Towards an understanding of the anti-aging mechanism of dietary restriction: A signal transduction theory of aging

Bergamini, Ettore; Gori, Zina

doi:10.1007/bf03324374

Cited by 23 publications

(9 citation statements)

References 7 publications

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“…132 Extensive evidence may now support this hypothesis, showing that caloric restriction prevents the accumulation of altered proteins in cytosol and membranes, 129 the increase in liver tissue dolichol, 6 and the accumulation of altered mtDNA. Caloric restriction preserves the juvenile function and regulation of macroautophagy.…”

Section: Restorative Efforts: a Multi-front Attack?mentioning

confidence: 95%

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

et al. 2005

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Previously published online as an Autophagy E-publication: http://www.landesbioscience.com/journals/autophagy/abstract.php?id=2017 KEY WORDS Review Autophagy and AgingThe Importance of Maintaining "Clean" Cells ABSTRACTA decrease in the turnover of cellular components and the intracellular accumulation of altered macromolecules and organelles are features common to all aged cells. Diminished autophagic activity plays a major role in these age-related manifestations. In this work we review the molecular defects responsible for the malfunctioning of two forms of autophagy, macroautophagy and chaperone-mediated autophagy, in old mammals, and highlight general and cell-type specific consequences of dysfunction of the autophagic system with age. Dietary caloric restriction and antilipolytic agents have been proven to efficiently stimulate autophagy in old rodents. These and other possible experimental restorative efforts are discussed.

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Section: Restorative Efforts: a Multi-front Attack?mentioning

confidence: 95%

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

et al. 2005

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“…Similar results (under less‐controlled conditions) had been obtained by our group 20 and explanation was that 40% CR rats are very hungry and consume all their given food in less than 6 hours after feeding (in other words, the feeding pattern of 40% CR rats resembles that of every‐other‐day ad libitum feeding (EOD) rats, which spend 24 hours of their time fed (during the day of feeding) and the next 24 hours in the state of fasting. These observations led two of us to propose a different hypothesis, based on the well‐known stimulatory effect of fasting and lower insulin levels on autophagy, 23 a cell‐repair mechanism which is essential for keeping cells “clean” ( 1). Additional support for this hypothesis came by discovery that loss‐of‐function mutations in genes coding for components of the cellular insulin‐like signaling pathway markedly increase the longevity of worms, and that the target‐of‐rapamycin (TOR) pathway, which regulates protein synthesis and autophagic degradation rates, may be involved 24 …”

Section: The Anti‐aging Mechanism Of Calorie Restrictionmentioning

confidence: 99%

The Role of Autophagy in Aging

Bergamini¹,

Cavallini²,

Donati³

et al. 2007

Annals of the New York Academy of Sciences

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123

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Aging denotes a postmaturational deterioration of cells and organisms with the passage of time, an increased vulnerability to challenges and prevalence of age-associated diseases, and a decreased ability to survive. Causes of this deterioration may be found in an enhanced production of reactive oxygen species (ROS) and oxidative damage and incomplete "housekeeping." Caloric restriction is the most robust anti-aging intervention known so far. Similar beneficial effects on median and maximum life span were obtained by feeding animals a 40%-reduced diet or by every-other-day ad libitum feeding. In both instances, animals are forced to spend a great part of their time in a state of fasting and activated autophagy. Autophagy is a highly conserved process in eukaryotes, in which the cytoplasm, including excess or aberrant organelles, is sequestered into double-membrane vesicles and delivered to the lysosome/vacuole, for breakdown and eventual recycling of the resulting macromolecules. This process has an essential role in adaptation to fasting and changing environmental conditions, cellular remodeling during development, and accumulation of altered ROS-hypergenerating organelles in older cells. Several pieces of evidence show that autophagy is involved in aging and is an essential part of the anti-aging mechanism of caloric restriction. As an application, intensification of autophagy by the administration of an antilipolytic drug rescued older cells from accumulation of altered mtDNA in less than 6 hours. It is concluded that the pharmacologic intensification of autophagy (PISA treatment) has anti-aging effects and might prove to be a big step toward retardation of aging and prevention of age-associated diseases in humans.

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“…These results confirm that the transfer of dolichol from and to tissues and/or from the peripheral tissues to the liver via circulation is negligible (Elmberger et al 1987); and provide evidence that accumulation of dolichol in older tissues is a primary effect of aging, may be the consequence of an alteration of dolichol metabolism in those tissues or a defence attempt against an increased an increased free radical attack. Indeed it was hypothesized that the age-related changes in dolichol levels might reflect an aging-related derangement of free radical metabolism in cell membranes (Bergamini et al 2004), possibly associated with a larger peroxidation of membrane proteins and an alteration in transmembrane signalling (Cavallini et al 2001;Bergamini and Gori 1995;and unpublished). If this is the case, the age-associated cell-membrane defect(s) in free-radical metabolism should be resistant to organ transplantation.…”

Section: Discussionmentioning

confidence: 96%

Changes in dolichol and pentosidine levels in the age-mismatched heterotopically transplanted rat heart

et al. 2004

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To address some basic questions about primary and secondary events in the process of aging in different cell and tissue types, we studied changes in the levels of biomarkers of the aging cells (dolichol) and connective tissue (pentosidine) in the heart of older (22-month-old) Lewis rats heterotopically transplanted in younger (3-month-old) syngenic recipients. Results showed that age-mismatched transplantation did not alter the age-related accumulation of dolichol and significantly reduced the accumulation of pentosidine in cardiac tissue. It is concluded that aging of heart muscle and connective tissues is controlled by two independent clocks; that accumulation of dolichol in older tissues may be a primary consequence of the process of aging, whereas the accumulation of pentosidine may be secondary, perhaps to changes in circulating cells endowed with advanced glycation end products-specific receptors; in the perspective of organ transplantation, the environment of a younger host may positively interact with the graft and rejuvenate its collagen.

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Towards an understanding of the anti-aging mechanism of dietary restriction: A signal transduction theory of aging

Cited by 23 publications

References 7 publications

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

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

The Role of Autophagy in Aging

Changes in dolichol and pentosidine levels in the age-mismatched heterotopically transplanted rat heart

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