Trends Between Senescence, Longevity, and Internal Biological Properties in Living Organisms 

Alex Butler, Sophie McLean, Alexandru Toma, Kevin Xu

Abstract

An aspect of life that almost any living organism seems to have to deal with is senescence, or the biological ageing and gradual deterioration of the body as time passes. Although the theories as to why ageing occurs in lifeforms are plentiful and vast, and despite the various and unique adaptations many organisms have evolved throughout the years to delay these age-related deteriorations, one undeniable truth is that ageing is an unavoidable aspect of life. Scientific studies in this domain are essential to understand how organisms improve their longevity and quality of life, as well as how we can improve long-term health and optimally prevent physiological decay. Extensive scientific research has allowed us to locate factors that influence and positively correlate to the length of the lifespan of an organism and edge them closer to death. Two of the best indicators for determining an approximate lifespan of an animal are metabolic activity and body and brain size. Greater metabolic activity typically leads to a shorter lifespan, and larger body and brain size correlates to better. Naturally, there are exceptions to these trends, which can provide even more information about ageing process. Additio­nally, a major physical change that is often accompanied by ageing is the overall stiffening or loss of resilience in the body. These qualitative observations provide us with insight into variables within organisms’ day-to-day lives that affect their longevity and help us better understand why different species live longer than others, as well as why different species age differently, given their specific internal and environmental conditions. 

Introduction

The concept of ageing is common for any living organism, regardless of its manifestation or the longevity of a given specimen. It is natural and logical that immortality is unobtainable. All living beings experience cycles of life and death.  From a biological perspective, analyzing ageing is a challenging prospect—ageing is a complex process. No matter their species, each living organism exists, lives and evolves under unique conditions. Ageing as a process is defined by the physiological decline of an organism with time. It is pertinent for us to question the purpose of ageing, how it is triggered, how it generally functions, and how it affects an organism’s day-to-day life. Conversely, it is more empirically feasible to consider how an organism’s life affects its ageing, which is also known as its lifespan. Research around the concept of physiological deterioration is essential because it allows us to understand how an organism’s environment and actions often lead to its progressive decline in health. A complete comprehension of these processes could potentially help maximize lifespan for all kinds of animals, effectively diminishing the ramifications of ageing and improving overall health in different ecosystems. Among the repercussions of ageing, muscle weakening and lowering metabolism are prominently recognized. This research paper aims to expand this view by exploring various aspects of ageing, as well as the impact of several fundamental physical properties of biological organisms upon lifespan. The research highlighted in this article elaborates on the metabolic, evolutionary, cardiovascular, biomechanical, and physiological trends relating an organism’s operation with its longevity. Through field studies and logarithmic, physical, and biomechanical models, many theories and hypotheses have been conjectured to explain how numerous factors alter an organism’s lifespan. It was found that body mass, reduction of basal metabolism rate, and behavioural changes over time serve to primarily explain the decreasing metabolism in most organisms, which can lead to longer and more sustainable lifespans, while the accumulation of oxidative stress in tissues causes long-term damage and conversely shorten longevity. Moreover, trends amongst physiological characteristics of different species were denoted with respect to lifespan. Certain sex-specific qualities, along with unique body mass at peak maturity, the degree of cognitive development and encephalization, as well as the growth rate during stages of youth have been shown to reliably correlate with longevity. Models were used to show that male longevity is favoured in certain organisms, and females were advantaged in others, while also proving that species with larger body mass and proportionately larger brain mass typically tend to have longer lifespans. The growth rate in populations of a species also demonstrated that accelerated growth provided short-term benefits but compromised longevity, whereas slower, controlled development provided a longer lifespan along with more physiological fitness and integrity. Additionally, cardiovascular, and muscular development were both shown to decrease with time in response to environmental and behavioural changes. The resilience of arteries, tendons, ligaments, and other connective tissues, faced with repetitive and often damaging extensions and contractions suffered from increasing stiffness over time, while also offering opportunities for certain organisms to adapt and evolve fibres and proteins that aim to provide unhindered locomotion and support an entire healthy lifetime, without worrying about repair, wear, or loss of efficiency.

