Jonathan the 194-year-old tortoise could help humans live longer

St Helena Government

A new genetic analysis has revealed potential clues to the longevity secrets of a giant tortoise named Jonathan, the world’s oldest land animal . Researchers say the findings could eventually inform treatments aimed at slowing age-related cellular decline in humans.

Believed to be 194 years old, Jonathan is an Aldabra giant tortoise — a species native to the islands of Seychelles in the Indian Ocean — and he has spent most of his life on the remote South Atlantic island of St. Helena, a British Overseas Territory.

Giant tortoises are among the longest-lived land animals on Earth, with some records indicating they can regularly survive for more than a century. But Jonathan, approaching his 200th birthday, is an extreme example in this already special group.

Oceans Image/Photoshot/Sipa USA

The longest-living vertebrate could offer clues to extending the human lifespan, scientists say

One explanation for these animals’ extended lifespan might be that they take life very slowly — even at the genetic level, according to a new study published Wednesday in the journal Science Advances .

“The assumption has always been that their metabolic rate is very low compared to us,” said study coauthor Justin Gerlach, a fellow in biology at the University of Cambridge in the United Kingdom. “That means that the processes that are going on inside the cells are slower, so there are fewer chemical reactions and therefore less damage to the cells and to the DNA.”

Gerlach and his colleagues tested those assumptions by examining Jonathan’s genome — the complete DNA set — as well as his epigenome, the switches that turn genes on and off. The researchers found 287 gene variants associated with protecting the animal from the inevitable cellular damage that comes with time.

“He does have some genes that are particularly good for DNA repair and reducing inflammation,” said Gerlach, referring to two key mechanisms that are known to slow down aging processes.

More specifically, the analysis suggests that Jonathan can continue expressing the right genes at the right levels even in old age. This process typically starts to break down much earlier in most other animals, including humans, Gerlach said.

“Our cells start doing the wrong things and we get cancers, for example. But Jonathan has still got the genetic controls of a much younger animal,” he added. “We don’t know whether that’s because he is exceptional, or whether actually that’s what giant tortoises do. But it does mean that their bodies are much fitter than we would expect for their age, compared to what would happen with humans.”

Other members of the animal kingdom, including species of whales, sharks and clams, are also known to reach older ages, but scientists know little about the genetic and molecular mechanisms that drive an animal’s lifespan to be long or short, said Joao Pedro de Magalhaes, chair of molecular biogerontology at the UK’s University of Birmingham, who was not involved with the study.

“Understanding why some species live much longer than others would represent a major breakthrough in our understanding of ageing and longevity, with potential applications to human health,” he added via email.

Jonathan’s exact age is unknown. Scientists have estimated the great reptile is around age 194 based on a photograph from 1882 that depicts him in St. Helena already at adult size. Giant tortoises typically reach this size at about 50 years old, allowing researchers to deduce his current age from a photo taken 144 years ago.

Based on this estimate, St. Helena’s governor in 2022 gave Jonathan an official birthday — December 4, 1832; Abraham Lincoln, Charles Darwin and Queen Victoria would have all been alive then and in their young age.

However, Jonathan could be even older — 200 years old or more, according to Gerlach. The animal’s arrival in St. Helena was likely because the public in the 1800s regarded giant tortoises as “curiosities,” and as such he would have made for an interesting gift for a colonial administrator. This fate spared him from a far more gruesome one that was common for the species at the time. Crews on exploration vessels often captured the giant creatures and kept them as food supplies.

“The ships would collect tortoises from the Seychelles, the Galápagos or Mauritius, and they could keep them on board for months without bothering to feed them or give them water,” Gerlach explained. “They’d still be alive and edible. It was a grim practice that contributed to the extinction of the Mauritian species.”

Weighing about 400 pounds (180 kilograms), Jonathan is still active despite having lost his eyesight to cataracts. He is a popular tourist attraction, and earlier this year he was the subject of a viral April Fools’ Day joke that wrongly claimed he had died, prompting the government of St. Helena to confirm he was still alive and well.

Due to the animal’s old age and to avoid any risk of infection, the study authors collected DNA samples by swabbing his mouth, rather than drawing blood. The team noted that the saliva samples prevented the use of more accurate DNA sequencing techniques.

The researchers compared Jonathan’s DNA and epigenome with that of much younger members of his species found on the Aldabra Atoll of Seychelles and saw remarkable similarities. In addition, his mitochondria, the cell structures that produce energy, were in surprisingly optimal shape.

Gianluigi Guercia/AFP/Getty Images

Jonathan the tortoise, world’s oldest land animal, celebrates his 190th birthday

“We don’t yet know if this is common to his species, but one of our next goals is to analyze other Aldabra tortoises to find out,” said senior study author Dr. Stephen Clark, the founder of Kallel Foundation, a Nashville-based nonprofit dedicated to increasing human longevity.

“There is some data showing that mitochondrial health is important for long-lived species, and it has been shown that human supercentenarians have more efficient mitochondria, so our results in Jonathan fit with these findings,” Clark said in an email, referring to people who reach the age of 110 or more.

