List of Legitimate Studies, Published in Reputable Scientific Journals by Established Researchers, That Use the Term "Anti-Aging" to Describe the Postponement of Chronic Diseases, Frailty, and Death

To make them more conspicuous, terms like 'anti-aging' in the titles of these publications have been highlighted in ALL CAPS:

Cavallini G, Donati A, Gori Z, Pollera M, Bergamini E.  The protection of rat liver autophagic proteolysis from the age-related decline co-varies with the duration of ANTI-AGEING food restriction.  Exp Gerontol  2001 36(3):497-506
Restricting caloric intake (CR) well below that of ad libitum (AL) fed animals retards and/or delays many characteristics of ageing and the occurrence and progression of age-associated diseases, efficacy depending on duration. The hypothesis that the anti-ageing effect of CR might involve stimulation of the cell-repair mechanism autophagy was tested. The effects of ageing and duration of anti-ageing CR on liver autophagic proteolysis (AP) were explored in male AL Sprague-Dawley rats aged 2-, 6-, 12- and 24-months; and 24-month-old rats on a CR diet initiated at 2-, 6- and 12-month of age or initiated at age 2-months and interrupted at age 18 months. The age-related changes in the regulation of AP were studied by monitoring the rate of valine release in the incubation medium from isolated liver cells by an HPLC procedure. Results show that the maximum attainable rate and the regulation of AP decline with increasing age; that changes are prevented by anti-ageing CR initiated at young age, that the protective effects of CR change with the duration of diet. It is concluded that the data are compatible with the hypothesis that AP and improved membrane maintenance might be involved in the antiageing mechanism of CR.

Hipkiss AR.  Carnosine, a protective, ANTI-AGEING peptide? Int J Biochem Cell Biol 1998 30(8):863-8
Carnosine (beta-alanyl-L-histidine) has protective functions additional to anti-oxidant and free-radical scavenging roles. It extends cultured human fibroblast life-span, kills transformed cells, protects cells against aldehydes and an amyloid peptide fragment and inhibits, in vitro, protein glycation (formation of cross-links, carbonyl groups and AGEs) and DNA/protein cross-linking. Carnosine is an aldehyde scavenger, a likely lipofuscin (age pigment) precursor and possible modulator of diabetic complications, atherosclerosis and Alzheimer's disease.

Hipkiss AR, Brownson C.  A possible new role for the ANTI-AGEING peptide carnosine.  Cell Mol Life Sci 2000 57(5):747-53
The naturally occurring dipeptide carnosine (beta-alanyl-L-histidine) is found in surprisingly large amounts in long-lived tissues and can delay ageing in cultured human fibroblasts. Carnosine has been regarded largely as an anti-oxidant and free radical scavenger. More recently, an anti-glycating potential has been discovered whereby carnosine can react with low-molecular-weight compounds that bear carbonyl groups (aldehydes and ketones). Carbonyl groups, arising mostly from the attack of reactive oxygen species and low-molecular-weight aldehydes and ketones, accumulate on proteins during ageing. Here we propose, with supporting evidence, that carnosine can react with protein carbonyl groups to produce protein-carbonyl-carnosine adducts ('carnosinylated' proteins). The various possible cellular fates of the carnosinylated proteins are discussed. These proposals may help explain anti-ageing actions of carnosine and its presence in non-mitotic cells of long-lived mammals.

Hipkiss AR, Brownson C.  Carnosine reacts with protein carbonyl groups: another possible role for the ANTI-AGEING peptide? Biogerontology 2000;1(3):217-23
Carnosine (beta-alanyl-L-histidine) can delay senescence and provoke cellular rejuvenation in cultured human fibroblasts. The mechanisms by which such a simple molecule induces these effects is not known despite carnosine's well documented anti-oxidant and oxygen free-radical scavenging activities. Carbonyl groups are generated on proteins post-synthetically by the action of reactive oxygen species and glycating agents and their accumulation is a major biochemical manifestation of ageing. We suggest that, in addition to the prophylactic actions of carnosine, it may also directly participate in the inactivation/disposal of aged proteins possibly by direct reaction with the carbonyl groups on proteins. The possible fates of these 'carnosinylated' proteins including the formation of inert lipofuscin, proteolysis via the proteasome system and exocytosis following interaction with receptors are also discussed. The proposal may point to a hitherto unrecognised mechanism by which cells/organisms normally defend themselves against protein carbonyls.