Metabolic and Behavioural Trends in Ageing Organisms

Organisms across the kingdom Animalia experience change in basal metabolic rate with age. Metabolism is the set of all chemical reactions within an organism that sustain life. There are four types of potential energy present in biological systems: chemical, spring, thermal, and electrostatic; metabolic reactions allow conversion between these four types of energy and kinetic energy. Metabolic rate refers to the speed at which these reactions are carried out, and therefore the rate of energy expenditure for the organism. The body mass and age of the organism are the largest determinants of basal (resting) metabolic rate, but it may also be determined by environmental and seasonal factors. Some reptiles can adjust their metabolism in accordance with weather conditions, and others may lower their metabolism in times of food scarcity to conserve energy (Robert et al., 2007). 

In one of the first theories of ageing, the ‘rate of living theory’, ageing, metabolism, and body mass were all thought to be directly linked due to the general observation that larger organisms typically have slower metabolic rates and longer lifespans. There are numerous exceptions to this theory, however. Birds defy this rule exceptionally, as many avians experience 3 times the lifespan as mammal species with similar body mass, while also exhibiting a higher metabolism (Holmes et al., 2001). The newer ‘free radical theory of ageing’ postulates that ageing results from the accumulation of tissue damage caused by reactive oxygen species (ROS), a byproduct of regular metabolic processes, most notably mitochondrial ones. ROS can bind to and deform all 4 of the major cellular macromolecules (proteins, lipids, nucleic acids, and carbohydrates) causing tissue damage. Some organisms that lower their metabolisms for lengthy periods of time, such as hibernating mammals, exhibit extended lifespans as ROS production decreases. The honey bee (A. mellifera)workers combat damage from ROS by spending the first few weeks of their adult life in their ‘nursing stage’ where they rarely fly, and later transition to foraging activities that involve lengthy flight. The early onset of foraging behaviour leads to decreased lifespan and more tissue damage due to ROS (Lane et al., 2014). 

While the ROS produced by metabolism results in ageing, ageing affects metabolic rate in turn; metabolic rate generally decreases with age. This occurs primarily due to a reduction in basal metabolic rate (the calories required to keep an organism alive at rest) and behavioural changes in organisms that result in reduced muscle mass and accordingly in the energy required for locomotion. The reduction in basal metabolic rate could occur for several reasons, such as the loss of metabolically active body mass or a reduction in sympathetic nervous system activity (Zafon, 2007). Behavioural changes, specifically activity level, account for the majority of metabolic change with age, as organisms tend to show a decrease in physical activity with age. This change in metabolic rate occurs rapidly in the adult stage of the Colorado potato beetle (L. decemlineata). One study found that the potato beetle’s resting metabolic rate peaked on the second day after emergence, followed by a gradual decline, where, by the tenth day, the beetles had the same metabolic rate as their first day (Fig. 1.) (Piiroinen et al., 2010). The graph shows the metabolic rate of the adult beetles, measured by CO2 production, with respect to time. The change in metabolic rate is a product of the exceptional change in energetic demand during the beetle’s first few days after emergence. During the first few days of their life, the beetles must expend energy developing flight muscles as well as reproductive organs, which may account for the higher resting metabolic rate. Female beetles had a more prolonged peak metabolic rate that lasted until about 4 days after emergence, due to the higher energetic cost of developing ovaries relative to male reproductive organs. The resting metabolic rate of the potato beetles decreased significantly after the completion of organ and muscle development as energy demand had decreased. Along with organ development, body temperature regulation also plays a large role in the determination of basal metabolic rate. The giant anteater(M. tridactyla) exhibits a relatively slow metabolic rate over its entire lifetime due to its relatively low body temperature (27–33 °C) that can fluctuate by up to 6 °C daily. The anteaters conserve energy through their lack of thermoregulation, as well as their behaviour, spending on average 16.25 hours a day at rest. Even this relatively low metabolic rate decreases with age as the activity level of anteaters declines. The slow metabolism and therefore low energetic requirements of these animals often leads to them being overfed in captivity and growing to almost twice their size observed in natural environments (Stahl et al., 2011).

