Interdisciplinary topics in gerontology最新文献_第5页

Senescent cells and their secretory phenotype as targets for cancer therapy. 衰老细胞及其分泌表型作为癌症治疗的靶点。

Interdisciplinary topics in gerontology Pub Date : 2013-01-01 Epub Date: 2013-01-17 DOI: 10.1159/000343572

Michael C Velarde, Marco Demaria, Judith Campisi

{"title":"Senescent cells and their secretory phenotype as targets for cancer therapy.","authors":"Michael C Velarde, Marco Demaria, Judith Campisi","doi":"10.1159/000343572","DOIUrl":"10.1159/000343572","url":null,"abstract":"Cancer is a devastating disease that increases exponentially with age. Cancer arises from cells that proliferate in an unregulated manner, an attribute that is countered by cellular senescence. Cellular senescence is a potent tumor-suppressive process that halts the proliferation, essentially irreversibly, of cells at risk for malignant transformation. A number of anti-cancer drugs have emerged that induce tumor cells to undergo cellular senescence. However, although a senescence response can halt the proliferation of cancer cells, the presence of senescent cells in tissues has been associated with age-related diseases, including, ironically, late-life cancer. Thus, anti-cancer therapies that can induce senescence might also drive aging phenotypes and age-related pathology. The deleterious effects of senescent cells most likely derive from their senescence-associated secretory phenotype or SASP. The SASP entails the secretion of numerous inflammatory cytokines, growth factors and proteases that can render the tissue microenvironment favorable for tumor growth. Here, we discuss the beneficial and detrimental effects of inducing cellular senescence, and propose strategies for targeting senescent cells as a means to fight cancer.","PeriodicalId":87437,"journal":{"name":"Interdisciplinary topics in gerontology","volume":"38 ","pages":"17-27"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4167737/pdf/nihms-628034.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31315170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exercise as a calorie restriction mimetic: implications for improving healthy aging and longevity. 运动作为一种卡路里限制模拟:促进健康老龄化和长寿的意义。

Interdisciplinary topics in gerontology Pub Date : 2010-01-01 Epub Date: 2010-08-10 DOI: 10.1159/000320000

Derek M Huffman

{"title":"Exercise as a calorie restriction mimetic: implications for improving healthy aging and longevity.","authors":"Derek M Huffman","doi":"10.1159/000320000","DOIUrl":"https://doi.org/10.1159/000320000","url":null,"abstract":"Calorie restriction (CR) is the only paradigm that has consistently increased lifespan in a wide variety of model organisms. Many hypotheses have been proposed as the underlying mechanism, including a reduction in body size and adiposity, which is commonly observed in calorie-restricted animals. This has led to investigations as to whether similar changes in body composition produced by increasing energy expenditure via exercise can replace or enhance the benefits of reducing energy intake. The goal of this chapter is to review and discuss the evidence regarding exercise as a CR mimetic for healthy aging and longevity. In rodents, the data clearly show that exercise, regardless of body weight changes, can improve health and survival, but unlike CR, fails to extend lifespan. In humans, short-term weight loss studies show that exercise and CR produce similar improvements in disease risk factors and biomarkers of aging, while some parameters clearly benefit more with exercise. Epidemiologic evidence in humans supports exercise as a strategy to reduce the risk of morbidity and mortality, but not to extend lifespan. It is unknown whether CR can extend human lifespan, but the metabolic profile of humans engaged in long-term CR shares many similarities with calorie restricted rodents and nonhuman primates. In conclusion, like CR, exercise can limit weight gain and adiposity, but only CR can extend lifespan. Therefore, in rodents, the ability of CR to slow aging is apparently more dependent on decreasing nutrient flux, rather than changes in energy balance and body composition.","PeriodicalId":87437,"journal":{"name":"Interdisciplinary topics in gerontology","volume":"37 ","pages":"157-74"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000320000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29185136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 25

Central control of food intake in aging. 衰老过程中食物摄入的中枢控制。

Interdisciplinary topics in gerontology Pub Date : 2010-01-01 Epub Date: 2010-08-10 DOI: 10.1159/000319993

Zbigniew Kmiec

{"title":"Central control of food intake in aging.","authors":"Zbigniew Kmiec","doi":"10.1159/000319993","DOIUrl":"https://doi.org/10.1159/000319993","url":null,"abstract":"Energy homeostasis and fuel metabolism undergo significant modifications in the course of aging. This presents in elderly subjects either as increased body mass and glucose intolerance - which may lead to obesity and type 2 diabetes - or loss of appetite, which may also seriously compromise health. The hypothalamic expression of neuropeptide Y (NPY), the most potent orexigen, and its receptors, was highly suppressed in old rats. Moreover, induction of the NPY-dependent responses was severely blunted in old animals. Similar reductions, although of a lower magnitude, were reported for other hypothalamic orexigens, A and orexins. Orexigenic activity of ghrelin, the only peripheral orexigen, was clearly suppressed in old humans and rats. However, aging did not alter hypothalamic expression of key anorexigens, alpha-MSH and CART. Age-related decrease of central anorexigenic action of leptin was likely caused by the impaired leptin signal transduction. Thus, aging in rodents is associated with the general down-regulation of orexigenic hypothalamic pep-tides - and unchanged expression of anorexigenic hypothalamic peptides - which may lead to weight loss at the end of life. If similar changes at the level of CNS underlie the 'anorexia of aging' observed in some elderly, therapeutic interventions at this regulatory level may be possible in the future.","PeriodicalId":87437,"journal":{"name":"Interdisciplinary topics in gerontology","volume":"37 ","pages":"37-50"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000319993","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29185129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