Hipkiss AR, Brownson C, Carrier MJ.  Carnosine, the ANTI-AGEING, anti-oxidant dipeptide, may react with protein carbonyl groups. Mech Ageing Dev 2001 122(13):1431-45
Carnosine (beta-alanyl-L-histidine) is a physiological dipeptide which can delay ageing and rejuvenate senescent cultured human fibroblasts. Carnosine's anti-oxidant, free radical- and metal ion-scavenging activities cannot adequately explain these effects. Previous studies showed that carnosine reacts with small carbonyl compounds (aldehydes and ketones) and protects macromolecules against their cross-linking actions. Ageing is associated with accumulation of carbonyl groups on proteins. We consider here whether carnosine reacts with protein carbonyl groups. Our evidence indicates that carnosine can react non-enzymically with protein carbonyl groups, a process termed 'carnosinylation'. We propose that similar reactions could occur in cultured fibroblasts and in vivo. A preliminary experiment suggesting that carnosine is effective in vivo is presented; it suppressed diabetes-associated increase in blood pressure in fructose-fed rats, an observation consistent with carnosine's anti-glycating actions. We speculate that: (i) carnosine's apparent anti-ageing actions result, partly, from its ability to react with carbonyl groups on glycated/oxidised proteins and other molecules; (ii) this reaction, termed 'carnosinylation,' inhibits cross-linking of glycoxidised proteins to normal macromolecules; and (iii) carnosinylation could affect the fate of glycoxidised polypeptides.

Knook DL. ANTIAGING strategies.  Ann. N. Y. Acad. Sci. 1992 663:372-5.
No abstract available at this time.

Lane MA, Baer DJ, Rumpler WV, Weindruch R, Ingram DK, Tilmont EM, Cutler RG, Roth GS  Calorie restriction lowers body temperature in rhesus monkeys, consistent with a postulated ANTI-AGING mechanism in rodents. Proceedings of the National Academy of Sciences of the United States of America 1996 93 (9): 4159-4164
Many studies of caloric restriction (CR) in rodents and lower animals indicate that this nutritional manipulation retards aging processes, as evidenced by increased longevity, reduced pathology, and maintenance of physiological function in a more youthful state. The anti-aging effects of CR are believed to relate, at least in part, to changes in energy metabolism. We are attempting to determine whether similar effects occur in response to CR in nonhuman primates. Core (rectal) body temperature decreased progressively with age from 2 to 30 years in rhesus monkeys fed ad lib (controls) and is reduced by approximate to 0.5 degrees C in age-matched monkeys subjected to 6 years of a 30% reduction in caloric intake. A short-term (1 month) 30% restriction of 2.5-year-old monkeys lowered subcutaneous body temperature by 1.0 degrees C. Indirect calorimetry showed that 24-hr energy expenditure was reduced by approximately 24% during short-term CR. The temporal association between reduced body temperature and energy expenditure suggests that reductions in body temperature relate to the induction of an energy conservation mechanism during CR. These reductions in body temperature and energy expenditure are consistent with findings in rodent studies in which aging rate was retarded by CR, now strengthening the possibility that CR may exert beneficial effects in primates analogous to those observed in rodents.