The rate of senescence of an organism is considered an evolved phenotype. Traits that sacrifice the fitness of an organism in the early stages of life for the benefit of fitness later in life are unfavourable, so the health of ageing organisms is often neglected in natural selection. Some organisms, predominantly snakes and other reptiles, combat the energetic disadvantages of ageing through increased fecundity with age, and this combined with indeterminate growth allows them to evolve negligible senescence (Bronikowski, 2008). Organisms evolve to delay senescence in cases where older individuals are more likely to survive long past sexual maturity or when their presence ensures the survival of younger individuals. One of the most prolonged lifespans relative to body mass in mammals is that of the naked mole-rat (H.glaber). These small approximately 40 gram rodents native to Northeast Africa can live to more than 22 years of age in captivity, with the oldest individual on record living to more than 28 years of age. The longevity quotient of naked mole rats is at least 9, indicating that, based on trends between lifespan and body mass across organisms, their life span is 9 times longer than predicted (O’Connor et al., 2002). Animals with high mortality rates often evolve low maximum ages and early reproduction. Naked mole rats, however, have subterranean lives underground in a network of tunnels where mortality due to predation or climatic events is very low. This makes it more energetically favourable for naked mole rats to evolve long lifespans. Only one female in the colony of approximately 70 rodents will breed, and the rest of the rodents perform tasks for the colony into their old age, contributing to the continuation of the species. Naked mole rats may achieve their advanced age through lower lifelong metabolism. The rodents invest very little energy into predatory defences due to their sheltered environment. Naked mole rats are also practically cold-blooded, they invest little energy in thermoregulation, instead, body temperature is regulated by huddling in groups, or by basking in hotter tunnels close to the surface. Naked mole rats show a decrease in activity with age, but a negligible decrease in basal metabolic rate. The low metabolic rate of naked mole rats may be the source of their increased longevity through the slowing of production of damaging ROS.

Some organisms, such as the giant pacific octopus (E. dofleini), will die off after their first reproduction and therefore do not evolve senescence. However, the majority of organisms will live past their first reproduction to produce more offspring or care for existing offspring. While living among younger generations, ageing individuals must find some way to avoid competition with their young to ensure the continuation of the species. According to the ‘thrifty aged’ hypothesis, the lower metabolic rate of aged organisms is an evolved trait to reduce their energy demands to increase energy availability for their young. 

Physiological Trends in Ageing Organisms

When discussing a topic such as ageing, a tremendous amount of internal and external factors come into play. Many researchers worldwide attempt to recognize patterns regarding the phenomenon of physiological decline with time and study trends between different physiological properties and their relationship to the lifespan of their respective species. These characteristics range from the number of rings visible around the cross-section of a tree trunk to the difference in longevity between a queen ant and its workers. Considering the broadness of this research, there are three outstanding fields of study regarding ageing and physiological qualities; sex-specific characteristics, levels of encephalization and allometry, and the rate of growth of the biological organism. These three topics will be discussed to understand their implications in an organism’s lifespan and determine patterns that may better help understand why certain organisms age the way they do.

 A physiological dynamic that is seen across many species, and especially insects, is sex-specific lifespan. Sexual selection has a noticeable role in how males and females of a species age because of the organism’s fundamental objective of reproduction. The general theory of sexual selection implies that an organism’s lifespan is, to some degree, dictated by its reproductive ability and efficiency. If specific sexes of a species decline in reproductive ability over time faster, these sexes are expected to also age faster and live shorter lives. This concept can vary greatly among individuals due to countless factors. In different nematode species, variables such as the mating system, same-sex isolation and dietary restrictions affect how males and females age. However, with laboratory experiments controlling these conditions, male roundworms (C. elegans) live longer than females, and the opposite is true for P. exspectatus nematodes, for instance (Ancell & Pires-DaSilva, 2017). Such sex-specific correlations are also observable in insects such as the decorated tropical house cricket (G. sigillatus), where field studies have shown that male crickets age considerably shorter and hold longer lifespans than females (Archer et al., 2012). This trend is supported by the fact that the males’ callings increase with age, whereas female fecundity decreases. The reproductive ability of the male refines over time, but not the female’s, which explains the sexual selection occurring in female crickets. It is also pertinent to notice that the sexual difference in lifespan is much more pronounced in smaller, insect-like organisms, which is why other studies need to be discussed to understand the lifespan of larger animals.

