Aging: Central role for autophagy and the lysosomal degradative system

Rajawat, Yogendra Singh; Hilioti, Zoe; Bossis, Ioannis

doi:10.1016/j.arr.2009.05.001

Cited by 225 publications

(169 citation statements)

References 185 publications

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“…One of the hallmarks of aging is the generation of damaged organelles and molecular aggregates which may be removed by autophagy, and the decline in autophagic capacity is involved in the development of age‐related diseases (see, for example, Rajawat et al ., 2009). In kidney, decreased autophagy has been related to glomerulosclerosis, tubular atrophy, and interstitial fibrosis, and two different renal cell types have been reported to display autophagic activity depending on the physiological conditions: podocytes and PCT cells (Hartleben et al ., 2010; Kume et al ., 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Besides the potential role of CR in mitigating oxidative stress, autophagy is also a crucial phenomenon to explain CR effects on longevity and healthy aging (Rajawat et al ., 2009; Speakman & Mitchell, 2011 and Madeo et al ., 2015). By this mechanism, different aged subcellular structures which accumulate molecular damage are degraded through a lysosomal pathway and the resulting products are released into the cytosol for recycling or to supply energy during starvation periods (Cuervo, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice

et al. 2016

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SummaryCalorie restriction (CR) has been repeatedly shown to prevent cancer, diabetes, hypertension, and other age‐related diseases in a wide range of animals, including non‐human primates and humans. In rodents, CR also increases lifespan and is a powerful tool for studying the aging process. Recently, it has been reported in mice that dietary fat plays an important role in determining lifespan extension with 40% CR. In these conditions, animals fed lard as dietary fat showed an increased longevity compared with mice fed soybean or fish oils. In this paper, we study the effect of these dietary fats on structural and physiological parameters of kidney from mice maintained on 40% CR for 6 and 18 months. Analyses were performed using quantitative electron microcopy techniques and protein expression in Western blots. CR mitigated most of the analyzed age‐related parameters in kidney, such as glomerular basement membrane thickness, mitochondrial mass in convoluted proximal tubules and autophagic markers in renal homogenates. The lard group showed improved preservation of several renal structures with aging when compared to the other CR diet groups. These results indicate that dietary fat modulates renal structure and function in CR mice and plays an essential role in the determination of health span in rodents.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice

et al. 2016

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“…Aging is an irreversible process characterized by the progressive loss of physiological and structural integrity of cells and organisms (Rajawat et al 2009;López-Otín et al 2013). In humans, besides increasing vulnerability to death, it deepens the risk of cancer and cardiovascular and neurodegenerative diseases (López-Otin et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Senescence associated secretory phenotype profile from primary lung mice fibroblasts depends on the senescence induction stimuli

Maciel-Barón

Morales-Rosales

Aquino-Cruz

et al. 2016

AGE

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Cellular senescence is a multifactorial phenomenon of growth arrest and distorted function, which has been recognized as an important feature during tumor suppression mechanisms and a contributor to aging. Senescent cells have an altered secretion pattern called Senescence-Associated Secretory Phenotype (SASP) that comprises a complex mix of factors including cytokines, growth factors, chemokines, and matrix metalloproteinases. SASP has been related with local inflammation that leads to cellular transformation and neurodegenerative diseases. Various pathways for senescence induction have been proposed; the most studied is replicative senescence due to telomere attrition called replicative senescence (RS). However, senescence can be prematurely achieved when cells are exposed to diverse stimuli such as oxidative stress (stressinduced premature senescence, SIPS) or proteasome inhibition (proteasome inhibition-induced premature senescence, PIIPS). SASP has been characterized in RS and SIPS but not in PIIPS. Hence, our aim was to determine SASP components in primary lung fibroblasts obtained from CD-1 mice induced to senescence by PIIPS and compare them to RS and SIPS. Our results showed important variations in the 62 cytokines analyzed, while SIPS and RS showed an increase in the secretion of most cytokines, and in PIIPS only 13 were incremented. Variations in glutathione-redox balance were also observed in SIPS and RS, and not in PIIPS. All senescence types SASP displayed a pro-inflammatory profile and increased proliferation in L929 mice fibroblasts exposed to SASP. However, the behavior observed was not exactly the same, suggesting that the senescence induction pathway might encompass dissimilar responses in adjacent cells and promote different outcomes.

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“…Aging is a multifactorial process and attempts at understanding the fundamental causes of aging are limited by the complexity of the problem (Kirkwood, 2005;Rajawat et al, 2009). However, studying aging processes at the cellular and molecular levels is complicated and subjected to confounding experimental and environmental factors (Dice, 1993).…”

Section: Introductionmentioning

confidence: 99%

“…These include damage to DNA or inability to repair, damage to cell organelles and tissues by free radicals of oxygen, protein cross-linking and the limited ability of the cellular turnover mechanisms to remove such damaged structures and molecules. The progressive accumulation of such damage at a level that inhibits or disrupts normal physiological function may lead to progressive aging changes and senescence (Rajawat et al, 2009). Moreover, it has been demonstrated that free radicals or reactive 4 oxygen species (ROS) accumulate over time causing progressive deterioration in the function of cells, tissues and organ systems, which may ultimately cause the death of cells and damage to a system.…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E and its role in aging and survival

Bonomini

Filippini

Hayek

et al. 2010

Experimental Gerontology

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The study of biological aging has seen spectacular progress in the last decade and markers are increasingly employed for understanding physiological processes that change with age. Recently, it has been demonstrated that apolipoprotein E (apoE) has a major impact on longevity, but its mechanisms are still not fully understood. ApoE-deficient (E o ) mice have proved to be a very popular model for studying spontaneous hypercholesterolemia and the subsequent development of atherosclerotic lesions, but only limited data are available with regard to aging and aging changes.We used this murine model to better characterize the involvement of apoE in aging and to evaluate its role in the maintenance of normal organ morphology. Our results show that E 0 mice at different ages (6, 12, 20 weeks old) developed age-dependent morphological and biochemical alterations, including fibrosis (newly formed collagen), pro-inflammatory cytokine (IL-6 and iNOS), lipofuscin accumulation, and decrease of antioxidant enzymes (superoxide dismutase and catalase) in several organs (kidney, liver and heart). It is significant that the observed degenerative findings in E 0 mice at different ages (6, 12, 20 weeks old) were not identified in control mice (C57BL), at 6, 12 and 20 weeks of age. Consequently, since these mice showed enzymatic and structural alterations, normally linked to the age, such as increase of lipofuscin, pro-inflammatory cytokines and decrease of antioxidant enzymes, we can conclude that apoE is a useful player in studies of longevity and age-related diseases, such as inflammatory status and atherosclerosis that are known risk factors for functional decline and early mortality. Moreover, it is possible that apoE may also play a role in other pathological conditions including, for example, cancer, rheumatoid arthritis and macular degeneration.

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Aging: Central role for autophagy and the lysosomal degradative system

Cited by 225 publications

References 185 publications

Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice

Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice

Senescence associated secretory phenotype profile from primary lung mice fibroblasts depends on the senescence induction stimuli

Apolipoprotein E and its role in aging and survival

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