bims-agimec 2024-09-15 papers

Issue of 2024–09–15
seven papers selected by
Metin Sökmen, Ankara Üniversitesi

Methods. 2024 Sep 07. pii: S1046-2023(24)00191-9. [Epub ahead of print]

Exploring the potential of epigenetic clocks in aging research.

Yuduo Hao, Kaiyuan Han, Ting Wang, Junwen Yu, Hui Ding, Fuying Dao.

The process of aging is a notable risk factor for numerous age-related illnesses. Hence, a reliable technique for evaluating biological age or the pace of aging is crucial for understanding the aging process and its influence on the progression of disease. Epigenetic alterations are recognized as a prominent biomarker of aging, and epigenetic clocks formulated on this basis have been shown to provide precise estimations of chronological age. Extensive research has validated the effectiveness of epigenetic clocks in determining aging rates, identifying risk factors for aging, evaluating the impact of anti-aging interventions, and predicting the emergence of age-related diseases. This review provides a detailed overview of the theoretical principles underlying the development of epigenetic clocks and their utility in aging research. Furthermore, it explores the existing obstacles and possibilities linked to epigenetic clocks and proposes potential avenues for future studies in this field.

Keywords: Aging; Biological age; Epigenetic age; Epigenetic age acceleration; Epigenetic clock

DOI: https://doi.org/10.1016/j.ymeth.2024.09.001

Int J Mol Sci. 2024 Sep 07. pii: 9705. [Epub ahead of print]25(17):

The Role of Molecular and Cellular Aging Pathways on Age-Related Hearing Loss.

Tuba Ege, Litao Tao, Brian J North.

Aging, a complex process marked by molecular and cellular changes, inevitably influences tissue and organ homeostasis and leads to an increased onset or progression of many chronic diseases and conditions, one of which is age-related hearing loss (ARHL). ARHL, known as presbycusis, is characterized by the gradual and irreversible decline in auditory sensitivity, accompanied by the loss of auditory sensory cells and neurons, and the decline in auditory processing abilities associated with aging. The extended human lifespan achieved by modern medicine simultaneously exposes a rising prevalence of age-related conditions, with ARHL being one of the most significant. While our understanding of the molecular basis for aging has increased over the past three decades, a further understanding of the interrelationship between the key pathways controlling the aging process and the development of ARHL is needed to identify novel targets for the treatment of AHRL. The dysregulation of molecular pathways (AMPK, mTOR, insulin/IGF-1, and sirtuins) and cellular pathways (senescence, autophagy, and oxidative stress) have been shown to contribute to ARHL. However, the mechanistic basis for these pathways in the initiation and progression of ARHL needs to be clarified. Therefore, understanding how longevity pathways are associated with ARHL will directly influence the development of therapeutic strategies to treat or prevent ARHL. This review explores our current understanding of the molecular and cellular mechanisms of aging and hearing loss and their potential to provide new approaches for early diagnosis, prevention, and treatment of ARHL.

Keywords: cochlear aging; hair cells; hearing loss; mitochondrial dysfunction; senescence; sirtuins

DOI: https://doi.org/10.3390/ijms25179705

Mech Ageing Dev. 2024 Sep 10. pii: S0047-6374(24)00088-5. [Epub ahead of print] 111988

Adipose tissue senescence: biological changes, hallmarks and therapeutic approaches.

Yajuan Zhang, Yaoyao Jiang, Xiaoyue Yang, Yumei Huang, An Pan, Yunfei Liao.

