• Biotechnology and Bioprocess Engineering:BBE
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• v.6 no.4
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• pp.231-236
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• 2001

How much do we know about the biology of aging from cell culture studies Most normal somatic cells have a finite potential to divide due to a process termed cellular or replicative senescence. A growing body evidence suggests that senescence evolved to protect higher eu-karyotes, particularly mammals, from developing cancer, We now know that telomere shortening due to the biochemistry of DNA replication, induces replicative senescence in human cells. How-ever in rodent cells, replicative senescence occurs despite very long telomeres. Recent findings suggest that replicative senescence is just the tip of the iceberg of a more general process termed cellular senescence. It appears that cellular senescence is a response to potentially oncogenic in-sults, including oxidative damage. In young orgainsms, growth arrest by cell senescence sup-presses tumor development, but later in life, due to the accumulation of senescent cells which se-cret factors that can disrupt tissues during aging, cellular senescence promotes tumorigenesis. Therefore, antagonistic pleiotropy may explain, if not in whole the apparently paradoxical effects of cellular senescence, though this still remains an open question.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.291-312
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• 2003

Reactive oxygen species are capable of damaging biomolecules such as lipids, proteins, and DNA, which can not only lead to various diseases, but also oxidative damage resulting aging. In our previous study, Cercis chinensis (Leguminosae) showed a potent antioxidant activity. Nineteen compounds were isolated through antioxidant activity-guided fractionation. The C. chinensis extract and some of the constituents exhibited a potent antioxidant activity on the free radicals and lipid peroxidation and a notable protective effect on the t-BuOOH induced oxidative damage. In vivo test of skin damage induced by UVB irradiation, the extract of C. chinensis and a constituent, piceatannol, exhibited a significant protective effect. The life-span of the HEK-N/F cells were extended by 1.21-2.12 fold as a result of the continuous administration of 3 $\mu\textrm{g}$/ml of the C. chinensis extract and the active constituents compared to that of the control. These observations were attributed to the inhibitory effect of the C. chinensis extract and its constituents on the age-dependent shortening of the telomere. Thus, C. chinensis was demonstrated to protect the skin cells against oxidative stress and inhibit thereby the cellular aging, followed by expectation as 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.

• Proceedings of the SCSK Conference
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• 2003.09b
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• pp.117-138
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• 2003

Reactive oxygen species are capable of damaging biomolecules such as lipids, proteins, and DNA, which can not only lead to various diseases, but also oxidative damage resulting aging. In our previous study, Cercis chinensis (Leguminosae) showed a potent antioxidant activity. Nineteen compounds were isolated through antioxidant activity-guided fractionation. The C. chinensis extract and some of the constituents exhibited a potent antioxidant activity on the free radicals and lipid peroxidation and a notable protective effect on the t-BuOOH induced oxidative damage. In vivo test of skin damage induced by UVB irradiation, the extract of C. chinensis and a constituent, piceatannol, exhibited a significant protective effect. The life-span of the HEK-N/F cells were extended by 1.21-2.12 fold as a result of the continuous administration of 3 $\mu\textrm{g}$/ml of the C. chinensis extract and the active constituents compared to that of the control. These observations were attributed to the inhibitory effect of the C. chinensis extract and its constituents on the age-dependent shortening of the telomere. Thus, C. chinensis was demonstrated to protect the skin cells against oxidative stress and inhibit thereby the cellular aging, followed by expectation as antiaging cosmetic ingredient.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.27 no.1
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• pp.45-57
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• 2014

Objective : The purpose of this study is to understand aging and skin aging with both western and Korean medicine. Methods : We investigated the comprehension of general aging and skin aging in both western and Korean medicine through literature review. Result : The results are as follows. 1. Aging in western is a complex process influenced by telomere shortening and damage to cellular DNA. In Korean medicine, it is supposed that decline of interaction between yin(陰) and yang(陽) makes aging. 2. Skin aging in western medicine consists of intrinsic aging and extrinsic aging. In Korean medicine, skin aging goes with the aging of whole body and distinctive features of geroderma notice the unbalance of the whole body function. 3. Generally geroderma has decreased development of cells and low immunity, which is the function of kidney(腎) in Korean medicine. Conclusion : Further studies are needed to apply comprehension of skin aging in Korean medicine to clinical stage.

• Journal of Korean Biological Nursing Science
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• v.26 no.2
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• pp.99-110
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• 2024

Purpose: This study reviewed the pathophysiological mechanisms of cellular aging caused by psychological stress and aimed to establish a biobehavioral theoretical framework for nursing interventions to promote autonomic balance based on these mechanisms. Methods: A comprehensive literature review was conducted. Results: A review of the literature showed that the stress response increases the secretion of catecholamines and glucocorticoids, resulting in a greater allostatic load. This load induces inflammatory reactions and oxidative stress, shortening telomere length and damaging mitochondrial DNA, which can lead to cellular aging. Based on this mechanism, a biobehavioral theoretical framework for nursing interventions was established. This framework focuses on delaying or inhibiting the cellular aging process by acting on the stress response stage and improving autonomic balance. Conclusion: According to the proposed biobehavioral theoretical framework, stress-relieving nursing interventions may act on the mechanism of cellular aging caused by stress responses. We believe that this framework could expand our understanding of the biobehavioral aspects of stress and would facilitate efforts to use biomarkers to evaluate the effectiveness of stress-related nursing interventions at the cellular level.

