Autophagy and Aging: The Importance of Maintaining "Clean" Cells

Cuervo, Ana María; Bergamini, Ettore; Brunk, Ulf T.; Dröge, Wulf; Ffrench, Martine; Terman, Alexei

doi:10.4161/auto.1.3.2017

Cited by 740 publications

(623 citation statements)

References 141 publications

(162 reference statements)

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“…Recent evidence suggests that regular day-long periods of starvation may, by stimulating autophagy, help to "keep cells clean" and be beneficial and prolong life (Cuervo et al, 2005). …”

Section: The Role Of Lysosomes In Intracellular Iron Metabolismmentioning

confidence: 99%

The role of lysosomes in iron metabolism and recycling

Kurz

Eaton

Brunk

2011

The International Journal of Biochemistry & Cell Biology

Self Cite

175

134

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Iron is the most abundant transition metal in the earths crust. It cycles easily between ferric (oxidized; Fe(III)) and ferrous (reduced; Fe(II)) and readily forms complexes with oxygen, making this metal a central player in respiration and related redox processes. However, loose iron, not within heme or iron-sulfur cluster proteins, can be destructively redox-active, causing damage to almost all cellular components, killing both cells and organisms. This may explain why iron is so carefully handled by aerobic organisms. Iron uptake from the environment is carefully limited and carried out by specialized iron transport mechanisms. One reason that iron uptake is tightly controlled is that most organisms and cells cannot efficiently excrete excess iron. When even small amounts of intracellular free iron occur, most of it is safely stored in a non-redox-active form in ferritins. Within nucleated cells, iron is constantly being recycled from aged iron-rich organelles such as mitochondria and used for construction of new organelles. Much of this recycling occurs within the lysosome, an acidic digestive organelle. Because of this, most lysosomes contain relatively large amounts of redox-active iron and are therefore unusually susceptible to oxidant-mediated destabilization or rupture. In many cell types, iron transit through the lysosomal compartment can be remarkably brisk. However, conditions adversely affecting lysosomal iron handling (or oxidant stress) can contribute to a variety of acute and chronic diseases. These considerations make normal and abnormal lysosomal handling of iron central to the understanding and, perhaps, therapy of a wide range of diseases

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“…Recent evidence suggests that regular day-long periods of starvation may, by stimulating autophagy, help to "keep cells clean" and be beneficial and prolong life (Cuervo et al, 2005). …”

Section: The Role Of Lysosomes In Intracellular Iron Metabolismmentioning

confidence: 99%

The role of lysosomes in iron metabolism and recycling

Kurz

Eaton

Brunk

2011

The International Journal of Biochemistry & Cell Biology

Self Cite

175

134

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“…In addition, this phenomenon may reflect the lower function of cellular degradation system with advancing age. Cellular degradation system can remove cytoplasmic materials and organelles by lysosomal degradation (Ciechanover 2005;Wolf and Hilt 2004;Mizushima et al 2004;Cuervo et al 2005). The accumulation of lipofuscin in lysosome may slow down autophagocytosis and impair the degradation of mitochondria, leading to the accumulation of dysfunction of mitochondria in old workers.…”

Section: Mitochondrial Densitymentioning

confidence: 99%

Changes in mitochondrial energy utilization in young and old worker honeybees (Apis mellifera)

Chuang

Hsu

2012

AGE

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Trophocytes and fat cells in honeybees (Apis mellifera) have served as targets for cellular senescence studies, but mitochondrial energy utilization with advancing age in workers is unknown. In this study, mitochondrial energy utilization was evaluated in the trophocytes and fat cells of young and old workers reared in a field hive. The results showed that (1) mitochondrial density increased with advancing age; (2) mitochondrial membrane potential (ΔΨm), nicotinamide adenine dinucleotide oxidized form (NAD + ) concentration, adenosine triphosphate (ATP) concentration, and NAD + /nicotinamide adenine dinucleotide reduced form (NADH) ratio decreased with advancing age; and (3) the expression of NADH dehydrogenase 1 (ND1), ATP synthase, and voltage-dependent anion channel 1 (VDAC1) increased with advancing age, whereas ND1 and ATP synthase did not differ with advancing age after normalization to mitochondrial density and VDAC1. These results show that the trophocytes and fat cells of young workers have higher mitochondrial energy utilization efficiency than those of old workers and that aging results in a decline in mitochondrial energy utilization in the trophocytes and fat cells of worker honeybees.

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“…Autophagy is responsible for the degradation of most long-lived proteins and some organelles (Cuervo et al 2005). The amino acids, fatty acids, and carbohydrates produced by autophagy can be reused for biosynthesis or energy production (Lum et al 2005).…”

Section: Sa-β-gal and Lipofuscin Granulesmentioning

confidence: 99%

The use of honeybees reared in a thermostatic chamber for aging studies

Hsu

Chan

2011

AGE

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Honeybees (Apis mellifera) are an attractive model system for studying aging. However, the aging level of worker honeybees from the field hive is in dispute. To eliminate the influence of task performance and confirm the relationship between chronological age and aging, we reared newly emerged workers in a thermostat at 34°C throughout their lives. A survivorship curve was obtained, indicating that workers can be reared away from the field hive, and the only difference between these workers is age. To confirm that these workers can be used for aging studies, we assayed age-related molecules in the trophocytes and fat cells of young and old workers. Old workers expressed more senescence-associated β-galactosidase, lipofuscin granules, lipid peroxidation, and protein oxidation than young workers. Furthermore, cellular energy metabolism molecules were also assayed. Old workers exhibited less ATP concentration, β-oxidation, and microtubule-associated protein light chain 3 (LC3) than young workers. These results demonstrate that honeybees reared in a thermostatic chamber can be used for aging studies and cellular energy metabolism in the trophocytes and fat cells of workers changes with advancing age.

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Autophagy and Aging: The Importance of Maintaining "Clean" Cells

Cited by 740 publications

References 141 publications

The role of lysosomes in iron metabolism and recycling

The role of lysosomes in iron metabolism and recycling

Changes in mitochondrial energy utilization in young and old worker honeybees (Apis mellifera)

The use of honeybees reared in a thermostatic chamber for aging studies

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