Obesity paradox during aging. 衰老过程中的肥胖悖论。

Interdisciplinary topics in gerontology Pub Date : 2010-01-01 Epub Date: 2010-08-10 DOI: 10.1159/000319992

Ian M Chapman

{"title":"Obesity paradox during aging.","authors":"Ian M Chapman","doi":"10.1159/000319992","DOIUrl":"https://doi.org/10.1159/000319992","url":null,"abstract":"Although obesity in young people is a risk factor for morbidity and mortality, the effect of obesity in the elderly is much more complex. For example, the body weight associated with maximal survival increases with increasing age. Even more striking is the 'obesity paradox' in the elderly, in which overweight is associated with increased risk for cardiovascular disease but decreased mortality from these diseases. Thus, although intentional weight loss by obese older people is probably safe, and likely to be beneficial if they have obesity-related morbidities, caution should be exercised in recommending weight loss to overweight older people on the basis of body weight alone. Methods of achieving weight loss in older adults are the same as in younger adults. Weight loss diets should be combined with an exercise program, if possible, to preserve muscle mass, as dieting results in loss of muscle as well as fat, and older people have reduced skeletal muscle mass compared to younger adults. Weight-loss drugs have not been extensively studied in older people and there is the potential for drug side effects and interactions. Weight loss surgery appears to be safe and effective, although it probably produces less weight loss than in younger adults. Little is yet known about the outcomes of such surgery in people over 65 years.","PeriodicalId":87437,"journal":{"name":"Interdisciplinary topics in gerontology","volume":"37 ","pages":"20-36"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000319992","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29183051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 101

Changes in food intake and its relationship to weight loss during advanced age. 老年时食物摄入量的变化及其与体重减轻的关系。

Interdisciplinary topics in gerontology Pub Date : 2010-01-01 Epub Date: 2010-08-10 DOI: 10.1159/000319994

Roger B McDonald, Rodney C Ruhe

{"title":"Changes in food intake and its relationship to weight loss during advanced age.","authors":"Roger B McDonald, Rodney C Ruhe","doi":"10.1159/000319994","DOIUrl":"https://doi.org/10.1159/000319994","url":null,"abstract":"The results of extensive human and animal studies suggest that declining food intake and body weight observed in the later stages of life may be part of the normal progression of physiological decline observed during aging. Proposed etiologies cover a wide range of biological and psychological conditions. Studies in humans suggest an imbalance in homeostatic mechanisms governing hunger and satiety. That is, while older vs. younger individuals retain a similar drive (hunger) to eat, satiety occurs sooner during a meal in aged people and leads to an overall decrease in daily food intake. Age-related weight loss and a reduction in food intake have also been observed in laboratory animals. Alterations in neurochemical control of energy balance, especially as they relate to long-term regulation of food intake, have received much attention in recent years as the likely mechanism underlying age-related spontaneous weight loss. Age-related changes to neuroendocrine factors such as neuropeptide Y, GABA, CCK, leptin, and insulin have been linked to spontaneous weight loss observed during late life. This brief review provides an update on putative mechanisms underlying the dysregulation of feeding during advanced age that result in body weight loss.","PeriodicalId":87437,"journal":{"name":"Interdisciplinary topics in gerontology","volume":"37 ","pages":"51-63"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000319994","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29185130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Sarcopenia: prevalence, mechanisms, and functional consequences. 肌肉减少症:流行、机制和功能后果。

Interdisciplinary topics in gerontology Pub Date : 2010-01-01 Epub Date: 2010-08-10 DOI: 10.1159/000319997

Michael J Berger, Timothy J Doherty

引用次数: 166

New haystacks reveal new needles: using Caenorhabditis elegans to identify novel targets for ameliorating body composition changes during human aging. 新的干草堆揭示新的针头:使用秀丽隐杆线虫来确定改善人类衰老过程中身体成分变化的新靶点。

Interdisciplinary topics in gerontology Pub Date : 2010-01-01 Epub Date: 2010-08-10 DOI: 10.1159/000319996

