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Autophagy is a process that sequesters and degrades altered organelles and macromolecular cytoplasmic constituents for cellular restructuring and repair, and as a source of nutrients for metabolic use in early starvation it may be involved in anti-aging mechanisms of caloric restriction. The effects of 40% daily dietary restriction (DR) and intermittent feeding (EOD) on the age-related changes in the endocrine regulation of autophagic proteolysis were studied by monitoring the rate of valine release from isolated rat liver cells. Results show that in ad libitum-fed rats sensitivity of autophagy to glucagon and insulin declines by one order of magnitude in older rats. Both DR and EOD maintain the sensitivity to glucagon at juvenile levels, whereas only EOD can fully maintain response to insulin. It is concluded that changes in the sensitivity to glucagon may have a role in the aging process. [ABSTRACT FROM AUTHOR]

Criteria for defining biomarkers have been suggested. Accumulation of dolichol in tissues of older animals meets the following criteria: (a) levels of dolichol exhibit a quantitative correlation with age in all tissues and are not altered by several age-dependent diseases in the same direction as that of aging; (b) accumulation is not secondary to metabolic changes of aging and is altered appropriately by factors that modulate the aging rate like caloric restriction and physical exercise; (c) biomarker is applicable to different tissues across mammalian species, including humans, and to trisomy 21 and its hypothalamic digoxin-mediated model. Reliable changes in tissue dolichol levels are seen in relatively short intervals of time compared to over a life span, and levels can be tested on a small amount of tissue without causing death of the animal. In this article, we show applications to the study of host-graft interaction and detection of gender-related differences in biological age, and we discuss mechanism(s) of accumulation. [ABSTRACT FROM AUTHOR]

Autophagy is a process that sequesters and degrades organelles and macromolecular constituents of cytoplasm for cellular restructuring and repair and as a source of nutrients for metabolic use in early starvation. The effects of two antiaging dietary regimens (initiated in rats at the age of 2 months), namely, 40% dietary restriction (DR) and every-other-day ad-libitum feeding, that exhibited different effects on metabolism and similar effects on longevity on the age-related changes in the regulation of autophagic proteolysis were studied by monitoring the rate of valine release in the incubation medium from isolated liver cells of male albino Sprague-Dawley rats aged 2, 6, 12, 18, 24, and 27 months. (The liver cells were incubated in vitro with added amino acids and 10(-7) M insulin or glucagon.) Age-matched male albino Sprague-Dawley rats fed ad libitum served as a control. Results show that in ad-libitum-fed rats, after a transient increase by age 6 months, autophagic proteolysis and regulation by amino acid exhibit a dramatic age-related decline, and that the age-related changes are prevented by dietary antiaging intervention. A comparison shows that the protective effects of DR and every-other-day ad-libitum feeding are partially different in 24-month-old rats (but the beneficial effects of the two diets on regulation of autophagic proteolysis are always similar). With regard to endocrine regulation, results confirm that the liver cell response to glucagon (but not to insulin) declines with increasing age, and they show that antiaging DRs significantly improve the effects of glucagon (and have no effect on the response to insulin). The interactions of age by diet, glucagon (and in older rats, insulin), and amino acids are significant. It is concluded that DR significantly improves the susceptibility of liver cells to lysosomal degradation, and it prevents decline with increasing age. It is suggested that improved liver autophagy and lysosomal degradation might be part of the antiaging mechanisms of DR. [ABSTRACT FROM AUTHOR]

During intervals between meals, autophagy is a major source of nutrients and may remove damaged organelles and membranes. Age-related changes in the regulation of autophagic proteolysis were studied by monitoring the rate of valine release from liver cells of 2-, 6-, 12-, 18-, and 24-month-old male Sprague-Dawley rats fed ad libitum, and incubated in vitro with added amino acids and 10(-7) M of insulin or glucagon. The maximum rate of proteolysis and its maximum inhibition by amino acids were reached at 6 months and declined thereafter. In contrast, the rate of protein degradation in the presence of high concentrations of amino acids was not affected by aging. The inhibitor effect of insulin was additive to that of amino acids and was not altered significantly by age. The conclusion is that altered regulation of autophagic proteolysis decreases susceptibility of older cells to lysosomal degradation, and it may lead to the accumulation of altered organelles and membranes. [ABSTRACT FROM AUTHOR]

Comments on the article 'Is There an Antiaging Medicine?,' which was published in the 2002 issue of 'The Journals of Gerontology.' Theme of the article; Background on autophagy; Description of the treatment developed by the Pharmacological Intensification of Suppression of Aging.