Travels through Time

Humans have long been fascinated with mortality. We are simultaneously mesmerized by and fearful of aging, with abundant popular culture around the idea of eternal youth and a myriad of antiaging products claiming to make us look or feel younger. Death is an inevitability of life, but planet Earth's diverse creatures have a fascinating variety of life spans. Mayflies live just one day while Antarctic glass sponges may live for 15,000 years. Understanding why longevity varies so greatly across the diversity of life forms is one of the most compelling mysteries of science. Even within populations of the same species, individuals can have extraordinarily different life spans. In the fields of ecology and evolutionary biology, aging research is breaking new ground, while biogerontology—the study of the biological processes of aging—is at work to extend health in older years. Hexactinellid sponges, also known as glass sponges, are one of the longest-lived organisms on Earth, thought to live as long as 15,000 years or more. Photograph: National Oceanic and Atmospheric Administration Photo Library. Why we age and then die is a paradox scientists and philosophers have grappled with since Aristotle. If natural selection acts to optimize fitness, why does evolution not prevent age-related decline? In 1891, German biologist August Weismann, piggybacking on ideas from ancient Roman predecessors such as the philosopher-poet Lucretius, suggested that selection for aging provides a weeding out of older individuals to provide room for more fecund youngsters. Later, beginning in the 1940 s, evolutionary biologists J. B. S. Haldane, Peter B. Medawar, and George C. Williams recognized the weakness in Weismann's explanation. It was premised on the flawed idea of group selection—that aging had evolved for the good of the species. Recognizing that natural selection acts on individuals, not groups or species, the trio proposed that aging evolves because, in general, the strength of natural selection declines with age. “That allows, through various mechanisms, for senescence to arise with age,” explains evolutionary ecologist Dan Nussey, University of Edinburgh. It took a few decades for researchers to nail down the theory, formalized mathematically by William D. Hamilton and Brian Charlesworth in the 1960 s and 1970 s. But now, says Nussey, it is widely accepted. The quest he now finds exciting is applying theory to understand why there are variations. Why are some organisms so extraordinarily long lived? Why do some species show very delayed, or debatably, no sign of the age-related declines known as senescence? And within populations, why so much variability in how individuals age? Research to answer these questions, he says, is “proving very, very challenging.” At the National University of Ireland Galway, Kevin Healy is interested in the macroecology of aging—the big patterns in animal evolution and ecology. “Everything lives, dies, reproduces; it doesn’t matter what you are,” says Healy. But with different animals doing different things, is there anything that links them? Are there broadscale fundamental patterns? These questions form the crux of his research. Looking across vertebrate and invertebrate organisms, Healy and colleagues conducted a broadscale analysis of how life history traits map onto life span, publishing their results in Nature Ecology and Evolution in July 2019. It is one of the biggest analyses of life history and life spans thus far, encapsulating data from 121 species across 11 clades spanning creatures including sea whips, clams, fish, elephants, humans, squirrels, turtles, vultures, and fulmars. Freshwater crocodiles have high mortality in early life, but once reproductively mature, they reproduce consistently until they die, characteristic of a classic type III survivorship curve. Photograph: MissMegido. What Healy and colleagues found, in support of the longstanding idea of a fast–slow continuum of lifestyles, is that if an organism is slow to mature, it tends to have higher survival past the juvenile stage and a long generation period, meaning it takes a long time for it to replace itself in the population. These are classic hallmarks of a slow life history. In contrast, some organisms are the opposite and live fast. Individuals have limited energy and resources to allocate toward reproducing or repair and maintenance, explains Healy. So there is an energy trade-off. Healy's 2019 analysis found that independent of the fast–slow continuum, other traits trade off with each other around how mortality and reproduction are spread across the life cycle. “It doesn’t matter how fast your life cycle is going; it's a question of whether you have it all bunched into one go, like salmon, where you produce one big clump and then you’re done,” he says, “or whether you’re more like the freshwater crocodile.” In the early life of freshwater crocodiles, there is high mortality, but once they are reproductively mature, they reproduce repeatedly until they die. Students of ecology are familiar with three main types of survivorship curves. By plotting the number of survivors per 1000 individuals on a log scale versus time, it was suggested, as early as the late 1920 s, that there are three patterns. Clumped mortality in early life gives the