Catherine A Wolkow

{"title":"New haystacks reveal new needles: using Caenorhabditis elegans to identify novel targets for ameliorating body composition changes during human aging.","authors":"Catherine A Wolkow","doi":"10.1159/000319996","DOIUrl":"https://doi.org/10.1159/000319996","url":null,"abstract":"Dramatic changes in body composition accompany aging in humans, particularly with respect to adiposity and the musculature. People accumulate fat as they age and lose muscle mass and strength. Caenorhabditis elegans nematodes are small, hermaphroditic soil nematodes that offer a flexible model for studying genetic pathways regulating body composition in humans. While there are significant physiological differences between worms and people, many of the genetic pathways relevant to human lipid and muscle homeostasis are present in worms. Initial studies indicate that adiposity increases in C. elegans during aging, as occurs in humans. Furthermore, substantial evidence demonstrates age-related loss of muscle mass in worms. Possible mechanisms for these changes in C. elegans are presented. Recent studies have highlighted neuroendocrine and environmental signals regulating C. elegans fat metabolism. Potential dysfunction of these pathways during aging could affect overall fat accumulation. By contrast, muscle decline in aging worms results from accumulated damage and 'wear-and-tear' over life span. However, neuroendocrine pathways also regulate muscle mass in response to food availability. Such pathways might provide useful therapeutic approaches for combating muscle loss during aging. From this chapter, readers will develop a deeper understanding of the ways that C.elegans can be used for mechanistic gerontological studies.","PeriodicalId":87437,"journal":{"name":"Interdisciplinary topics in gerontology","volume":"37 ","pages":"84-93"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000319996","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29185133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

mTOR signaling as a target of amino acid treatment of the age-related sarcopenia. mTOR信号作为氨基酸治疗老年性肌少症的靶点。

Interdisciplinary topics in gerontology Pub Date : 2010-01-01 Epub Date: 2010-08-10 DOI: 10.1159/000319998

Giuseppe D'Antona, Enzo Nisoli

引用次数: 26

Changes in body composition in response to challenges during aging in rats. 大鼠衰老过程中应对挑战的身体成分变化。

Interdisciplinary topics in gerontology Pub Date : 2010-01-01 Epub Date: 2010-08-10 DOI: 10.1159/000319995

Tami Wolden-Hanson

{"title":"Changes in body composition in response to challenges during aging in rats.","authors":"Tami Wolden-Hanson","doi":"10.1159/000319995","DOIUrl":"https://doi.org/10.1159/000319995","url":null,"abstract":"Body composition changes over the lifespan of Brown Norway rats, in patterns similar to those of humans. Young adults are lean, with little fat, much of which is intra-abdominal. As they age, rats exhibit linear growth, and both lean and fat mass increase until late middle to early old age. Fat mass continues to accumulate throughout the lifespan, both viscerally and subcutaneously; aging animals carry a higher proportion of their fat mass peripherally. After middle age, skeletal muscle mass begins to decline, and sarcopenia develops when animals reach senescence. Finally, in late old age, or senescence, body weights begin to decline, and both fat and lean mass are lost. Healthy aged rats generally respond to negative energy balance challenges less robustly than younger adult animals, although they do appropriately regulate adipose tissue stores and preserve lean mass. The response to a positive energy balance challenge (high fat feeding) is less well regulated in aging animals, and dietary-induced obesity develops rapidly in aged animals. Here we present a summary of several studies of body composition in response to challenges of energy balance in aging male Brown Norway rats, with special emphasis on adipose tissue partitioning.","PeriodicalId":87437,"journal":{"name":"Interdisciplinary topics in gerontology","volume":"37 ","pages":"64-83"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000319995","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29185131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 27

Mitochondrial theory of aging in human age-related sarcopenia. 人类年龄相关性肌肉减少症的线粒体衰老理论。

Interdisciplinary topics in gerontology Pub Date : 2010-01-01 Epub Date: 2010-08-10 DOI: 10.1159/000319999

Gianni Parise, Michael De Lisio

{"title":"Mitochondrial theory of aging in human age-related sarcopenia.","authors":"Gianni Parise, Michael De Lisio","doi":"10.1159/000319999","DOIUrl":"https://doi.org/10.1159/000319999","url":null,"abstract":"Understanding age-related sarcopenia and, more importantly, devising counterstrategies require an intimate knowledge of the underlying mechanism(s) of sarcopenia. The mitochondrial theory of aging (MTA) has been a leading theory on aging for the last decade; however, there is relatively little information from human tissue to support or rebut the involvement of the MTA in aging skeletal muscle. It is believed that mitochondria may contribute to sarcopenia in a stochastic fashion where regions of fibers containing dysfunctional mitochondria are forced to atrophy. Resistance exercise, a known hypertrophic stimulus, has been shown to improve the mitochondrial phenotype of aged skeletal muscle. Furthermore, activation of skeletal muscle stem cells by resistance exercise may attenuate sarcopenia in two ways. First by inducing nuclear addition to postmitotic fibers, and, second, by increasing the proportion of functional mitochondria donated by muscle stem cells in a process termed 'gene shifting'. In this chapter we review the evidence supporting the MTA, the potential to attenuate the MTA with a known hypertrophic stimuli and explore the role of muscle stem cells in gene shifting to determine the connection between mitochondrial dysfunction and age-related sarcopenia.","PeriodicalId":87437,"journal":{"name":"Interdisciplinary topics in gerontology","volume":"37 ","pages":"142-56"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000319999","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29185135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18