Jonathan’s genome offers a map for cellular resilience that could translate into treatments for people, Clark added. “We are very interested in finding generic human drugs that improve mitochondrial health, and we want to bring these drugs into human clinical trials within the next year or two.”

With a single animal, the new findings cannot tell researchers exactly why Jonathan has lived so long, and more giant tortoises and other long-lived species are needed to get a better picture of genetic drivers of longevity, according to Handan Melike Dönertaş, an assistant professor and genomics researcher at the Middle East Technical University in Turkey. She was not involved with the study.

“By comparing such extreme individuals with others, not only among humans such as centenarians, but also in other species, we can start to learn what makes them special, and with advances in medical technology we may find ways to apply what we learn,” she said in an email.

Jonathan is an ideal research subject for investigating genetic changes that may be linked to longer life, making the new study compelling, said Vincent J. Lynch, a professor in the department of biological sciences at the University at Buffalo in New York.

Courtesy Louise Bestea

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However, some of the study’s methods are prone to give false negative and false positive results, said Lynch, who was not involved with the work. “We’ve developed computational methods to determine if mutations are adaptive, good or deleterious,” he wrote in an email. “But these methods are very sensitive to assumptions we make about how genes evolve. The model they used, while common, makes unrealistic assumptions that can lead to good mutations being called bad and bad mutations being called good.”

Still, the study is a valuable complement to a growing body of research and further supports that giant tortoises are unique in their ability to defy expectations for lifespan and health, said Ylenia Chiari, an associate professor, faculty of Medicine & Health Sciences, at the University of Nottingham in the UK. Chiari has also studied the longevity of giant tortoise species in the Galápagos but was not involved in the recent work.

“These findings are beginning to unravel the complexity of the mechanisms that allow some organisms to achieve exceptional longevity,” Chiari said in an email. “Ultimately, one of the goals of studying these and other exceptionally long-lived animals is to gain insights that may be transferable to human ageing and cancer research.”

圣赫勒拿政府

一项新的基因分析揭示了名为乔纳森的巨龟长寿秘诀，乔纳森是世界上最长寿的陆地动物。研究人员表示，这些发现最终可能有助于开发延缓人类与年龄相关的细胞衰退的治疗方法。

据信已有 194 岁高龄的乔纳森是一只阿尔达布拉巨龟——一种原产于印度洋塞舌尔群岛的物种——它一生的大部分时间都生活在偏远的南大西洋岛屿圣赫勒拿岛上，该岛是英国海外领土。

巨龟是地球上寿命最长的陆地动物之一，一些记录显示它们通常可以活过一个世纪。但即将迎来200岁生日的乔纳森，在这个本就特殊的群体中，堪称一个极端例子。

海洋图片/照片/Sipa USA

科学家称，寿命最长的脊椎动物或许能为延长人类寿命提供线索。

根据周三发表在《科学进展》杂志上的一项新研究，这些动物寿命延长的一个解释可能是它们的生活节奏非常慢——甚至在基因层面也是如此。

“人们一直认为，与人类相比，它们的代谢率非常低，”该研究的合著者、英国剑桥大学生物学研究员贾斯汀·格拉赫说。“这意味着细胞内部发生的各种过程更慢，因此化学反应更少，对细胞和DNA的损伤也更小。”

格拉赫和他的同事通过分析乔纳森的基因组（完整的DNA序列）以及表观基因组（控制基因开启和关闭的开关）来检验这些假设。研究人员发现了287个与保护动物免受随着时间推移不可避免的细胞损伤相关的基因变异。

“他确实拥有一些特别有利于 DNA 修复和减少炎症的基因，”格拉赫说，他指的是两种已知可以减缓衰老过程的关键机制。

更具体地说，分析表明，即使到了老年，乔纳森仍然能够以适当的水平继续表达正确的基因。格拉赫说，在包括人类在内的大多数其他动物中，这一过程通常会在更早的时候就开始衰退。

“例如，我们的细胞会开始出现异常，导致癌症。但乔纳森仍然拥有远比它年轻得多的基因控制能力，”他补充道。“我们不知道这是因为他的特殊性，还是巨龟的普遍特征。但这确实意味着，与人类相比，它们的身体比我们预期的同龄人要健康得多。”

英国伯明翰大学分子生物老年学主席若昂·佩德罗·德·马加良斯（Joao Pedro de Magalhaes）表示，包括鲸鱼、鲨鱼和蛤蜊在内的其他动物王国成员也能活到更长的寿命，但科学家们对决定动物寿命长短的遗传和分子机制知之甚少。他并未参与这项研究。

“了解为什么有些物种的寿命比其他物种长得多，将代表着我们对衰老和长寿的理解取得重大突破，并有可能应用于人类健康，”他通过电子邮件补充道。

乔纳森的确切年龄尚不清楚。科学家们根据一张摄于1882年的照片估计，这只巨型爬行动物大约194岁。照片显示，它在圣赫勒拿岛时已经长到了成年体型。巨龟通常在50岁左右长到这种体型，因此研究人员可以根据这张144年前拍摄的照片推断出它现在的年龄。