Masoro EJ.  Potential role of the modulation of fuel use in the ANTIAGING action of dietary restriction. Ann N Y Acad Sci 1992 663:403-11
No abstract available at this time

Masoro EJ. ANTIAGING action of caloric restriction: endocrine and metabolic aspects. Obes Res 1995 3 Suppl 2:241s-247s
Restricting the energy intake of mice and rats slows the rate of actuarial aging, delays or prevents most age-associated disease processes, and maintains physiological processes in a youthful state at advanced ages. This manipulation is effective when initiated in young animals or in adult life. Although body fat is decreased by this reduction in energy intake, the reduction in body fat is not causally related to the antiaging action. Nor does this reduction in energy intake slow the aging processes by decreasing the metabolic rate, but it may do so by altering the characteristics of fuel use. Another possible mechanism underlying the antiaging action is the general protection restriction of energy intake provides against harmful agents, an action which may be the result of an alteration in adrenal glucocorticoid physiology.

Masoro EJ. Possible mechanisms underlying the ANTIAGING actions of caloric restriction. Toxicol Pathol 1996 24(6):738-41
Restricting the food intake of mice and rats to well below that of ad libitum-fed animals markedly slows the aging processes. This action is reflected in an increase in longevity, a decrease in the age-associated increase in age-specific mortality rate, the maintenance of the physiological processes in a youthful state even at advanced ages, and the delaying of the onset or slowing of the progression or both of most age-associated diseases. The dietary factor responsible is the reduction in energy (caloric) intake. Many hypotheses have been proposed regarding mechanisms underlying this antiaging action. Hypotheses relating the antiaging action to the retardation of growth and development, the reduction of adipose mass, and the reduction of metabolic rate have been found to be wanting. Two of the proposed hypotheses have some evidence in their support. One involves the altered metabolic characteristics of glucose fuel use and of oxidative metabolism. The other relates to the enhanced ability of the rodents restricted in food intake to cope with challenges, which in turn has been linked to the glucocorticoid system and to the heat-shock protein system.

Masoro EJ. Hormesis and the ANTIAGING action of dietary restriction. Exp Gerontol 1998 33(1-2):61-6
Hormesis refers to the often encountered phenomenon of a beneficial biological action from a factor or agent that is generally viewed as detrimental. Beneficial actions that have been observed include life span extension. It is proposed that life span extension in rodents by dietary restriction is an example of hormesis and that sustained moderate hyperadrenocorticism underlies this life prolongation. Evidence supporting this concept is presented. The possibility is also suggested that whenever hormesis leads to an extension of mammalian life span, it is likely that moderate hyperadrenocorticism plays a major role.

Masoro EJ, Austad SN. The evolution of the ANTIAGING action of dietary restriction: a hypothesis. J Gerontol A Biol Sci Med Sci 1996 51(6):B387-91
Reducing the intake of dietary energy by laboratory rodents to well below that of animals allowed to eat ad libitum slows the rate of aging. This phenomenon, which is robust and reproducible, is known as the antiaging action of dietary restriction (DR). We hypothesize that this DR response arose because of its evolutionary advantage with respect to survival during periods of unpredictable, short-term food shortage. In our evolutionary scenario, food shortage led to an adaptive redirection of resources away from reproduction toward somatic maintenance via an enhanced heat shock protein response in invertebrates. In vertebrates, an additional involvement of the hypothalamic-adenohypophyseal-adrenal glucocorticoid system was necessitated to protect against excessive systemic defense responses. We suggest several general implications of our hypothesis.

Meites J.  ANTI-AGEING interventions and their neuroendocrine aspects in mammals. J. Reprod. Fertil., Suppl 1993;46:1-9.
A number of interventions for delaying or reversing declines in body functions due to ageing are critically reviewed here, including their relation to neuroendocrine function. Diets severely deficient in calories retard the ageing of body tissues, inhibit the development of disease and tumours, and significantly prolong the lifespan of rats and mice. Such diets also decrease hormone secretion, reduce the metabolism of the whole body, and lower gene expression. Administration of hormones, thymic peptides and other immune factors, and appropriate drugs can improve declining immune function in old rats and mice, thereby increasing resistance to infection, autoimmune disease and tumours. In old rats, correction of faults that develop in the neuroendocrine system with age--particularly in the hypothalamus--can restore oestrous cycles, increase the secretion of growth hormone, increase protein synthesis, inhibit development of disease and tumours, and prolong life. Antioxidants administered to rats and mice in an attempt to reduce damage to cells caused by free radicals, do not significantly retard ageing or prolong the lifespan of these animals. Regular, moderate exercise in elderly humans decreases incidence of heart disease, improves lung function, reduces bone loss, and produces other beneficial effects. Suitable drugs that will improve memory function in elderly humans remain to be developed, although a few have produced small improvements albeit with undesirable side effects. Overall, the neuroendocrine and immune approaches offer the best prospects for delaying and reversing declines in body functions due to ageing.

