• Title/Summary/Keyword: lipofuscin granule

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Lipofuscin Granule Accumulation Requires Autophagy Activation

  • Seon Beom Song;Woosung Shim;Eun Seong Hwang
    • Molecules and Cells
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    • v.46 no.8
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    • pp.486-495
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    • 2023
  • Lipofuscins are oxidized lipid and protein complexes that accumulate during cellular senescence and tissue aging, regarded as markers for cellular oxidative damage, tissue aging, and certain aging-associated diseases. Therefore, understanding their cellular biological properties is crucial for effective treatment development. Through traditional microscopy, lipofuscins are readily observed as fluorescent granules thought to accumulate in lysosomes. However, lipofuscin granule formation and accumulation in senescent cells are poorly understood. Thus, this study examined lipofuscin accumulation in human fibroblasts exposed to various stressors. Our results substantiate that in glucose-starved or replicative senescence cells, where elevated oxidative stress levels activate autophagy, lipofuscins predominately appear as granules that co-localize with autolysosomes due to lysosomal acidity or impairment. Meanwhile, autophagosome formation is attenuated in cells experiencing oxidative stress induced by a doxorubicin pulse and chase, and lipofuscin fluorescence granules seldom manifest in the cytoplasm. As Torin-1 treatment activates autophagy, granular lipofuscins intensify and dominate, indicating that autophagy activation triggers their accumulation. Our results suggest that high oxidative stress activates autophagy but fails in lipofuscin removal, leaving an abundance of lipofuscin-filled impaired autolysosomes, referred to as residual bodies. Therefore, future endeavors in treating lipofuscin pathology-associated diseases and dysfunctions through autophagy activation demand meticulous consideration.

Effects of the Exercise Training on Aging Heart in Rat I. Long Term Endurance Exercise (운동훈련이 흰쥐 노화심근에 미치는 영향 I. 장기간 지구력 운동 훈련)

  • 박원학;이상선;이용덕
    • Biomedical Science Letters
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    • v.2 no.1
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    • pp.71-90
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    • 1996
  • There is considerable current interest in the effect of regular vigorous exercise and in particular endurance-running as a possible measure in improving myocardial function. Some data indicate that the aging heart may actually suffer from vigorous endurance exercise. On the contrary appropriate exercise in aged animals improves myocardial function and aerobic energy metabolism. So far there is relatively little data to indicate that endurance exercise is in fact beneficial in improving myocardial function or damaging to heart of aged animals. The present investigation aimed to study the possible effect of a long range treadmill training program on the heart in aging rats. Male rats aged 3, 10, and 20 months were divided at random into a control (sedentary) and an exercise group. The training group was exercised for 5 days a week on an automated treadmill for 20minutes at 18m/min over a period of 5 months. The exercise regimen of our experiments did not cause any significant changes in the tissues and ultrastructural as com-pared with sedentary age-matched control. Tissues and ultrastructures of myocardial cells in trained group aged 8 months are intact and well organized as well as sedentary control group. Age associated tissue and ultrastructural changes of trained group aged 15 months included : an increase in transformed mitochondria, vacuoles, lysosomes, lipid droplets and early lipofuscin. But the trained heart did not show significant difference in tissue and ultrastructural properties from those of sedentary controls. Endurance-trained group aged 25 months showed significant qualitative tissue and ultrastructural difference as compared with age-matched controls. In addition to those found in 25 months control group, focal necrosis, myofibril fraying, hypercontraction band, seperation of intercalated discs, degenerating nucleus and infiltration of collagenous fiber into myocyte were noted in trained 25 months group. The stereological examination of the mi-crographs disclosed no significant difference in the myoflbril, mitochondrion, sarcotubule and in-terstitium volume density and surface density of mitochondrial cristae and numerical density of mitochondria between trained and control group aged 8 and 15 months. In the trained 25 months group, significant increase in volume density of interstitium, lipofucsin granule were shown as compared to untrained age-matched control. On the other hand, significant decrease in mitochondrion volume density was shown. The myofibril volume density did not differ between trained and control group although trained group showed slight increase. From the data obtained a reduced mitochondria/myofibrils ratio was found in trained rat heart aged 25 months and there was no difference between trained and control rat aged 15 months. But a slight but not significant increase was found in the trained group aged 8 months as compared with same age control group. Such increase in the ratio in young animals is considered to be of great importance to cardiac pumping and adaptability. Whereas such adaptations don't seem to occur in aged heart muscle. This study proposed that repeated endurance exercise do not cause any significant qualitative and quantitative ultrastructural change of heart muscle in young(3months) and adult (10months) suggesting that the heart is able to adapt to the exercise. On the contrary, the repeated endurance exercise stress may actually induce degenerative changes in the aged heart muscle(20months).

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