Biological clocks as age estimation markers in animals: a systematic review and meta-analysis

Various biological attributes associated with individual fitness in animals change predictably over the lifespan of an organism. Therefore, the study of animal ecology and the work of conservationists frequently relies upon the ability to assign animals to functionally relevant age classes to model population fitness. Several approaches have been applied to determining individual age and, while these methods have proved useful, they are not without limitations and often lack standardisation or are only applicable to specific species. For these reasons, scientists have explored the potential use of biological clocks towards creating a universal age-determination method. Two biological clocks, tooth layer annulation and otolith layering have found universal appeal. Both methods are highly invasive and most appropriate for post-mortem age-at-death estimation. More recently, attributes of cellular ageing previously explored in humans have been adapted to studying ageing in animals for the use of less-invasive molecular methods for determining age. Here, we review two such methods, assessment of methylation and telomere length, describing (i) what they are, (ii) how they change with age, and providing (iii) a summary and meta-analysis of studies that have explored their utility in animal age determination. We found that both attributes have been studied across multiple vertebrate classes, however, telomere studies were used before methylation studies and telomere length has been modelled in nearly twice as many studies. Telomere length studies included in the review often related changes to stress responses and illustrated that telomere length is sensitive to environmental and social stressors and, in the absence of repair mechanisms such as telomerase or alternative lengthening modes, lacks the ability to recover. Methylation studies, however, while also detecting sensitivity to stressors and toxins, illustrated the ability to recover from such stresses after a period of accelerated ageing, likely due to constitutive expression or reactivation of repair enzymes such as DNA methyl transferases. We also found that both studied attributes have parentally heritable features, but the mode of inheritance differs among taxa and may relate to heterogamy. Our meta-analysis included more than 40 species in common for methylation and telomere length, although both analyses included at least 60 age-estimation models. We found that methylation outperforms telomere length in terms of predictive power evidenced from effect sizes (more than double that observed for telomeres) and smaller prediction intervals. Both methods produced age correlation models using similar sample sizes and were able to classify individuals into young, middle, or old age classes with high accuracy. Our review and meta-analysis illustrate that both methods are well suited to studying age in animals and do not suffer significantly from variation due to differences in the lifespan of the species, genome size, karyotype, or tissue type but rather that quantitative method, patterns of inheritance, and environmental factors should be the main considerations. Thus, provided that complex factors affecting the measured trait can be accounted for, both methylation and telomere length are promising targets to develop as biomarkers for age determination in animals.     

Individual tooth macrowear pattern guides the reconstruction of Sts 52 (Australopithecus africanus) dental arches

The functional restoration of the occlusal relationship between maxillary and mandibular tooth rows is a major challenge in modern dentistry and maxillofacial surgery. Similar technical challenges are present in paleoanthropology when considering fragmented and deformed mandibular and maxillary fossils. Sts 52, an Australopithecus africanus specimen from Sterkfontein Member 4, represents a typical case where the original shape of the dental arches is no longer preserved. It includes a partial lower face (Sts 52a) and a fragmented mandible (Sts 52b), both incomplete and damaged to such an extent to thwart attempts at matching upper and lower dentitions. We show how the preserved macrowear pattern of the tooth crowns can be used to functionally reconstruct Sts 52's dental arches. High‐resolutiondental stone casts of Sts 52 maxillary and mandibular dentition were mounted and repositioned in a dental articulator. The occlusal relationship between antagonists was restored based on the analysis of the occlusal wear pattern of each preserved tooth, considering all dental contact movements represented in the occlusal compass. The reconstructed dental arches were three‐dimensional surface scanned and their occlusal kinematics tested in a simulation. The outcome of this contribution is the first functional restoration of A. africanus dental arches providing new morphometric data for specimen Sts 52. It is noteworthy that the method described in this case study might be applied to several other fossilspecimens. Am J Phys Anthropol, 2013. © 2013 Wiley Periodicals, Inc.     