freshwater crocodile a classic type III survivorship curve. In contrast, in the developed world, modern humans have low mortality until older ages, most reaching 50–60 before any drop off in numbers. This is known as type I survivorship. Type II organisms have pretty constant mortality rates throughout their lives, a pattern seen in some birds. Healy is studying evidence for the existence of a fourth survivorship curve, for animals in which most offspring die in the first time step, “which is pretty common for fish,” says Healy. In examining the range of life spans, one of the classic patterns that has emerged, an idea dating back more than a century, is that bigger animals live longer. Evolutionary thinking behind a size advantage is that once an individual escapes the small-size danger zone, it has a high chance of surviving to old age. Bowhead whales, longer than a bus, can live for two centuries. Wild elephants can live into their 70 s. Mice, in contrast, seldom live more than 18 months in the wild. And most insects have even shorter life spans, the mayfly completing its life cycle in just 24 hours. Yet intriguing fodder for understanding aging can come from close examination of the exceptions to the size-life span relationship. Kyle Elliott, evolutionary biologist at McGill University, in Montreal, Canada, has long been fascinated with why some seabirds break the rules of aging. If you meet a pet dog on the street, or watch a stranger walk by, their appearance and behavior provide some pretty clear clues about age. A young dog may be rambunctious and energetic, and an old dog might have an arthritic stiffness to its gait and gray hairs around its muzzle. Similarly, smooth skin versus wrinkles on a human face provide hints about age. Such physical clues are “true of most mammals,” says Elliott. Seabirds, he explains, are an enigma. In the seabirds he has studied for the past several decades, visibly, “there's no real way to know if a bird is young or old,” says Elliott. Creatures such as hydra—tiny tentacled tubular freshwater polyps full of stem cells continuously renewing their body—are known to defy the typical process of aging. But they are very distantly related to humans, explains Elliott. In contrast, birds are homeotherm vertebrates with high levels of energy expenditure and share many of our physiological traits. Yet when it comes to some hallmarks of mammalian aging—telomere shortening, changes in collagen structure causing wrinkles, muscle structure and function, immunity, oxidative stress, and hormone level shifts—birds seem to get away without many of these signs. Mayflies live their whole lives in one 24-hour day. Photograph: Zapyon. Black legged kittiwakes look the same as young adults as they do as old ones, and appear to have several physiological traits that defy what in mammals are key characteristics of senescence. Photograph: Andreas Trepte. When he started capturing and marking black-legged kittiwakes on remote Middleton Island, in Alaska, 20 years ago, some of the birds were 5 or 6 years old. Now these same birds are 25–26 years old, and “they look the same,” he says. If it was not for the bands on their legs, logging the date of their capture decades before, these sleek birds would provide no clues that they have weathered such a passage of time. One focal hallmark of aging he has investigated is seabird telomeres. Telomeres are caps on chromosomes, their length influencing how many times a cell can successfully divide. “Once it divides too many times, these caps wear down… Eventually, the cell is no longer able to replicate without damage,” says Elliott. As a body grows older, telomeres typically shorten, and cells and tissues do not function as well. This process is thought to be associated with overall organismal senescence in mammals. But in several long-lived seabirds, Elliott and collaborators, including Alexander Kitaysky and Rebecca Young of the University of Alaska Fairbanks, have found that telomere length does not shrink with age, and it may even grow. These birds have high levels of the enzyme telomerase, which prevents shortening with age, “so it will grow the telomeres, and repair any damage,” he explains. Lack of senescence in muscles, immune function, and oxidative stress are additional enigmas that Elliott revealed in seabirds. This puzzling lack of evidence for physiological senescence may be a trait of many long lived seabirds, explains Elliott, with similar findings emerging for albatrosses and storm petrels. In contrast, short-lived birds such as zebra finches and tree swallows show patterns a bit more like mammals. One long-neglected taxonomic group in the study of aging is plants. When Roberto Salguero-Gómez joined the Max Planck Institute as a postdoc to work with more than 300 leading researchers in senescence, “I was the only plant biologist in the institute,” he says. Early in his studies, Salguero-Gómez realized that scientists know very little about aging in plants. Whereas, in some trees, it is possible to count annual growth rings to establish their age, that only works with woody species. Even within those, it is mainly temperate species that tend to have true rings. “Most plants, which are herbaceous, don’t form rings as they age,” he says. That makes it difficult to establish whether senescence is