Pub Date : 2017-06-01DOI: 10.12968/denn.2017.13.6.276
C. Wake
B ald and with wrinkly skin, the naked mole rat may not be the picture of youth, but these creatures continue to amaze us with their exceptionally long life. Naked mole rats are documented to live at least 30 years in captivity. But, they are not yet in the ranks of ‘gero-elites’: certain bats, for example, can live beyond 40 years (Podlutsky et al., 2005). Despite this longevity, naked mole rats show hardly any signs of getting older, such as problems with the heart, bones or metabolism. Females do not go through the menopause and continue to reproduce into their 30s. Even their cells have a remarkable resistance to oxidative damage (Edrey et al., 2011), and age-related chronic diseases, such as cancer, are rare. So far, most of what we know about this animal is based on studies with small sample sizes, making it difficult to determine how long-lived they really are. Now, in eLife, J. Graham Ruby, Megan Smith and Rochelle Buffenstein of Calico Life Sciences report how naked mole rats never cease to surprise (Ruby et al., 2018). A mathematical model called the GompertzMakeham law of mortality – which states that the risk of death increases exponentially with age – can be used to assess how long species live and what factors contribute to the mortality risk. Ruby et al. used this model to analyze an existing data set of 3,299 naked mole rats across a 30-year timespan and found that they did not conform to the Gompertz-Makeham law. In fact, their mortality hazard did not increase as they got older. This is unprecedented for mammals – one would not expect a small rodent such as the naked mole rat to live for more than six years, let alone show the first signs of aging at a time double its predicted maximum lifespan. Previous studies suggest that aging nonetheless creeps in: naked mole rats can accumulate oxidative damage in their cells and tissues (a sign of aging) and experience muscle wasting, and there is also some evidence for cancer (Edrey et al., 2011; Andziak et al., 2006; Taylor et al., 2017). This motivates further consideration of Ruby et al.’s demographic criteria so that we can understand why their data show an absence of Gompertz mortality accelerations. It can be assumed that when no deaths are observed in a group, there is still a risk of mortality – it may just be very low. However, when the number of deaths is low, errors in the sampling method could bias the estimates of the Gompertz parameters (Promislow et al., 1999). At its minimum measurable value, the death rate in a population is either 0 (no one dies) or 1 (a single individual dies). For the data studied by Ruby et al., this means that the minimum rate of mortality that can be accurately reported is 1/ 3,299: a baseline mortality of ~0.0003 per day. However, the baseline mortality reported in Ruby et al. is even lower (1/10,000 per day). This would indicate that their naked mole rat population is too small to correctly estimate the true mortality rate or the Gompertz paramet
年老且皮肤布满皱纹的裸鼹鼠可能看起来并不年轻，但这些生物却以其超长的寿命不断给我们带来惊喜。据记载，裸鼹鼠被圈养至少可以活30年。但是，它们还没有进入“老年精英”的行列:例如，某些蝙蝠可以活到40岁以上(Podlutsky et al.， 2005)。尽管如此长寿，裸鼹鼠几乎没有表现出任何变老的迹象，比如心脏、骨骼或新陈代谢的问题。女性不会经历更年期，并在30多岁时继续生育。甚至他们的细胞对氧化损伤也有显著的抵抗力(Edrey et al.， 2011)，与年龄相关的慢性疾病，如癌症，也很少见。到目前为止，我们对这种动物的大部分了解都是基于小样本量的研究，因此很难确定它们的实际寿命。现在，在eLife中，Calico生命科学的J. Graham Ruby, Megan Smith和Rochelle Buffenstein报告了裸鼹鼠如何永远不会停止惊喜(Ruby et al.， 2018)。一个被称为GompertzMakeham死亡定律的数学模型——它指出死亡的风险随着年龄的增长呈指数增长——可以用来评估物种的寿命和导致死亡风险的因素。Ruby等人使用该模型分析了现有的3299只裸鼹鼠30年时间跨度的数据集，发现它们不符合Gompertz-Makeham定律。事实上，他们的死亡风险并没有随着年龄的增长而增加。这对哺乳动物来说是前所未有的——人们不会期望像裸鼹鼠这样的小型啮齿动物能活超过6年，更不用说在其预期最大寿命的两倍时出现最初的衰老迹象了。先前的研究表明，尽管如此，衰老仍在悄悄发生:裸鼹鼠可以在细胞和组织中积累氧化损伤(衰老的迹象)，并经历肌肉萎缩，还有一些证据表明它会致癌(Edrey et al.， 2011;Andziak et al.， 2006;Taylor et al.， 2017)。这促使我们进一步考虑Ruby等人的人口统计标准，以便我们能够理解为什么他们的数据显示没有Gompertz死亡率加速。可以假设，当一个群体中没有观察到死亡时，仍然存在死亡风险-可能只是非常低。然而，当死亡人数较低时，抽样方法中的错误可能会使Gompertz参数的估计产生偏差(Promislow et al.， 1999)。在其最小可测量值下，人口死亡率为0(没有人死亡)或1(一个人死亡)。对于Ruby等人研究的数据，这意味着可以准确报告的最低死亡率为1/ 3,299:每天约0.0003例基线死亡率。然而，Ruby等人报告的基线死亡率甚至更低(每天1/10,000)。这将表明他们的裸鼹鼠种群太小，无法正确估计真实死亡率或Gompertz参数。事实上，要检测到衰老死亡率加速，需要的样本量远远大于3299人。版权归Beltrán-Sánchez和Finch所有。本文在知识共享署名许可协议下发布，该协议允许在注明原作者和来源的情况下不受限制地使用和再分发。相关研究文章Ruby JG, Smith M, Buffenstein R. 2018。裸鼹鼠的死亡率不随年龄增长而增加，这违背了冈伯兹定律。eLife 7: e31157。DOI: 10.7554 / eLife.31157