The overall size and proportions of an organism’s body and brain, known respectively as the study of allometry and encephalization, help scientists view a general trend in longevity between species of animals. These two allometric principles are known to account considerably for the variation in average lifespans of different organisms. Encephalization and body size are two facets of the same die; both share the same conceptual tendency. Larger adult size in a species is linked to that species’ controlled ageing and greater longevity. Similarly, species with proportionately larger and developed brains observe longer lifespans. Moreover, physical and logarithmic models confirm these findings and even allow researchers to roughly predict the lifespans of different warm-blooded mammals and insects using their body and brain weight (Fig. 2) (Hofman, 1993). The accuracy of these predictions was estimated at 60% for body weight and 80% for brain weight. As seen in the below figures, the data spread for organisms assessed through brain weight is visibly lesser than those assessed by body weight, which illustrates and explains the difference in the aforementioned prediction accuracies.

From these theories of encephalization, insectivores like the giant anteater (M. tridactyla) and rodents such as the canyon mouse (P. crinitus) have lower encephalization levels and thus live shorter lives. Conversely, more developed beings, such as primates and the common chimp (pan troglodytes) have longer lifespans. Encephalization is primarily used in longevity estimations due to its higher predictive accuracy. Of course, factors behind encephalization explain why proportionately larger brains in organisms lead to longer lives. The “expensive brain” hypothesis suggests that a more developed brain requires more metabolic attention, thus leading its organism to compensate by managing energy allocation and reducing growth costs. This prolongs development and reproductive cycles, which ultimately increases lifespan (Minias & Podlaszczuk, 2017). Examples of organisms respecting this ageing trend are Galliformes, which include the Japanese quail (C. japonica) and the red junglefowl (G. gallus), as well as Anseriformes like the northern shoveler (A. clypeata) and the tundra swan (C. columbianus). Another important factor in such allometric studies to consider is how these animals reach their maximal sizes and brain development, as well as the additional effects of this growth process on their longevity.

 As mentioned before, all animals have a unique rate of growth which develops them towards maturity and adulthood. In most cases, organisms prefer to grow at an accelerated rate because of extrinsic mortality factors, such as predation, and other motives, like the development of defensive mechanisms. Additionally, a fully grown animal can provide better nutrition, resources and reproductive ability, and, according to the definition of Darwinian fitness, every organism should aim to grow as quickly as possible to attain this optimal reproductive and physiological fitness (Metcalfe & Monaghan, 2003). However, the reason why not all species grow in an enhanced fashion is due to the fitness detriments and lesser longevity this growth paradoxically causes. Naturally, rushing a natural growth process can lead to less efficient biomechanisms, steps being skipped in the specimen’s development, and the overall reduction of one’s lifespan. This “live fast, die young” lifestyle can be favoured in some cases, especially when the organism’s goal is to reproduce efficiently and quickly and then die off. In other cases, long-term survival is jeopardized and the organism’s biomechanisms are less reliable, which leads to quicker long-term deterioration and accentuated ageing. An interesting example of this can be seen in pumpkinseed fish, (L. gibbosus) where different populations will favour accelerated growth to overcome predatory risks and reduce the vulnerability period of the young. In return, these quickly matured populations had more penetrable and weaker scales, which put them at greater risk of predation and affected their swimming efficiency long-term (Arendt & Stark, 2003). Similar tendencies were even found in reptiles; a study surrounding the southern snow skink (N. microlepidotus) showed that skinks with better foraging abilities tended to grow much faster, yet faced considerably higher mortality rates once released in the wild (Olsson & Shine, 2002). This was generally caused by the enhanced growth process, which allocated resources to different body components in ways that compromised the skinks’ defensive mechanisms and skeletal integrity. Therefore, growth rate has a significant impact on lifespan and even quality of life for many different organisms. Other factors, such as sex-specific characteristics, encephalization, and allometric dimensions also play a role in a studied organism’s expected ageing processes and longevity. 

