• BMB Reports
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• v.41 no.11
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• pp.751-756
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• 2008

Aging and cancer both occur as a result of accumulated cellular damage, and both are related to the regulation of specific genes in the damage response. Recent research has unveiled connections between the mechanisms of aging and cancer, but how to prevent the development of cancer and increase longevity remain unknown. SIRT1 (the mammalian Sir2), which has $NAD^+$-dependent class III histone deacetylase activity, may be a key gene linking the modulation of cancer and aging. SIRT1 has broad biological functions in growth regulation, stress response, tumorigenesis, endocrine signaling, and extended lifespan. Here, we focus on the current knowledge regarding the role of SIRT1 in aging and cancer, and discuss the implications of SIRT1 as a therapeutic target for the optimal balance between anti-aging and anti-cancer activities.

• Molecules and Cells
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• v.44 no.7
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• pp.425-432
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• 2021

Aging is associated with functional and structural declines in organisms over time. Organisms as diverse as the nematode Caenorhabditis elegans and mammals share signaling pathways that regulate aging and lifespan. In this review, we discuss recent combinatorial approach to aging research employing C. elegans and mammalian systems that have contributed to our understanding of evolutionarily conserved aging-regulating pathways. The topics covered here include insulin/IGF-1, mechanistic target of rapamycin (mTOR), and sirtuin signaling pathways; dietary restriction; autophagy; mitochondria; and the nervous system. A combinatorial approach employing high-throughput, rapid C. elegans systems, and human model mammalian systems is likely to continue providing mechanistic insights into aging biology and will help develop therapeutics against age-associated disorders.

• Biomolecules & Therapeutics
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• v.27 no.3
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• pp.283-289
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• 2019

Brain aging induces neuropsychological changes, such as decreased memory capacity, language ability, and attention; and is also associated with neurodegenerative diseases. However, most of the studies on brain aging are focused on neurons, while senescence in astrocytes has received less attention. Astrocytes constitute the majority of cell types in the brain and perform various functions in the brain such as supporting brain structures, regulating blood-brain barrier permeability, transmitter uptake and regulation, and immunity modulation. Recent studies have shown that SIRT1 and SIRT2 play certain roles in cellular senescence in peripheral systems. Both SIRT1 and SIRT2 inhibitors delay tumor growth in vivo without significant general toxicity. In this study, we investigated the role of tenovin-1, an inhibitor of SIRT1 and SIRT2, on rat primary astrocytes where we observed senescence and other functional changes. Cellular senescence usually is characterized by irreversible cell cycle arrest and induces senescence- associated ${\beta}$-galactosidase (SA-${\beta}$-gal) activity. Tenovin-1-treated astrocytes showed increased SA-${\beta}$-gal-positive cell number, senescence-associated secretory phenotypes, including IL-6 and IL-$1{\beta}$, and cell cycle-related proteins like phospho-histone H3 and CDK2. Along with the molecular changes, tenovin-1 impaired the wound-healing activity of cultured primary astrocytes. These data suggest that tenovin-1 can induce cellular senescence in astrocytes possibly by inhibiting SIRT1 and SIRT2, which may play particular roles in brain aging and neurodegenerative conditions.

• BMB Reports
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• v.52 no.1
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• pp.1-2
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• 2019

• Molecules and Cells
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• v.46 no.7
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• pp.417-419
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• 2023

• BMB Reports
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• v.44 no.5
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• pp.291-297
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• 2011

Aging is one of the most complicated biological processes in all species. A number of different model organisms from yeast to monkeys have been studied to understand the aging process. Until recently, many different age-related genes and age-regulating cellular pathways, such as insulin/IGF-1-like signal, mitochondrial dysfunction, Sir2 pathway, have been identified through classical genetic studies. Parallel to genetic approaches, genome-wide approaches have provided valuable insights for the understanding of molecular mechanisms occurring during aging. Gene expression profiling analysis can measure the transcriptional alteration of multiple genes in a genome simultaneously and is widely used to elucidate the mechanisms of complex biological pathways. Here, current global gene expression profiling studies on normal aging and age-related genetic/environmental interventions in widely-used model organisms are briefly reviewed.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.31 no.2
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• pp.66-70
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• 2020

