protocols.

Keywords:  Aging; Circadian; Physical performance; Skeletal muscle force; Skeletal muscle mass

DOI:  https://doi.org/10.1007/s41999-024-01129-0
Front Cell Infect Microbiol. 2024 ;14 1501949

Connecting dots of long COVID-19 pathogenesis: a vagus nerve- hypothalamic-pituitary- adrenal-mitochondrial axis dysfunction.

Marta Camici, Giulia Del Duca, Anna Clelia Brita, Andrea Antinori.

  The pathogenesis of long COVID (LC) still presents many areas of uncertainty. This leads to difficulties in finding an effective specific therapy. We hypothesize that the key to LC pathogenesis lies in the presence of chronic functional damage to the main anti-inflammatory mechanisms of our body: the three reflexes mediated by the vagus nerve, the hypothalamic-pituitary-adrenal (HPA) hormonal axis, and the mitochondrial redox status. We will illustrate that this neuro-endocrine-metabolic axis is closely interconnected and how the SARS-CoV-2 can damage it at all stages through direct, immune-inflammatory, epigenetic damage mechanisms, as well as through the reactivation of neurotropic viruses. According to our theory, the direct mitochondrial damage carried out by the virus, which replicates within these organelles, and the cellular oxidative imbalance, cannot be countered in patients who develop LC. This is because their anti-inflammatory mechanisms are inconsistent due to reduced vagal tone and direct damage to the endocrine glands of the HPA axis. We will illustrate how acetylcholine (ACh) and cortisol, with its cytoplasmatic and cellular receptors respectively, are fundamental players in the LC process. Both Ach and cortisol play multifaceted and synergistic roles in reducing inflammation. They achieve this by modulating the activity of innate and cell-mediated immunity, attenuating endothelial and platelet activation, and modulating mitochondrial function, which is crucial for cellular energy production and anti-inflammatory mechanisms. In our opinion, it is essential to study the sensitivity of the glucocorticoids receptor in people who develop LC and whether SARS-CoV-2 can cause long-term epigenetic variations in its expression and function.

Keywords:  adrenergic anti-inflammatory reflex; cholinergic anti-inflammatory reflex; cortisol; glucocorticoids receptor; hypothalamic-pituitary-adrenal axis reflex; long COVID; mitochondrial dysfunction; vagus nerve dysfunction

DOI:  https://doi.org/10.3389/fcimb.2024.1501949