Derivation of the short form of the Oral Health Impact Profile in Spanish (OHIP-EE-14)

doi: 10.1111/j.1741‐2358.2012.00613.x
Derivation of the short form of the Oral Health Impact Profile in Spanish (OHIP‐EE‐14) Background and Objective: The Oral Health Impact Profile is the most frequently used and validated of the Oral Health Quality of Life instruments. Several short versions have been developed; and a validation of the OHIP‐49 in Spanish has been published. The objective was to develop the short version of the Oral Health Impact Profile in Spanish (OHIP‐EE‐14). Methods: Cross‐sectional study. One hundred and thirty‐one persons aged ≥60 years attending a social centre for the elderly, residents of a nursing home and persons seeking dental care at a dental school in Mexico City were interviewed and examined. The validity of each of the 49 questions was evaluated, and, to construct the short version, 14 items were selected. The perceived need for dental treatment, number of teeth, presence of coronal caries, root caries, presence of dental plaque and utilisation of removable prosthesis were measured. Internal consistency, repeatability and discriminant validity were calculated. Results: The OHIP‐EE‐14 was reliable (Cronbach’s‐α = 0.918, ICC = 0.825). Significant associations were found between OHIP‐EE‐14 and the number of teeth and perceived need for dental treatment. Conclusions: The OHIP‐EE‐14 is a reliable and valid instrument and can be used in subjects aged 60 years and over from Mexico City.     

The choice of the femoral center of rotation affects material loss in total knee replacement wear testing – A parametric finite element study of ISO 14243-3

A leading cause of long-term failure of total knee replacements (TKRs) is osteolysis caused by polyethylene wear particles. The current gold standard for preclinical wear testing of TKRs is mechanical knee simulators. The definition of the femoral center of flexion-extension rotation (CoR) has been identified as one possible source of variability within TKR wear tests, since the femoral curvature varies from distal to posterior. The magnitude of the influence on wear due to changes in location of femoral CoR has not been investigated in depth. During this study, a computational framework utilizing finite element analysis for modelling wear of TKRs was developed and used to investigate the influence of the location of femoral CoR on TKR polyethylene wear during standardized displacement controlled testing (ISO 14243-3:2014). The study was carried out using a 40-point Latin Hypercube Design of Experiments approach. Volumetric wear was highly correlated to femoral CoR in both the superior/inferior and anterior/posterior directions, with a stronger relationship in the superior/inferior direction. In addition, wear scars showing linear penetration were examined, with large differences in simulations at the extreme ends of the sampling region. In this study, it was found that variations in the location of the femoral center of rotation can represent a large source of variability in the preclinical testing and evaluation of the wear performance of total knee replacements. This study represents the first attempt at quantifying the effect on wear of different femoral center of rotations across a large sampling space.     

Variation in occlusal dental wear of two Chalcolithic populations in the southern Levant

Occlusal wear rate and wear plane in two Chalcolithic ( approximately 6500-5500 BP) samples from the southern Levant were compared, using paired first and second mandibular molars. Though food staples in both societies were derived from agro-pastoralism, they were located in distinct environmental regions: Wadi (W.) Makkukh in the Judean desert, and Peqi'in in the Upper Galilee. Accordingly, it was predicted that variation in wear should occur due to their location in distinct environments. Jaw size and tooth size were measured to estimate the possible impact of these variables on wear scores. Molar occlusal surfaces were divided into four quadrants, and wear scores were recorded for each quadrant. Principal axis analysis was then performed between total wear scores of paired, adjacent first and second molars to assess wear rates. Principal axis analysis was also used to analyze the change in occlusal wear plane in each sample by comparing between-buccal-cusps wear scores of the first molar with lingual wear scores of the second molar. The results indicate that the occlusal wear plane was similar in both samples but that wear tended to be more rapid in W. Makkukh. Since both samples were similar in jaw/tooth size, it is argued that the results reflect less refined food-processing methods as well as the unintentional ingestion of sand by individuals interred in the Judean desert.     

