This isssue of Journal of Anatomy contains review articles based on a Symposium held during a joint meeting of the Anatomical Society of Great Britain and Ireland, the Anatomical Society of South Africa and the Nederlandse Anatomen Vereniging on 15 April 1998 at Rolduc, The Netherlands. The Symposium has been edited by Professor Bernard Wood whose initial review constitutes an introduction to the succeeding articles.

The Symposium on ‘Mechanisms of Ageing and Longevity’ was held at the Royal Free Campus, Royal Free and University College Medical School, London, on 17 September 1999. It was organised and sponsored by the Anatomical Society of Great Britain and Northern Ireland with generous contributions from BBSRC, AgeNet and Research into Ageing.

The Symposium was organised as a result of recent discoveries in two principal areas: the genetics of longevity regulation in the nematode worm, Caenorhabditis elegans, and the cell biology of ageing in mammalian cells. Papers were presented covering the role of insulin-like signalling, free radical damage and caloric restriction in ageing of invertebrate and mammalian systems. One of the principal aims was to examine the idea that a genetically conserved signalling pathway might regulate ageing processes at both a cellular and an organismal level.

In the 19th century, several scientists attempted to relate bone trabecular morphology to its mechanical, load-bearing function. It was suggested that bone architecture was an answer to requirements of optimal stress transfer, pairing maximal strength to minimal weight, according to particular mathematical design rules. Using contemporary methods of analysis, stress transfer in bones was studied and compared with anatomical specimens, from which it was hypothesised that trabecular architecture is associated with stress trajectories. Others focused on the biological processes by which trabecular architectures are formed and on the question of how bone could maintain the relationship between external load and architecture in a variable functional environment. Wilhelm Roux introduced the principle of functional adaptation as a self- organising process based in the tissues. Julius Wolff, anatomist and orthopaedic surgeon, entwined these 3 issues in his book The Law of Bone Remodeling (translation), which set the stage for biomechanical research goals in our day. ‘Wolff's Law’ is a question rather than a law, asking for the requirements of structural optimisation. In this article, based on finite element analysis (FEA) results of stress transfer in bones, it is argued that it was the wrong question, putting us on the wrong foot. The maximal strength/minimal weight principle does not provide a rationale for architectural formation or adaptation; the similarity between trabecular orientation and stress trajectories is circumstantial, not causal. Based on computer simulations of bone remodelling as a regulatory process, governed by mechanical usage and orchestrated by osteocyte mechanosensitivity, it is shown that Roux's paradigm, conversely, is a realistic proposition. Put in a quantitative regulatory context, it can predict both trabecular formation and adaptation. Hence, trabecular architecture is not an answer to Wolff's question, in the sense of this article's title. There are no mathematical optimisation rules for bone architecture; there is just a biological regulatory process, producing a structure adapted to mechanical demands by the nature of its characteristics, adequate for evolutionary endurance. It is predicted that computer simulation of this process can help us to unravel its secrets.

This article illustrates how functional neuroimaging can be used to test the validity of neurological and cognitive models of language. Three models of language are described: the 19th Century neurological model which describes both the anatomy and cognitive components of auditory and visual word processing, and 2 20th Century cognitive models that are not constrained by anatomy but emphasise 2 different routes to reading that are not present in the neurological model. A series of functional imaging studies are then presented which show that, as predicted by the 19th Century neurologists, auditory and visual word repetition engage the left posterior superior temporal and posterior inferior frontal cortices. More specifically, the roles Wernicke and Broca assigned to these regions lie respectively in the posterior superior temporal sulcus and the anterior insula. In addition, a region in the left posterior inferior temporal cortex is activated for word retrieval, thereby providing a second route to reading, as predicted by the 20th Century cognitive models. This region and its function may have been missed by the 19th Century neurologists because selective damage is rare. The angular gyrus, previously linked to the visual word form system, is shown to be part of a distributed semantic system that can be accessed by objects and faces as well as speech. Other components of the semantic system include several regions in the inferior and middle temporal lobes. From these functional imaging results, a new anatomically constrained model of word processing is proposed which reconciles the anatomical ambitions of the 19th Century neurologists and the cognitive finesse of the 20th Century cognitive models. The review focuses on single word processing and does not attempt to discuss how words are combined to generate sentences or how several languages are learned and interchanged. Progress in unravelling these and other related issues will depend on the integration of behavioural, computational and neurophysiological approaches, including neuroimaging.