{"title":"Age is just a number","authors":"C. Wake","doi":"10.12968/denn.2017.13.6.276","DOIUrl":"https://doi.org/10.12968/denn.2017.13.6.276","url":null,"abstract":"B ald and with wrinkly skin, the naked mole rat may not be the picture of youth, but these creatures continue to amaze us with their exceptionally long life. Naked mole rats are documented to live at least 30 years in captivity. But, they are not yet in the ranks of ‘gero-elites’: certain bats, for example, can live beyond 40 years (Podlutsky et al., 2005). Despite this longevity, naked mole rats show hardly any signs of getting older, such as problems with the heart, bones or metabolism. Females do not go through the menopause and continue to reproduce into their 30s. Even their cells have a remarkable resistance to oxidative damage (Edrey et al., 2011), and age-related chronic diseases, such as cancer, are rare. So far, most of what we know about this animal is based on studies with small sample sizes, making it difficult to determine how long-lived they really are. Now, in eLife, J. Graham Ruby, Megan Smith and Rochelle Buffenstein of Calico Life Sciences report how naked mole rats never cease to surprise (Ruby et al., 2018). A mathematical model called the GompertzMakeham law of mortality – which states that the risk of death increases exponentially with age – can be used to assess how long species live and what factors contribute to the mortality risk. Ruby et al. used this model to analyze an existing data set of 3,299 naked mole rats across a 30-year timespan and found that they did not conform to the Gompertz-Makeham law. In fact, their mortality hazard did not increase as they got older. This is unprecedented for mammals – one would not expect a small rodent such as the naked mole rat to live for more than six years, let alone show the first signs of aging at a time double its predicted maximum lifespan. Previous studies suggest that aging nonetheless creeps in: naked mole rats can accumulate oxidative damage in their cells and tissues (a sign of aging) and experience muscle wasting, and there is also some evidence for cancer (Edrey et al., 2011; Andziak et al., 2006; Taylor et al., 2017). This motivates further consideration of Ruby et al.’s demographic criteria so that we can understand why their data show an absence of Gompertz mortality accelerations. It can be assumed that when no deaths are observed in a group, there is still a risk of mortality – it may just be very low. However, when the number of deaths is low, errors in the sampling method could bias the estimates of the Gompertz parameters (Promislow et al., 1999). At its minimum measurable value, the death rate in a population is either 0 (no one dies) or 1 (a single individual dies). For the data studied by Ruby et al., this means that the minimum rate of mortality that can be accurately reported is 1/ 3,299: a baseline mortality of ~0.0003 per day. However, the baseline mortality reported in Ruby et al. is even lower (1/10,000 per day). This would indicate that their naked mole rat population is too small to correctly estimate the true mortality rate or the Gompertz paramet","PeriodicalId":13728,"journal":{"name":"Inpharma Weekly","volume":"1 1","pages":"15-16"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88170015","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}
Pub Date : 2016-07-01DOI: 10.2165/00128413-200414200-00006
A. Freitas
{"title":"Progress in development of a malaria vaccine","authors":"A. Freitas","doi":"10.2165/00128413-200414200-00006","DOIUrl":"https://doi.org/10.2165/00128413-200414200-00006","url":null,"abstract":"","PeriodicalId":13728,"journal":{"name":"Inpharma Weekly","volume":"15 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84886281","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}
{"title":"WHAT’S NEW IN DEPRESSION?","authors":"S. H. Koh","doi":"10.1007/BF03298758","DOIUrl":"https://doi.org/10.1007/BF03298758","url":null,"abstract":"","PeriodicalId":13728,"journal":{"name":"Inpharma Weekly","volume":"27 1","pages":"20"},"PeriodicalIF":0.0,"publicationDate":"2016-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88412455","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}
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