Deterioration of the Cardiovascular System with Ageing

No matter their scale or environment, vertebrates are reliant upon a circulatory system for survival. Composed of a heart and blood vessels, the circulatory system is a closed system that transports both blood and nutrients throughout a body. The heart contains two types of chambers: atria and ventricles. Atria accept blood from the blood vessels into the heart, whilst ventricles discharge blood into the blood vessels. Reptiles, with the exception of crocodiles, have a heart with 3 chambers, two atria and a ventricle. The ventricle of a 3 chambered heart is subdivided to prevent the mixing of oxygenated and deoxygenated blood. Oxygenated blood arriving from the lungs is temporarily stored within a cavity, the cavum arteriosum, whilst deoxygenated blood passes through the ventricle. Mammals and birds have a 4 chambered heart composed of two atria and two ventricles. The left ventricle pumps blood from the heart to the aorta, from where it can circulate through the body. Blood flow from the ventricles, termed cardiac output, is determined by heart rate and ventricular stroke volume, the volume of blood ejected from the ventricle due to the contraction of the heart muscles. With age, the left ventricle (LV) of rats progressively changes. The connective tissue, myxoid, lining the valves of the ventricle thickens as a result of the accumulation of long linear polysaccharides known as glycosaminoglycans. Additionally, the myocytes, the cells within the heart tissue, experience hypertrophy with ageing. Together, these changes cause a net increase in LV mass, diameter, and wall thickness as rats age (Droogens et al., 2009). This leads to an increase of vascular resistance and can cause the heart’s atrial and mitral valves to not close properly, allowing blood to flow backwards through the heart. This phenomenon, known as vascular regurgitation, decreases ventricular stroke volume, as the heart must contend with a flow against the direction of pumping. The added work caused by vascular resistance and backflow increases blood pressure, likely eventually causing hypertension. In another study on rats, it was shown that the decreased cerebral blood flow caused by hypertension directly impaired associative learning and memory (Meneses et al., 1996). This implies that rats become less capable of recalling and adapting to their environment as they age, making them both vulnerable to predators and less capable of providing for themselves.

Unlike vertebrates, insects do not pump blood; they pump hemolymph. Hemolymph is a bodily fluid that, like blood, is composed mostly of plasma. Hemolymph transports nutrients throughout the body but differs from blood in that it does not transport oxygen, nor does it contain red blood cells. Insects are also distinguishable from vertebrates by their open circulatory system. Insects do not possess blood vessels. Instead, the majority of an insect’s circulatory system can be found in a singular dorsal vessel spanning the entire length of its body. The anterior of the dorsal vessel, known as the aorta, serves as a conduit for hemolymph flowing to the head. The posterior section of the dorsal vessel is segmented, forming a chain of thickly walled cavities separated by valves. The contraction of lateral muscles behind the walls of each chamber enables the pumping of hemolymph through the dorsal vessel, from posterior to anterior. This segmented posterior section is known as an insect’s heart. Thus, similarly to vertebrates, insects have a heart rate. Notably, some insects see a decrease in heart rate with old age. In the house cricket, heart rate decreases after the first six weeks of adulthood (McFarlane & Fong, 1972) and in the fruit fly Drosophila melanogaster “…the adult heart rate decreases with age, with older adults experiencing more cardiac arrhythmias and heart dysfunction than their younger counterparts” (Paternostro et al., 2001). Mosquitos see a net increase in heart rate through the first three-quarters of their life, but a net decrease in the last quarter (Doran, et al., 2017).  The trend of decreasing heart rate with age also persists in many mammals. C57Bl/6 mice experience a decline in heart rate with age (Cornelli et al., 2020). Similar to mosquitoes, rats also see a net increase in heart rate early in life and a decline with age. A study on pair-caged, male Fischer 344 rats models this trend, with the notable exception of a spike in heart rate near-death (Fig. 3) (Baskin et al., 1979). Reduction in heart rate can lead to oxygen deprivation, but heart rate with senescence is relatively insignificant when not accounting for other degenerative conditions.