We have compared the distribution, numbers and volume of mucous glands in the tracheas of 11 mammalian species. No glands were present in the rabbit. The mouse only contained glands at the border between the trachea and larynx. In the rat, glands were commonest in the cephalad third of the trachea, but on average were much scarcer than in the larger species. Between species, there was a significant correlation between airway diameter and gland volume per unit surface area, suggesting that the rate of deposition of inhaled particles may increase in large airways. In the ventral portion of the trachea of about half the species, the glands were concentrated between the cartilaginous rings; in others they were evenly distributed over and between the rings. In most species in which the trachealis muscle attached to the internal surface of the cartilaginous rings, the glands were external to the muscle. In all species in which the muscle attached to the external surface of the cartilaginous rings, the glands were internal to the muscle. In the ox, goat, dog and sheep, the volume of glands per unit tracheal surface area was markedly greater in the ventral than the dorsal aspect of the trachea. The reverse was true of the pig. In humans, gland density in the 2 regions was similar. The frequency of gland openings was determined in the ox, goat, pig, dog and sheep tracheas, and ranged from 0.3 per mm2 in the dorsal portion of the sheep trachea to 1.5 per mm2 in the ventral portion of the ox trachea. For these 5 species, the volume of gland acini per unit luminal surface area varied linearly with the numbers of gland openings, with the volume of individual glands being constant at ∼ 120 nl.

Numerous theories of ageing have been proposed, and many have been tested experimentally, particularly using nematode models such as Caenorhabditis elegans. By combining those theories of ageing that remain plausible with recent findings from studies of C. elegans life span mutants, an integrated theory of ageing has been devised. This is formed from 3 interconnected elements: the evolutionary theory of ageing, the oxidative damage theory of ageing, and a nonadaptive programmed ageing theory. This tripartite theory of ageing gives rise to a number of predictions that may be tested experimentally.

Structural changes of the ventral velum of Xenopus laevis tadpoles from late prometamorphosis (stage 58) to the height of metamorphic climax (stage 62) were examined by light and transmission electron microscopy. Special emphasis was given to the blood vessel regression. Early changes of velar capillaries were formation of luminal and abluminal endothelial cell processes, vacuolation, and cytoplasmic and nuclear chromatin condensation. At the height of metamorphic climax, transmission electron microscopy revealed apoptotic endothelial cells with nuclear condensation and fragmentation, intraluminal bulging of rounded endothelial cells which narrowed or even plugged the capillary, and different stages of endothelial cell detachment (‘shedding’) into the vessel lumen. These changes explain the ‘miniaturisation’ of the velar microvascular bed as well as the typical features found in resin-casts of regressing velar vessels which have been observed in a previous scanning electron microscopy study of the ventral velum.

We rely on fossils for the interpretation of more than 95% of our evolutionary history. Fieldwork resulting in the recovery of fresh fossil evidence is an important component of reconstructing human evolutionary history, but advances can also be made by extracting additional evidence for the existing fossil record, and by improving the methods used to interpret the fossil evidence. This review shows how information from imaging and dental microstructure has contributed to improving our understanding of the hominin fossil record. It also surveys recent advances in the use of the fossil record for phylogenetic inference.