Moriguchi T, Saito H, Nishiyama N.  ANTI-AGEING effect of aged garlic extract in the inbred brain atrophy mouse model.  Clin. Exp. Pharmacol. Physiol. 1997 24(3-4):235-42
   1. The effects of chronically administered aged garlic extract (AGE) on the age-related changes in a novel strain of senescence accelerated mouse (SAM) characterized by age-related brain atrophy (SAMP10) were investigated. 2. A solid diet containing 2% (w/w) AGE was given to SAM from 2 months of age. 3. The grading score of senescence in SAMP10 at 10 months of age was significantly higher than that of SAMR1, a reference strain for SAMP10. 4. Administration of AGE prevented the increase in the grading score of SAMP10 and SAMR1. 5. In behavioural evaluation, AGE improved learning and memory deficits of SAMP10 in both the passive and conditioned avoidance tests as well as the spatial memory test. 6. Treatment with AGE in SAMP10 prevented the decrease in brain weight and the atrophic changes in frontal brain at 12 months of age. 7. These results raise the possibility that AGE prevents physiological ageing and may be beneficial for age-related cognitive disorders in humans.

Novelli M, Masiello P, Bombara M, Bergamini E. Protein glycation in the aging male Sprague-Dawley rat: effects of ANTIAGING diet restrictions. J Gerontol A Biol Sci Med Sci 1998 53(2):B94-101
Protein glycation and accumulation of advanced glycosylated end-products (AGEs) are supposed to play an important role in the process of aging. Dietary restriction increases life span and delays the onset of most age-associated diseases. Age-dependent changes in glucose homeostasis and glycated plasma proteins and hemoglobin were determined, and AGEs formation was measured as fluorescence in skin and aortic collagens in male Sprague-Dawley rats fed ad libitum or subjected to every-other-day feeding or 40% food restriction. In aging control rats, skin and aortic collagen-linked fluorescence increased with a similar exponential curve (aortic value being always higher), whereas glycated plasma protein and hemoglobin decreased slightly. Dietary restrictions decreased glycated plasma proteins and fluorescent products in skin collagen of younger but not older rats, and did not affect glycated hemoglobin or aortic collagen fluorescence. In conclusion, our data indicate that age-related changes in glucose homeostasis do not play a substantial role in aging; and collagen-linked fluorescence increases significantly during aging, but it may not be sensitive to dietary intervention

Rattan SI. The nature of gerontogenes and vitagenes. ANTIAGING effects of repeated heat shock on human fibroblasts. Ann N Y Acad Sci 1998 854:54-60
Our survival and the physical quality of life depends upon an efficient functioning of various maintenance and repair processes. This complex network of the so-called longevity assurance processes is composed of several genes, termed vitagenes. The homeodynamic property of living systems is a function of such a vitagene network. Because aging is characterized by the failure of homeodynamics, a decreased efficiency and accuracy of the vitagene network can transmutate it into a gerontogene network. It is not clear how various components of the vitagene network operate and influence each other in a concordant or a discordant manner. Experimental strategies through which this transmutation of vitagenes into virtual gerontogenes may be elucidated include induction of molecular damage, antisense intervention, and genetic screening for varied efficiencies of the members of the vitagene family. A reversal of this approach by maintaining or recovering the activity of vitagenes will lead to a delay of aging, a decreased occurrence of age-related diseases, and a prolongation of a healthy life span.