Stifening and Locomotive Trends in Biomechanical Components of Ageing Organisms

Another aspect of ageing and senescence, the deterioration of the body that comes with age, that occurs in many living organisms is the overall stiffening or loss of resilience of the body and its components. It is precisely the deterioration of various levels in different systems that causes changes in the components of the living organism. These components could be tissues such as muscles, tendons, and even skin. An explanation for the stiffening that is seen in old age could be the “irreversible age-related changes in fibrous proteins” (Rockstein and Miquel, 1973) such as collagen and elastin. Connective tissues make up a major part of the mammalian physique. They include an abundance of assorted tissues whose main role is to maintain internal bodily shape. A major category of the connective tissues, dense regular connective tissues, is characterized by its amount of collagen compared to the ground substance, which contains all of the extracellular matrices. Tendons and ligaments are part of this subcategory and can be observed to have high amounts of collagen fibres all arranged in a parallel fashion. The principal distinction between tendons and ligaments is that tendons connect bones to muscles, while ligaments connect two bones. Tendons and ligaments can store great amounts of energy and have varying degrees of stiffness to better cope with specific needs based on the position it holds in the body. Ligaments play a pivotal role in stabilizing the joints and restricting movement in the joint to a fixed range of directions which is why they are found more often in or surrounding joints. Nevertheless, one thing that is common in most animals that display senescence is that these tendons and ligaments both lose their resilience and suffer a reduction in the ability to store potential energy as old age begins to take hold. In an experiment, Addis and Lawson (2010) used the established notion that as equines, or most animals for that fact, age, the tenocytes present in tendons, which produce collagen and are essential to the maintenance of integrity in the connective tissues, begin to deteriorate and tendon synthesis comes to a halt. They found that “the gradual decrease in mechanical integrity can result in the tendon no longer being able to withstand the loads placed on it” (Addis & Lawson, 2010).

Another aspect of stiffening in the body as one ages is the stiffening of the arteries. Similar to the stiffening in the tendons and ligaments, in the arteries, “elastic fibres have an extremely low turnover rate in vivo, and this longevity allows for the accumulation of age-related changes caused by fragmentation and calcification” (Kohn et al., 2015). As there are fewer and fewer elastin fibres in the arteries and stiffer and stiffer collagen, the arteries lose their resilience over time. This effect in the body has been shown to lead to many vascular diseases, and thus plays a major role in the longevity of a species. The naked mole-rat is a species that seems to lack this trait. As “aged individuals do not display deteriorated cardiovascular function (e.g. […] arterial stiffening)” (Mikuła-Pietrasik et al., 2020). The naked mole-rat is the “longest-lived rodent known, with a maximum lifespan potential (MLSP) of >31 years” (Grimes et al., 2014). This species of rodent appears to have “pronounced stress resistance, particularly resistance to the harmful effects of oxidative stress” (Grimes et al., 2014) and seems to be free of any sort of deterioration common to most ageing animals until “their last quartile of life” (Grimes et al., 2014). 

Insects are a vast category of living organisms and have developed much earlier than most warm-blooded animals. As an exceptionally fit group of invertebrates, insects have evolved and developed many physical elements extremely potent and precise. Although insects may have very different morphologies when compared to mammals, reptiles, or amphibians, they have often developed many similar organs or body parts that function comparably to those in mammals. One example of this concerns the tendons and ligaments in insects. With some insects needing to execute extremely powerful jumps several times their height such as the katydid or bush cricket, scientists have detected the presence of a protein called resilin, which has an extremely high elastic efficiency and “an ability to stretch three times its original length in reversible fashion over repeated stretching and relaxing cycles” (Oh et al., 2017). Although the high resilience of resilin suggests that its presence in an insect’s body must last the entire lifetime of the insect without getting replenished or changed and keep its resilience after hundreds of millions of extensions and contractions, it has been shown that the resilin is actually discarded and replenished during each moulting cycle and even increases in size in order to accommodate the increased mass of the insect (Burrows, 2016). Of course, resilin will begin to wear and fatigue over time, but this replenishment through moulting is a unique and exciting adaptation that has emerged from insects and arthropods to counter the effects of ageing as they require their tendons to be extremely efficient until the end of their lifetimes.

Conclusion

It is unreasonable for an organism to live forever, and neither is it favourable from an evolutionary standpoint. Natural selection favours successful reproduction over the longevity of individuals. Organisms are not indestructible; living mechanisms deteriorate over time. Ageing compromises the health of an organism through decreased cardiovascular efficiency, tissue resilience, neural function, and basal metabolism. This leads to increased vulnerability to predators, decreased ability to provide for oneself and, in due course, death. This highlights a challenge faced universally by all species: increasing their longevity. Naturally, different life forms have evolved distinct traits and behaviours to increase longevity by combatting the effects of ageing. This is most often accomplished through the redirection of energy during growth, which can result in fluctuations of growth rates and brain development, the slowing of ROS accumulation, and accelerated reproduction before death. However, the disparity in longevity among various species indicates that not all creatures have adapted equally well to face this challenge. Ultimately, ageing is inevitable, and the optimization of an organism’s anti-ageing parameters offers limited benefits for improving the quality and duration of a species’ lifespan; life cycles will and must perpetually continue.

