A synthesis of senescence predictions for indeterminate growth, and support from multiple tests in wild lake trout

Senescence—the deterioration of functionality with age—varies widely across taxa in pattern and rate. Insights into why and how this variation occurs are hindered by the predominance of laboratory-focused research on short-lived model species with determinate growth. We synthesize evolutionary theories of senescence, highlight key information gaps and clarify predictions for species with low mortality and variable degrees of indeterminate growth. Lake trout are an ideal species to evaluate predictions in the wild. We monitored individual males from two populations (1976–2017) longitudinally for changes in adult mortality (actuarial senescence) and body condition (proxy for energy balance). A cross-sectional approach (2017) compared young (ages 4–10 years) and old (18–37 years) adults for (i) phenotypic performance in body condition, and semen quality—which is related to fertility under sperm competition (reproductive senescence)—and (ii) relative telomere length (potential proxy for cellular senescence). Adult growth in these particular populations is constrained by a simplified foodweb, and our data support predictions of negligible senescence when maximum size is only slightly larger than maturation size. Negative senescence (aka reverse senescence) may occur in other lake trout populations where diet shifts allow maximum sizes to greatly exceed maturation size.

DNA methylation clocks tick in naked mole rats but queens age more slowly than nonbreeders

Naked mole rats (NMRs) live an exceptionally long life, appear not to exhibit age-related decline in physiological capacity and are resistant to age-related diseases. However, it has been unknown whether NMRs also evade aging according to a primary hallmark of aging: epigenetic changes. To address this question, we profiled n = 385 samples from 11 tissue types at loci that are highly conserved between mammalian species using a custom array (HorvathMammalMethylChip40). We observed strong epigenetic aging effects and developed seven highly accurate epigenetic clocks for several tissues (pan-tissue, blood, kidney, liver, skin clocks) and two dual-species (human–NMR) clocks. The skin clock correctly estimated induced pluripotent stem cells derived from NMR fibroblasts to be of prenatal age. The NMR epigenetic clocks revealed that breeding NMR queens age more slowly than nonbreeders, a feature that is also observed in some eusocial insects. Our results show that despite a phenotype of negligible senescence, the NMR ages epigenetically.

The damage-independent evolution of ageing by selective destruction

Ageing is currently believed to reflect the accumulation of molecular damage due to energetic costs of maintenance, as proposed in disposable soma theory (DST). Here we have used agent-based modelling to describe an alternative theory by which ageing could undergo positive selection independent of energetic costs. We suggest that the selective advantage of fast-growing mutants might necessitate a mechanism of counterselection we name selective destruction, which removes the faster growing cells from the tissue, preventing the threat of morbidity and mortality they pose. As a result, the survival advantage would shift to the slower cells, allowing them to spread, inducing ageing in the form of a metabolic slowdown. Selective destruction could therefore provide a proximal cause of ageing that is both consistent with the gene expression hallmarks of ageing, and independent of accumulating damage. If true, negligible senescence would acquire a new meaning of increased basal mortality.

A synthesis of senescence predictions for indeterminate growth, and support from multiple tests in wild lake trout

Senescence, or the deterioration of functionality with age, varies widely across taxa in pattern and rate. Insights into why and how this variation occurs are hindered by the predominance of lab-focused research on short-lived model species with determinate growth. We synthesize evolutionary theories of senescence, highlight key information gaps, and clarify predictions for species with low mortality and variable degrees of indeterminate growth. Lake trout are an ideal species to evaluate predictions in the wild. We monitored individual males from two populations (1976-2017) longitudinally for changes in adult mortality (actuarial senescence) and body condition (proxy for energy balance). A cross-sectional approach (2017) compared young (ages 4-10 years) and old (18-37 years) adults for (1) phenotypic performance in body condition, and semen quality - which is related to fertility under sperm competition (reproductive senescence), and (2) relative telomere length (potential proxy for cellular senescence). Adult growth in these particular populations is constrained by a simplified food web, and our data support predictions of negligible senescence when maximum size is only slightly larger than maturation size. Negative senescence (aka reverse senescence) may occur in other lake trout populations where diet shifts allow maximum sizes to be much larger than maturation size.

Salamander Insights Into Ageing and Rejuvenation

Exhibiting extreme regenerative abilities which extend to complex organs and entire limbs, salamanders have long served as research models for understanding the basis of vertebrate regeneration. Yet these organisms display additional noteworthy traits, namely extraordinary longevity, indefinite regenerative potential and apparent lack of traditional signs of age-related decay or “negligible senescence.” Here, I examine existing studies addressing these features, highlight outstanding questions, and argue that salamanders constitute valuable models for addressing the nature of organismal senescence and the interplay between regeneration and ageing.

No evidence of physiological declines with age in an extremely long-lived fish

Although the pace of senescence varies considerably, the physiological systems that contribute to different patterns of senescence are not well understood, especially in long-lived vertebrates. Long-lived bony fish (i.e., Class Osteichthyes) are a particularly useful model for studies of senescence because they can readily be aged and exhibit some of the longest lifespans among vertebrates. In this study we examined the potential relationship between age and multiple physiological systems including: stress levels, immune function, and telomere length in individuals ranging in age from 2 to 99 years old in bigmouth buffalo (Ictiobus cyprinellus), the oldest known freshwater teleost fish. Contrary to expectation, we did not find any evidence for age-related declines in these physiological systems. Instead, older fish appeared to be less stressed and had greater immunity than younger fish, suggesting age-related improvements rather than declines in these systems. There was no significant effect of age on telomeres, but individuals that may be more stressed had shorter telomeres. Taken together, these findings suggest that bigmouth buffalo exhibit negligible senescence in multiple physiological systems despite living for nearly a century.