Shimokawa I, Higami Y.   A role for leptin in the ANTIAGING action of dietary restriction: a hypothesis.  Aging (Milano) 1999 11(6):380-2.
A neuroendocrine signal may play an important role in the antiaging action of dietary restriction (DR). Recent studies have suggested that falling leptin levels by starvation activate the hypothalamic-pituitary-adrenal axis, and suppress gonadal, somatotropic, and thyroid axes as a response for adaptation. Accumulated evidence indicates that similar hormonal changes also occur in DR rodents. In this article, we advance that a reduction in plasma leptin levels in DR rodents might be a critical neuroendocrine modulator in the antiaging action of dietary restriction.

Svendsen L, Rattan SI, Clark BF. Testing garlic for possible ANTI-AGING effects on long-term growth characteristics, morphology and macromolecular synthesis of human fibroblasts in culture. Ethnopharmacol 1994 43(2):125-33
The beneficial effects claimed for the use of garlic as a nutritional supplement include detoxification, antioxidation, antifungal activity, antibacterial activity, tumour suppression and, possibly, anti-ageing and rejuvenating effects. We have used the Hayflick system of cellular ageing in culture in order to test garlic for its anti-ageing effects on long-term growth characteristics, morphology and macromolecular synthesis of human skin fibroblasts. Our results show that an addition of garlic extract into the normal cell culture medium can support serial subculturing for over more than 55 population doublings in 475 days, and that this treatment has some youth-preserving, anti-ageing and beneficial effects on human fibroblasts in terms of maximum proliferative capacity and morphological characteristics. In comparison, similar or lesser doses of garlic extracts are growth inhibitory for cancerous cells that could not be grown over longer periods in the presence of garlic. To our knowledge, this is the first report of the effects of garlic on the long-term growth characteristics and macromolecular synthesis of normal human skin cells, the results of which have applications for both anti-ageing and anti-cancer research.

Yu BP  Approaches to ANTI-AGING intervention: the promises and the uncertainties.  Mech Ageing Dev 1999 111 (2-3): 73-87
Humans have long sought the elixir to long life. Today, although advances in our understanding of the aging process have given gerontologists new insights in potential anti-aging interventions, public demand for these interventions is outpacing our current knowledge. My presentation begins with a brief historical background that outlines some of the past and present approaches to anti-aging interventions. Using the dietary restriction paradigm as a prototype, discussions center on a three-pathway model that provides the bases to design effective interventions: (1) retardation of biological aging, (2) suppression of age-related disease, and (3) modulation of cross talk between (1) and (2). One other concept useful for discussion in relation to interventions is the enhancement of an organism's resistance to deter vulnerability to aging and disease. These models are best used to explain the efficacy of currently popular interventions such as antioxidant supplementation and hormone therapies. This presentation further highlights the promises that antioxidant supplements hold in warding off oxidative damage as well as their inherent problems and biological limitations. Also discussed here are the promises and uncertainties of anti-aging interventions by genetic manipulation, as seen in animal model studies, and prophylactic treatments targeted against disease, such as hormonal approaches using estrogen and DHEA, as well as other intervening measures.

Van Remmen H, Guo Z, Richardson A. The ANTI-AGING action of dietary restriction. Novartis Found Symp 2001;235:221-30
Over 60 years ago, McCay's laboratory showed that dietary or calorie-restriction dramatically increased the lifespan of rats. Since then, numerous laboratories with a variety of strains of rats and mice have confirmed this initial observation and have shown that reducing calorie intake (without malnutrition) significantly increases both the mean and maximum survival of rodents. Currently, dietary restriction is the only experimental manipulation that has been shown to retard ageing of mammals. Although mechanism whereby dietary restriction retards ageing is currently unknown, much of the emerging data suggest that the calorie-restricted rodents live longer and age more slowly because they are more resistant to stress and have an enhanced ability to protect cells against damaging agents.