References

Addis, P. R., & Lawson, S. E. (2010). The role of tendon stiffness in development of equine locomotion with age. Equine Vet J Suppl(38), 556-560. https://doi.org/10.1111/j.2042-3306.2010.00296.x

Ancell, H., & Pires-daSilva, A. (2017). Sex-specific lifespan and its evolution in nematodes. Semin Cell Dev Biol, 70, 122-129. https://doi.org/10.1016/j.semcdb.2017.05.012

Archer, C. R., Zajitschek, F., Sakaluk, S. K., Royle, N. J., & Hunt, J. (2012). Sexual selection affects the evolution of lifespan and ageing in the decorated cricket Gryllodes sigillatus. Evolution, 66(10), 3088-3100. https://doi.org/10.1111/j.1558-5646.2012.01673.x

Arendt, J., Wilson, D. S., & Stark, E. (2001). Scale strength as a cost of rapid growth in sunfish. Oikos, 93(1), 95-100. https://doi.org/10.1034/j.1600-0706.2001.930110.x

Baskin, S. I., Roberts, J., & Kendrick, Z. V. (1979). Effect of age on body weight, heart rate and blood pressure in pair-caged, male, Fischer 344 rats. AGE, 2(2), 47-50. https://doi.org/10.1007/bf02432256

Bronikowski, A. M. (2008). The evolution of aging phenotypes in snakes: a review and synthesis with new data. Age (Dordr), 30(2-3), 169-176. https://doi.org/10.1007/s11357-008-9060-5

Burrows, M. (2016). Development and deposition of resilin in energy stores for locust jumping. J Exp Biol, 219(Pt 16), 2449-2457. https://doi.org/10.1242/jeb.138941

Comelli, M., Meo, M., Cervantes, D. O., Pizzo, E., Plosker, A., Mohler, P. J., Hund, T. J., Jacobson, J. T., Meste, O., & Rota, M. (2020). Rhythm dynamics of the aging heart: an experimental study using conscious, restrained mice. Am J Physiol Heart Circ Physiol, 319(4), H893-H905. https://doi.org/10.1152/ajpheart.00379.2020

Doran, C. R., Estevez-Lao, T. Y., & Hillyer, J. F. (2017). Mosquito aging modulates the heart rate and the proportional directionality of heart contractions. J Insect Physiol, 101, 47-56. https://doi.org/10.1016/j.jinsphys.2017.06.013

Droogmans, S., Roosens, B., Cosyns, B., Hernot, S., Weytjens, C., Degaillier, C., Garbar, C., Caveliers, V., Pipeleers-Marichal, M., Franken, P. R., Bossuyt, A., Lahoutte, T., Schoors, D., & Van Camp, G. (2009). Echocardiographic and histological assessment of age-related valvular changes in normal rats. Ultrasound Med Biol, 35(4), 558-565. https://doi.org/10.1016/j.ultrasmedbio.2008.10.006

Grimes, K. M., Reddy, A. K., Lindsey, M. L., & Buffenstein, R. (2014). And the beat goes on: maintained cardiovascular function during aging in the longest-lived rodent, the naked mole-rat. Am J Physiol Heart Circ Physiol, 307(3), H284-291. https://doi.org/10.1152/ajpheart.00305.2014

Hofman, M. A. (1993). Encephalization and the evolution of longevity in mammals. Journal of Evolutionary Biology, 6(2), 209-227. https://doi.org/10.1046/j.1420-9101.1993.6020209.x

Holmes, D. J., Fluckiger, R., & Austad, S. N. (2001). Comparative biology of aging in birds: an update. Exp Gerontol, 36(4-6), 869-883. https://doi.org/10.1016/s0531-5565(00)00247-3

Kohn, J. C., Lampi, M. C., & Reinhart-King, C. A. (2015). Age-related vascular stiffening: causes and consequences. Front Genet, 6, 112. https://doi.org/10.3389/fgene.2015.00112