Adipose tissue (AT), the largest energy storage reservoir and endocrine organ, plays a crucial role in regulating systemic energy metabolism. As one of the most vulnerable tissues during aging, the plasticity of AT is impaired. With age, AT undergoes redistribution, characterized by expansion of visceral adipose tissue (VAT) and reduction of peripheral subcutaneous adipose tissue (SAT). Additionally, age-related changes in AT include reduced adipogenesis of white adipocytes, decreased proliferation and differentiation capacity of mesenchymal stromal/stem cells (MSCs), diminished thermogenic capacity in brown/beige adipocytes, and dysregulation of immune cells. Specific and sensitive hallmarks enable the monitoring and evaluation of the biological changes associated with aging. In this study, we have innovatively proposed seven characteristic hallmarks of AT senescence, including telomere attrition, epigenetic alterations, genomic instability, mitochondrial dysfunction, disabled macroautophagy, cellular senescence, and chronic inflammation, which are intricately interconnected and mutually regulated. Finally, we discussed anti-aging strategies targeting AT, offering insights into mitigating or delaying metabolic disturbances caused by AT senescence.

Keywords: Adipose tissue; Aging; Anti-aging strategies; Hallmarks; Senescence

DOI: https://doi.org/10.1016/j.mad.2024.111988

Nutrients. 2024 Aug 24. pii: 2835. [Epub ahead of print]16(17):

Exploring the Geroprotective Potential of Nutraceuticals.

Nadia Alejandra Rivero-Segura, Emmanuel Alejandro Zepeda-Arzate, Selma Karime Castillo-Vazquez, Patrick Fleischmann-delaParra, Jessica Hernández-Pineda, Edgar Flores-Soto, Paola García-delaTorre, Edgar Antonio Estrella-Parra, Juan Carlos Gomez-Verjan.

Aging is the result of the accumulation of a wide variety of molecular and cellular damages over time, meaning that "the more damage we accumulate, the higher the possibility to develop age-related diseases". Therefore, to reduce the incidence of such diseases and improve human health, it becomes important to find ways to combat such damage. In this sense, geroprotectors have been suggested as molecules that could slow down or prevent age-related diseases. On the other hand, nutraceuticals are another set of compounds that align with the need to prevent diseases and promote health since they are biologically active molecules (occurring naturally in food) that, apart from having a nutritional role, have preventive properties, such as antioxidant, anti-inflammatory and antitumoral, just to mention a few. Therefore, in the present review using the specialized databases Scopus and PubMed we collected information from articles published from 2010 to 2023 in order to describe the role of nutraceuticals during the aging process and, given their role in targeting the hallmarks of aging, we suggest that they are potential geroprotectors that could be consumed as part of our regular diet or administered additionally as nutritional supplements.

Keywords: aging; bioactive compounds; geroprotectors; hallmarks of aging; nutraceuticals

DOI: https://doi.org/10.3390/nu16172835

Geroscience. 2024 Sep 13.

Coffee consumption, cancer, and healthy aging: epidemiological evidence and underlying mechanisms.

Setor K Kunutsor, Andrea Lehoczki, Jari A Laukkanen.

This comprehensive review examines the role of coffee consumption in promoting healthy aging and its potential impact on cancer prevention. Previous research has shown that moderate coffee intake may contribute to extending healthspan and enhancing longevity through beneficial effects on cardiometabolic health and key biological processes involved in aging. However, the relationship between coffee consumption and cancer risk remains controversial. This review synthesizes longitudinal observational and interventional data on the effects of coffee consumption on overall and site-specific cancers, explores underlying biological mechanisms, and discusses clinical and public health implications. Additionally, the review highlights evidence from Mendelian randomization (MR) studies to assess potential causal relationships. Our findings suggest that coffee consumption is associated with a reduced risk of several cancers, including skin, liver, prostate, and endometrial cancers, and may also lower cancer recurrence rates, particularly in colorectal cancer. These protective associations appear consistent across different demographic groups, with the most significant benefits observed at consumption levels of three or more cups per day. However, evidence is inconclusive for many other cancers, and coffee consumption is consistently linked to an increased risk of lung cancer. MR studies generally do not support a strong causal relationship for most cancers, though some suggest potential protective effects for hepatocellular, colorectal, and possibly prostate cancers, with mixed results for ovarian cancer and an increased risk for esophageal cancer and multiple myeloma. The protective effect of coffee on liver and prostate cancer is supported by both observational and MR studies. The potential anti-cancer benefits of coffee are attributed to its bioactive compounds, such as caffeine, chlorogenic acids, and diterpenes, which possess antioxidant and anti-inflammatory properties. These compounds may reduce oxidative stress, inhibit cancer cell proliferation, induce apoptosis, and modulate hormone levels. The review emphasizes the need for further research to clarify dose-response relationships, causal associations, and the biological mechanisms underlying these associations. While coffee consumption appears to contribute to cancer prevention and healthy aging, caution is warranted due to the increased risk of certain cancers, highlighting the complexity of its health effects.