the exception or the rule across the tree of life. Soay sheep tagged as babies and followed through their whole lives help researchers on the Scottish isle of St. Kilda to better understand mammalian senescence and aging. Photograph: Arpat Ozgul, University of Zurich. Clues about age are visible on the human face. Wrinkles are caused by age-related changes in collagen. Photograph: Wilfredor. Using a comparative framework, Salguero-Gómez's group at the University of Oxford examines conditions under which senescence evolves. Many plants, his group has found, escape from senescence. “If you think about the clothes that you’re wearing, the food that you had for breakfast today, or your laptop sitting on a wooden table, all of that is likely the product of plant species not having undergone drastically fast senescence,” he says. Had they undergone senescence, they would have lost vital functions as they grew larger, such that wood, roots, fruits, foliage, and ecosystems services would be lessened and of lower quality. Plants are special in that unlike cutting off a human limb, if you cut off a tree branch, “not only would the tree not die, but you would probably be promoting regrowth.” Regrowth or regeneration is something most animals do not do. Because most plants do not have differentiated cells, they can regrow fresh tissue that has not undergone senescence. This flexibility and regenerative ability makes plants drastically different from most animals, with the exception of peculiar ones such as the metazoan hydra that also has cells that are not fully determinate and does not show senescence. The list of animal species known to have negligible senescence is small so far, including the olm (an aquatic ­salamander), Blanding's turtle, eastern box turtle, Nile crocodile, rougheye rockfish, Red Sea urchin, and ocean quahog clam. Extreme longevity ­species, such as the Great Basin bristlecone pine or the Utah quaking aspen, might hold the key to why some species, including humans, undergo a drastic loss of functionality with age, whereas others do not. Like most mammals, dogs show visible signs of their age. At the National Institutes of Health, they are learning new tricks from old dogs — family pets, living at home, are enrolled in a study cohort to test interventions that might enhance health in old age. Photographs: Garrett 222 (left) and Tsaag Valren (right). Nussey, who investigates individual differences in how animals age, studies a population of Soay sheep on the Scottish isle of St. Kilda. The sheep have been studied closely for 35 years, with individuals marked at birth and closely monitored until their natural death. “We know everything about them—who their relatives are, the environmental and infection challenges they experience, where they live, who they socialize with, when they breed, how their offspring fare, and exactly when they die. We also catch them regularly and collect blood samples so we have a means of looking at their physiology longitudinally. There are few studies of mammals apart from humans (let alone wild mammals) with this quality of lifelong data,” says Nussey. “For me, the big question is what kinds of physiological decline underpin declines in survival and fertility in wild populations?” says Nussey. Are they the same kinds of processes that humans and lab animals undergo or different ones? Do the processes vary across species and ecological conditions? Likely they do, “because the environmental pressures organisms face to breed and survive vary so much,” he says. “But we have very limited understanding.” In the wild, it was long thought that animals did not live long enough to undergo senescence, with death by predation, disease, and starvation more likely scenarios. But late‐life declines in performance are now widely documented in the wild. A 2013 paper by Nussey and colleagues in Ageing Research Reviews noted evidence for senescence in 175 different wild animal species from 340 separate studies of birds, mammals, other vertebrates, and insects. Nussey suspects the updated number is much higher. Evidence of senescence of immune function, well known from human research, is emerging from wild animals too. A July 2019 Ecology Letters meta-analysis by Anne Peters at Monash University in Melbourne, Australia, revealed that aspects of immune function decline with age in wild animals, just as in humans and lab models. How this connects to late-life survival and fitness is still poorly understood. Nussey also has work in progress examining immune function in Soay sheep across the lifetimes of individuals to see what happens in old age and how it affects survival. Not surprisingly, human aging is a significant and heavily funded research focus. The stakes are high. That is because aging is the main risk factor for human disease, explains Felipe Sierra, director of the Division of Aging Biology at the National Institute on Aging (NIA), at the National Institutes of Health (NIH). Much of the emphasis in human aging research is focused around the identified “pillars” or “hallmarks of aging,” which include things like the stability of our genes, inflammation, adaptation to stress, and metabolism. Humans are such a long-lived species that it creates special challenges for researchers. 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