This review begins by setting out the context and the scope of human evolution. Several classes of evidence, morphological, molecular, and genetic, support a particularly close relationship between modern humans and the species within the genus Pan, the chimpanzee. Thus human evolution is the study of the lineage, or clade, comprising species more closely related to modern humans than to chimpanzees. Its stem species is the so-called ‘common hominin ancestor’, and its only extant member is Homo sapiens. This clade contains all the species more closely-related to modern humans than to any other living primate. Until recently, these species were all subsumed into a family, Hominidae, but this group is now more usually recognised as a tribe, the Hominini. The rest of the review sets out the formal nomenclature, history of discovery, and information about the characteristic morphology, and its behavioural implications, of the species presently included in the human clade. The taxa are considered within their assigned genera, beginning with the most primitive and finishing with Homo. Within genera, species are presented in order of geological age. The entries conclude with a list of the more important items of fossil evidence, and a summary of relevant taxonomic issues.

The structure and 3-dimensional pattern of the intraparenchymal microvessels in the brain of the lizard, Podarcis sicula, were studied by a combination of light and transmission electron microscopy as well as scanning electron microscopy of vascular corrosion casts. The angioarchitecture pattern consists of narrow hairpin-shaped microvascular loops of different length originating from the meningeal surface. In each loop, descending and ascending vessels are closely apposed to one another throughout their length and are connected by a narrow U-shaped terminal loop at their tips. The 2 limbs of the vessel pairs show a slightly different diameter but lack other structural differences. While some paired vessels give rise to a secondary hairpin-shaped loop with 2 possible branching patterns, there are no anastomotic intraparenchymal connections with analogous neighbouring structures. The cerebral vascular pattern of Podarcis sicula resembles that found in a few representatives of other vertebrate classes. All cerebral vessels structurally appear to be capillaries. Also the observations carried out on semithin and thin sections strongly support the capillary loop model in the Podarcis brain vasculature and, in accordance with studies carried out on various vertebrates, the general submicroscopic features of the brain capillary wall suggest the presence of an endothelial type blood-brain barrier.

Variations of the course of the internal carotid artery in the parapharyngeal space and their frequency were studied in order to determine possible risks for acute haemorrhage during pharyngeal surgery and traumatic events, as well as their possible relevance to cerebrovascular disease. The course of the internal carotid artery showed no curvature in 191 cases, but in 74 cases it had a medial, lateral or ventrocaudal curve, and 17 preparations showed kinking (12) or coiling (5) out of a total of 265 dissected carotid sheaths and 17 corrosion vascular casts. In 6 cases of kinking and 2 of coiling, the internal carotid artery was located in direct contact with the tonsillar fossa. No significant sex differences were found. Variations of the internal carotid artery leading to direct contact with the pharyngeal wall are likely to be of great clinical relevance in view of the large number of routine procedures performed. Whereas coiling is ascribed to embryological causes, curving is related to ageing and kinking is thought to be exacerbated by arteriosclerosis or fibromuscular dysplasia with advancing age and may therefore be of significance in relation to the occurrence of cerebrovascular symptoms.

Sublethal oxidative stresses increase the proportions of human fibroblasts positive for senescence associated β-galactosidase activity and accelerate the transition in the fibroblast morphotypes characterising fibroblast ageing. Stimulation of fibroblasts with TNF-α or IL-1α transiently increases the production of reactive oxygen species (ROS) in human fibroblasts. Here we propose that repeated stimulation of WI-38 fibroblasts with TNF-α or IL-1α can generate enough ROS to accelerate the transition in the fibroblast morphotypes and increase the proportion of cells positive for senescence associated β-galactosidase activity. The involvement of ROS is suggested by experiments where the stimulation of fibroblasts with TNF-α or IL-1α are performed in the presence of N-acetylcysteine which increases the intracellular antioxidant potential. It is proposed that the decrease in the proportions of morphotypes I and II, and the increase in the proportions of morphotypes III to VI observed after successive stimulation with TNF-α or IL1-α is attributed to an increased ROS production occurring during the stimulation.