Keywords: Caffeine; Cancer; Coffee consumption; Healthspan; Longevity; Mendelian randomization; Mortality

DOI: https://doi.org/10.1007/s11357-024-01332-8

Front Aging Neurosci. 2024 ;16 1453710

c-Jun N-terminal kinase signaling in aging.

Yihao Li, Li You, Eugenie Nepovimova, Vojtech Adam, Zbynek Heger, Klaudia Jomova, Marian Valko, Qinghua Wu, Kamil Kuca.

Aging encompasses a wide array of detrimental effects that compromise physiological functions, elevate the risk of chronic diseases, and impair cognitive abilities. However, the precise underlying mechanisms, particularly the involvement of specific molecular regulatory proteins in the aging process, remain insufficiently understood. Emerging evidence indicates that c-Jun N-terminal kinase (JNK) serves as a potential regulator within the intricate molecular clock governing aging-related processes. JNK demonstrates the ability to diminish telomerase reverse transcriptase activity, elevate β-galactosidase activity, and induce telomere shortening, thereby contributing to immune system aging. Moreover, the circadian rhythm protein is implicated in JNK-mediated aging. Through this comprehensive review, we meticulously elucidate the intricate regulatory mechanisms orchestrated by JNK signaling in aging processes, offering unprecedented molecular insights with significant implications and highlighting potential therapeutic targets. We also explore the translational impact of targeting JNK signaling for interventions aimed at extending healthspan and promoting longevity.

Keywords: JNK; aging; longevity; molecular insights; therapeutic targets

DOI: https://doi.org/10.3389/fnagi.2024.1453710

Ren Fail. 2024 Dec;46(2): 2398712

Podocyte senescence: from molecular mechanisms to therapeutics.

Qian Zhao, Yongzhang Huang, Ningying Fu, Caixia Cui, Xuan Peng, Haiyan Kang, Jie Xiao, Guibao Ke.

As an important component of the glomerular filtration membrane, the state of the podocytes is closely related to kidney function, they are also key cells involved in aging and play a central role in the damage caused by renal aging. Therefore, understanding the aging process of podocytes will allow us to understand their susceptibility to injury and identify targeted protective mechanisms. In fact, the process of physiological aging itself can induce podocyte senescence. Pathological stresses, such as oxidative stress, mitochondrial damage, secretion of senescence-associated secretory phenotype, reduced autophagy, oncogene activation, altered transcription factors, DNA damage response, and other factors, play a crucial role in inducing premature senescence and accelerating aging. Senescence-associated-β-galactosidase (SA-β-gal) is a marker of aging, and β-hydroxybutyric acid treatment can reduce SA-β-gal activity to alleviate cellular senescence and damage. In addition, CCAAT/enhancer-binding protein-α, transforming growth factor-β signaling, glycogen synthase kinase-3β, cycle-dependent kinase, programmed cell death protein 1, and plasminogen activator inhibitor-1 are closely related to aging. The absence or elevation of these factors can affect aging through different mechanisms. Podocyte injury is not an independent process, and injured podocytes interact with the surrounding epithelial cells or other kidney cells to mediate the injury or loss of podocytes. In this review, we discuss the manifestations, molecular mechanisms, biomarkers, and therapeutic drugs for podocyte senescence. We included elamipretide, lithium, calorie restriction, rapamycin; and emerging treatment strategies, such as gene and immune therapies. More importantly, we summarize how podocyte interact with other kidney cells.

Keywords: Podocyte senescence; biomarkers; intervention targets; molecular mechanisms

DOI: https://doi.org/10.1080/0886022X.2024.2398712