Radula formation in two species of Conoidea (Gastropoda)

The radula is the basic feeding structure in gastropod molluscs and exhibits great morphological diversity that reflects the exceptional anatomical and ecological diversity occurring in these animals. This uniquely molluscan structure is formed in the blind end of the radular sac by specialized cells (membranoblasts and odontoblasts). Secretion type, and the number and shape of the odontoblasts that form each tooth characterize the mode of radula formation. These characteristics vary in different groups of gastropods. Elucidation of this diversity is key to identifying the main patterns of radula formation in Gastropoda. Of particular interest would be a phylogenetically closely related group that is characterized by high variability of the radula. One such group is the large monophyletic superfamily Conoidea, the radula of which is highly variable and may consist of the radular membrane with five teeth per row, or the radular membrane with only two or three teeth per row, or even just two harpoon-like teeth per row without a radular membrane. We studied the radulae of two species of Conoidea (Clavus maestratii Kilburn, Fedosov & Kantor, 2014 [Drilliidae] and, Lophiotoma acuta (Perry, 1811) [Turridae]) using light and electron microscopy. Based on these data and previous studies, we identify the general patterns of the radula formation for all Conoidea: the dorsolateral position of two groups of odontoblasts, uniform size, and shape of odontoblasts, folding of the radula in the radular sac regardless of the radula configuration. The morphology of the subradular epithelium is most likely adaptive to the radula type.     

Technical note: Applicability of tooth cementum annulation to an archaeological population

The use of tooth cementum annulations for age determination has been deemed promising, exhibiting high correlations with chronological age. Despite its apparent potential, to date, the tooth cementum annulations method has been used rarely for estimating ages in archaeological populations. Here we examine the readability of cementum annulations and the consistency of age estimates using a sample of 116 adults from the Iron Gates Gorge Mesolithic/Neolithic series. Our examination of the method pointed to several sources of error that call into question the use of this method for estimating the chronological ages of archaeologically derived dental samples. The poor performance of the method in our analysis might be explained by taphonomic influences, including the effect of chemical and biological agents on dental microstructures. Am J Phys Anthropol 2009. © 2009 Wiley‐Liss, Inc.     

A ‘conovenomic’ analysis of the milked venom from the mollusk-hunting cone snail Conus textile—The pharmacological importance of post-translational modifications

Cone snail venoms provide a largely untapped source of novel peptide drug leads. To enhance the discovery phase, a detailed comparative proteomic analysis was undertaken on milked venom from the mollusk-hunting cone snail, Conus textile, from three different geographic locations (Hawai’i, American Samoa and Australia's Great Barrier Reef). A novel milked venom conopeptide rich in post-translational modifications was discovered, characterized and named α-conotoxin TxIC. We assign this conopeptide to the 4/7 α-conotoxin family based on the peptide's sequence homology and cDNA pre-propeptide alignment. Pharmacologically, α-conotoxin TxIC demonstrates minimal activity on human acetylcholine receptor models (100 μM, <5% inhibition), compared to its high paralytic potency in invertebrates, PD₅₀ = 34.2 nMol kg⁻¹. The non-post-translationally modified form, [Pro]^2,8[Glu]¹⁶α-conotoxin TxIC, demonstrates differential selectivity for the α3β2 isoform of the nicotinic acetylcholine receptor with maximal inhibition of 96% and an observed IC₅₀ of 5.4 ± 0.5 μM. Interestingly its comparative PD₅₀ (3.6 μMol kg⁻¹) in invertebrates was ∼100 fold more than that of the native peptide. Differentiating α-conotoxin TxIC from other α-conotoxins is the high degree of post-translational modification (44% of residues). This includes the incorporation of γ-carboxyglutamic acid, two moieties of 4-trans hydroxyproline, two disulfide bond linkages, and C-terminal amidation. These findings expand upon the known chemical diversity of α-conotoxins and illustrate a potential driver of toxin phyla-selectivity within Conus.