Background and Objectives Presbyphonia is characterized by hoarse, breathy, weak vocal intensity. Extracellular matrix (ECM) in lamina propria (LP) of the vocal folds play an important role in voice production, and change of ECM according to the aging leads to the presbyphonia. The aim of this study was to investigate the histologic analysis of aging vocal fold of rat. Materials and Method Six and twenty two months old Sprague-Dawley rats (n=8, each group) were used and classified into young (six months old rats) and old (twenty two months old rats) group. Histologic analysis and immunohistochemical staining for ECM of LP were performed. Results Overall cellular density was significantly decreased in old rat group. Elastin fibers of LP were significantly decreased in old rat group. Type I collagen was significantly increased in old rat group. Type III collagen did not show significant difference. Hyaluronic acids did not show significant difference in Alcian blue staining and immunohistochemical staining. Conclusion Decreased general cellular density and elastin fiber and increased type I collagen were observed in the LP of vocal folds of aging rats. These ECM changes might to contribute the aging voice.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.41 no.2
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• pp.135-141
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• 2015

Cell senescence can be identified by cellular changes that occur as a result of intrinsic aging and/or diseases. In case of skin cells, aging and cell senescence caused by external factors results in cessation of cell proliferation and cellular malfunction, which, in turn, accelerates skin aging. In this study, inhibition of cell senescence and enhancement of cell function were studied using cordycepin to evaluate the potential for skin anti-aging agent. By comparing with the number of senescence associated with ${\beta}$-galactosidase (SA-${\beta}$-gal) positive cells in young and replicative aged human fibroblasts, it was found that replicative aged cells showed higher expression of ${\beta}$-galactosidase. Treatment of cordycepin - known as an anti-oxidative and anti-inflammatory agent - reduced ${\beta}$-galactosidase expression in senescent cells and enhanced cell survival in serum-free culture condition. Cordycepin also showed superb inhibition of ROS, which is another indicator of cell senescence. The results of this study proved the anti-aging effect of cordycepin on human fibroblasts and also proposed a possibility of its use as an anti-aging cosmetic ingredient.

• Molecules and Cells
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• v.40 no.9
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• pp.607-612
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• 2017

When mammalian cells and animals face a variety of internal or external stresses, they need to make homeostatic changes so as to cope with various stresses. To this end, mammalian cells are equipped with two critical stress responses, autophagy and cellular senescence. Autophagy and cellular senescence share a number of stimuli including telomere shortening, DNA damage, oncogenic stress and oxidative stress, suggesting their intimate relationship. Autophagy is originally thought to suppress cellular senescence by removing damaged macromolecules or organelles, yet recent studies also indicated that autophagy promotes cellular senescence by facilitating the synthesis of senescence-associated secretory proteins. These seemingly opposite roles of autophagy may reflect a complex picture of autophagic regulation on cellular senescence, including different types of autophagy or a unique spatiotemporal activation of autophagy. Thus, a better understanding of autophagy process will lead us to not only elucidate the conundrum how autophagy plays dual roles in the regulation of cellular senescence but also helps the development of new therapeutic strategies for many human diseases associated with cellular senescence. We address the pro-senescence and anti-senescence roles of autophagy while focusing on the potential mechanistic aspects of this complex relationship between autophagy and cellular senescence.

• Preventive Nutrition and Food Science
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• v.22 no.2
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• pp.81-89
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• 2017

Healthy aging has become a major goal of public health. Many studies have provided evidence and theories to explain molecular mechanisms of the aging process. Recent studies suggest that epigenetic mechanisms are responsible for life span and the progression of aging. Epigenetics is a fascinating field of molecular biology, which studies heritable modifications of DNA and histones that regulate gene expression without altering the DNA sequence. DNA methylation is a major epigenetic mark that shows progressive changes during aging. Recent studies have investigated aging-related DNA methylation as a biomarker that predicts cellular age. Interestingly, growing evidence proposes that nutrients play a crucial role in the regulation of epigenetic modifiers. Because various nutrients and their metabolites function as substrates or cofactors for epigenetic modifiers, nutrition can modulate or reverse epigenetic marks in the genome as well as expression patterns. Here, we will review the results on aging-associated epigenetic modifications and the possible mechanisms by which nutrition, including nutrient availability and bioactive compounds, regulate epigenetic changes and affect aging physiology.