• Molecules and Cells
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• v.37 no.7
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• pp.526-531
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• 2014

Human PARP family consists of 17 members of which PARP-1 is a prominent member and plays a key role in DNA repair pathways. It has an N-terminal DNA-binding domain (DBD) encompassing the nuclear localisation signal (NLS), central automodification domain and C-terminal catalytic domain. PARP-1 accounts for majority of poly-(ADP-ribose) polymer synthesis that upon binding to numerous proteins including PARP itself modulates their activity. Reduced PARP-1 activity in ageing human samples and its deficiency leading to telomere shortening has been reported. Hence for cell survival, maintenance of genomic integrity and longevity presence of intact PARP-1 in the nucleus is paramount. Although localisation of full-length and truncated PARP-1 in PARP-1 proficient cells is well documented, subcellular distribution of PARP-1 fragments in the absence of endogenous PARP-1 is not known. Here we report the differential localisation of PARP-1 Nterminal fragment encompassing NLS in PARP-$1^{+/+}$ and PARP-$1^{-/-}$ mouse embryo fibroblasts by live imaging of cells transiently expressing EGFP tagged fragment. In PARP-$1^{+/+}$ cells the fragment localises to the nuclei presenting a granular pattern. Furthermore, it is densely packaged in the midsections of the nucleus. In contrast, the fragment localises exclusively to the cytoplasm in PARP-$1^{-/-}$ cells. Flourescence intensity analysis further confirmed this observation indicating that the N-terminal fragment requires endogenous PARP-1 for its nuclear transport. Our study illustrates the trafficking role of PARP-1 independently of its enzymatic activity and highlights the possibility that full-length PARP-1 may play a key role in the nuclear transport of its siblings and other molecules.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4517-4525
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• 2016

Background: Sperm DNA damage is underlying aetiology of poor implantation and pregnancy rates but also affects health of offspring and may also result in denovo mutations in germ line and post fertilization. This may result in complex diseases, polygenic disorders and childhood cancers. Childhood cancer like retinoblastoma (RB) is more prevalent in developing countries and the incidence of RB has increased more than three fold in India in the last decade. Recent studies have documented increased incidence of cancers in children born to fathers who consume alcohol in excess and tobacco or who were conceived by assisted conception. The aetiology of childhood cancer and increased disease burden in these children is lin ked to oxidative stress (OS) and oxidative DNA damage( ODD) in sperm of their fathers. Though several antioxidants are in use to combat oxidative stress, the effect of majority of these formulations on DNA is not known. Yoga and meditation cause significant decline in OS and ODD and aid in regulating OS levels such that reactive oxygen speues meditated signal transduction, gene expression and several other physiological functions are not disrupted. Thus, this study aimed to analyze sperm ODD as a possible etiological factor in childhood cancer and role of simple life style interventions like yoga and meditation in significantly decreasing seminal oxidative stress and oxidative DNA damage and thereby decreasing incidence of childhood cancers. Materials and Methods: A total of 131 fathers of children with RB (non-familial sporadic heritable) and 50 controls (fathers of healthy children) were recruited at a tertiary center in India. Sperm parameters as per WHO 2010 guidelines and reactive oxygen species (ROS), DNA fragmentation index (DFI), 8-hydroxy-2'-deoxy guanosine (8-OHdG) and telomere length were estimated at day 0, and after 3 and 6 months of intervention. We also examined the compliance with yoga and meditation practice and smoking status at each follow-up. Results: The seminal mean ROS levels (p<0.05), sperm DFI (p<0.001), 8-OHdG (p<0.01) levels were significantly higher in fathers of children with RB, as compared to controls and the relative mean telomere length in the sperm was shorter. Levels of ROS were significantly reduced in tobacco users (p<0.05) as well as in alcoholics (p<0.05) after intervention. DFI reduced significantly (p<0.05) after 6 months of yoga and meditation practice in all groups. The levels of oxidative DNA damage marker 8-OHdG were reduced significantly after 3 months (p<0.05) and 6 months (p<0.05) of practice. Conclusions: Our results suggest that OS and ODD DNA may contribute to the development of childhood cancer. This may be due to accumulation of oxidized mutagenic base 8OHdG, and elevated MDA levels which results in MDA dimers which are also mutagenic, aberrant methylation pattern, altered gene expression which affect cell proliferation and survival through activation of transcription factors. Increased mt DNA mutations and aberrant repair of mt and nuclear DNA due to highly truncatred DNA repair mechanisms all contribute to sperm genome hypermutability and persistant oxidative DNA damage. Oxidative stress is also associated with genome wide hypomethylation, telomere shortening and mitochondrial dysfunction leading to genome hypermutability and instability. To the best of our knowledge, this is the first study to report decline in OS and ODD and improvement in sperm DNA integrity following adoption of meditation and yoga based life style modification.This may reduce disease burden in next generation and reduce incidence of childhood cancers.