Lane, S. J., Frankino, W. A., Elekonich, M. M., & Roberts, S. P. (2014). The effects of age and lifetime flight behavior on flight capacity in Drosophila melanogaster. J Exp Biol, 217(Pt 9), 1437-1443. https://doi.org/10.1242/jeb.095646

McFarlane, J. E., & Fong, K. T. (1972). Differences in the effect of drugs on young and old hearts of the house cricket, Acheta domesticus (L.). Comp Gen Pharmacol, 3(11), 271-276. https://doi.org/10.1016/0010-4035(72)90003-1

Meneses, A., Castillo, C., Ibarra, M., & Hong, E. (1996). Effects of aging and hypertension on learning, memory, and activity in rats. Physiol Behav, 60(2), 341-345. https://www.ncbi.nlm.nih.gov/pubmed/8840889

Metcalfe, N. B., & Monaghan, P. (2003). Growth versus lifespan: perspectives from evolutionary ecology. Exp Gerontol, 38(9), 935-940. https://doi.org/10.1016/s0531-5565(03)00159-1

Mikula-Pietrasik, J., Pakula, M., Markowska, M., Uruski, P., Szczepaniak-Chichel, L., Tykarski, A., & Ksiazek, K. (2021). Nontraditional systems in aging research: an update. Cell Mol Life Sci, 78(4), 1275-1304. https://doi.org/10.1007/s00018-020-03658-w

Minias, P., & Podlaszczuk, P. (2017). Longevity is associated with relative brain size in birds. Ecology and Evolution, 7(10), 3558-3566. https://doi.org/10.1002/ece3.2961

O’Connor, T. P., Lee, A., Jarvis, J. U., & Buffenstein, R. (2002). Prolonged longevity in naked mole-rats: age-related changes in metabolism, body composition and gastrointestinal function. Comp Biochem Physiol A Mol Integr Physiol, 133(3), 835-842. https://doi.org/10.1016/s1095-6433(02)00198-8

Oh, J. K., Behmer, S. T., Marquess, R., Yegin, C., Scholar, E. A., & Akbulut, M. (2017). Structural, tribological, and mechanical properties of the hind leg joint of a jumping insect: Using katydids to inform bioinspired lubrication systems. Acta Biomater, 62, 284-292. https://doi.org/10.1016/j.actbio.2017.08.013

Olsson, M., & Shine, R. (2002). Growth to death in lizards. Evolution, 56(9), 1867-1870. https://doi.org/10.1111/j.0014-3820.2002.tb00202.x

Paternostro, G., Vignola, C., Bartsch, D. U., Omens, J. H., McCulloch, A. D., & Reed, J. C. (2001). Age-associated cardiac dysfunction in Drosophila melanogaster. Circ Res, 88(10), 1053-1058. https://doi.org/10.1161/hh1001.090857

Piiroinen, S., Lindstrom, L., & Lyytinen, A. (2010). Resting metabolic rate can vary with age independently from body mass changes in the Colorado potato beetle, Leptinotarsa decemlineata. J Insect Physiol, 56(3), 277-282. https://doi.org/10.1016/j.jinsphys.2009.10.015

Robert, K. A., Brunet-Rossinni, A., & Bronikowski, A. M. (2007). Testing the ‘free radical theory of aging’ hypothesis: physiological differences in long-lived and short-lived colubrid snakes. Aging Cell, 6(3), 395-404. https://doi.org/10.1111/j.1474-9726.2007.00287.x

Rockstein, M., & Miquel, J. (1973). Chapter 6 – AGING IN INSECTS. In M. Rockstein (Ed.), The Physiology of Insecta (Second Edition) (pp. 371-478). Academic Press. https://doi.org/https://doi.org/10.1016/B978-0-12-591601-1.50013-2

Stahl, M., Osmann, C., Ortmann, S., Kreuzer, M., Hatt, J. M., & Clauss, M. (2012). Energy intake for maintenance in a mammal with a low basal metabolism, the giant anteater (Myrmecophaga tridactyla). J Anim Physiol Anim Nutr (Berl), 96(5), 818-824. https://doi.org/10.1111/j.1439-0396.2011.01226.x