根据这一估计，圣赫勒拿总督在 2022 年将乔纳森的官方生日定为 1832 年 12 月 4 日；亚伯拉罕·林肯、查尔斯·达尔文和维多利亚女王当时都还活着，而且正值壮年。

然而，据格拉赫称，乔纳森的年龄可能更大——至少有200岁或以上。这只巨龟出现在圣赫勒拿岛很可能是因为19世纪的公众将巨龟视为“奇珍异兽”，因此，它对殖民地官员来说会是一份有趣的礼物。这样的命运使它免于当时这种巨龟常见的惨状。探险船上的船员经常捕获这些巨型生物，并将它们作为食物来源。

“这些船只从塞舌尔、加拉帕戈斯群岛或毛里求斯收集陆龟，然后把它们养在船上几个月，既不喂食也不给水，”格拉赫解释说。“它们仍然活着，而且可以食用。这种残忍的做法导致了毛里求斯陆龟的灭绝。”

乔纳森体重约400磅（180公斤），尽管因白内障失明，但他依然活跃。他是一位颇受欢迎的旅游景点。今年早些时候，一个愚人节玩笑在网上疯传，错误地声称他已经去世，圣赫勒拿政府随后出面证实他仍然健在。

由于这只动物年事已高，为了避免感染风险，研究人员没有抽取血液，而是通过拭子采集其口腔样本来收集DNA样本。研究团队指出，唾液样本限制了更精确的DNA测序技术的使用。

研究人员将乔纳森的DNA和表观基因组与在塞舌尔阿尔达布拉环礁发现的同种生物中更年轻的成员的DNA和表观基因组进行了比较，发现二者之间存在显著的相似性。此外，他的线粒体（细胞中产生能量的结构）也处于出乎意料的最佳状态。

Gianluigi Guercia/法新社/盖蒂图片社

世界上最长寿的陆龟乔纳森迎来了它的190岁生日。

“我们还不知道这是否是该物种的普遍现象，但我们接下来的目标之一是分析其他阿尔达布拉象龟来找出答案，”该研究的资深作者、卡勒尔基金会创始人斯蒂芬·克拉克博士说道。卡勒尔基金会是一家位于纳什维尔的非营利组织，致力于延长人类的寿命。

克拉克在一封电子邮件中说：“一些数据显示，线粒体健康对长寿物种很重要，而且已经证明，人类超级百岁老人的线粒体效率更高，因此我们在乔纳森身上得到的结果与这些发现相符。”他指的是那些活到 110 岁或以上的人。

克拉克补充说，乔纳森的基因组为细胞韧性提供了一张图谱，这或许能转化为人类的治疗方法。“我们非常希望找到能够改善线粒体健康的通用人类药物，并希望在未来一两年内将这些药物推进到人体临床试验阶段。”

土耳其中东技术大学助理教授兼基因组学研究员汉丹·梅利克·德内尔塔什（Handan Melike Dönertaş）表示，仅凭一只动物，这项新发现无法确切地告诉研究人员乔纳森长寿的原因，还需要更多巨龟和其他长寿物种的研究，才能更好地了解长寿的遗传驱动因素。她并未参与这项研究。

她在电子邮件中说：“通过将这类极端个体与其他人进行比较，不仅包括百岁老人等人类，还包括其他物种，我们可以开始了解是什么让他们如此特别，随着医疗技术的进步，我们或许能找到应用我们所学到的知识的方法。”

纽约州立大学布法罗分校生物科学系教授文森特·J·林奇表示，乔纳森是研究可能与寿命延长有关的基因变化的理想研究对象，这使得这项新研究引人注目。

承蒙 Louise Bestea 惠允

一种不寻常的策略帮助一些热带蝴蝶的寿命比它们的近亲长25倍。

然而，林奇（他并未参与这项研究）指出，该研究的一些方法容易出现假阴性和假阳性结果。他在一封电子邮件中写道：“我们开发了一些计算方法来判断突变是适应性的、有益的还是有害的。但这些方法对我们关于基因进化方式的假设非常敏感。他们使用的模型虽然很常见，但却做出了不切实际的假设，这可能导致将有益的突变判定为有害突变，将有害突变判定为有益突变。”

尽管如此，这项研究仍然是对现有研究的重要补充，并进一步证实了巨龟在寿命和健康状况方面具有独特的优势，它们打破了人们对这些物种的预期。英国诺丁汉大学医学与健康科学学院副教授伊莱尼亚·基亚里（Ylenia Chiari）表示。基亚里也曾研究过加拉帕戈斯群岛巨龟的寿命，但并未参与这项最新研究。

“这些发现开始揭示某些生物能够实现超长寿命的复杂机制，”基亚里在一封电子邮件中写道。“最终，研究这些以及其他超长寿动物的目标之一是获得可能应用于人类衰老和癌症研究的见解。”