The lacrimal sac and nasolacrimal duct are surrounded by a wide cavernous system of veins and arteries comparable to a cavernous body. The present study aimed to demonstrate the ultrastructure of the nervous tissue and the localisation of neuropeptides involved in the innervation of the cavernous body, a topic not previously investigated. Different S-100 protein antisera, neuronal markers (neuron-specific enolase, anti- 200 kDa neurofilament), neuropeptides (substance P, neuropeptide Y, calcitonin gene-related peptide, vasoactive intestinal polypeptide) and the neuronal enzyme tyrosine hydroxylase were used to demonstrate the distribution pattern of the nervous tissue. The ultrastructure of the innervating nerve fibres was also examined by means of standard transmission electron microscopy.

The cavernous body contained specialised arteries and veins known as barrier arteries, capacitance veins, and throttle veins. Perivascularly, the tissue was rich in myelinated and unmyelinated nerve fibres in a plexus-like network. Small seromucous glands found in the region of the fundus of the lacrimal sac were contacted by nerve fibres forming a plexus around their alveoli. Many nerve fibres were positive for S-100 protein (S 100), neuron-specific enolase (NSE), anti-200 kDa neurofilament (RT 97), calcitonin gene-related peptide (CGRP), substance P (SP), tyrosine hydroxylase (TH), and neuropeptide Y (NPY). Vasoactive intestinal polypeptide (VIP) immunoreactivity was only demonstrated adjacent to the seromucous glands.

Both the density of nerve fibres as well as the presence of various neuropeptides emphasises the neural control of the cavernous body of the human efferent tear ducts. By means of this innervation, the specialised blood vessels permit regulation of blood flow by opening and closing the lumen of the lacrimal passage as effected by the engorgement and subsidence of the cavernous body, at the same time regulating tear outflow. Related functions such as a role in the occurrence of epiphora related to emotional responses are relevant. Moreover, malfunction in the innervation of the cavernous body may lead to disturbances in the tear outflow cycle, ocular congestion or total occlusion of the lacrimal passages.

This paper reviews the application of medical imaging and associated computer graphics techniques to the study of human evolutionary history, with an emphasis on basic concepts and on the advantages and limitations of each method. Following a short discussion of plain film radiography and pluridirectional tomography, the principles of computed tomography (CT) and magnetic resonance imaging (MRI) and their role in the investigation of extant and fossil morphology are considered in more detail. The second half of the paper deals with techniques of 3-dimensional visualisation based on CT and MRI and with quantitative analysis of digital images.

Skeletal muscle has the unique ability to increase the rate of oxygen usage during contraction. This has led several workers to suggest that by-products of this increased oxygen consumption, oxygen-derived free radicals, may be primarily responsible for exercise-induced damage to skeletal muscle. However, because of this rapidly changing redox state, skeletal muscle has developed a number of different endogenous mechanisms which adapt rapidly following a period of exercise. These include numerous structural and biochemical changes such as increased muscle activity of antioxidant enzymes and content of stress or heat shock proteins (HSPs). This adaptation is associated with protection against the potentially damaging effects of a second period of exercise. In addition, we have recently demonstrated a significant increase in free radical production during a period of nondamaging exercise, which is rapidly followed by a significant increase in the expression of antioxidant enzymes and HSPs, suggesting that a change in redox state of the muscle may act as signal for adaptation.

Bell-Magendie's law of separation of spinal function states that afferent and efferent fibres join the spinal cord separately in ventral and dorsal spinal nerve roots. For over 100 years there have been reports that challenge the exclusiveness of this law in mammals; very few studies have referred to man. We conducted a prospective morphological study in patients with preganglionic traction injuries of the brachial plexus to address this question. Avulsed ventral and dorsal roots were examined after variable intervals from the injury for histological and ultrastructural evidence for myelinated afferent fibres entering the cord via the ventral roots. Intact myelinated fibres were found in all ventral root specimens, but the majority of fibres in later biopsies are regenerative. A small number of fibres could be demonstrated that are likely to be ‘wrong way ventral afferents’. Their number is falsely low due to wallerian degeneration of dorsal and ventral afferents following the mechanical and ischaemic effects of traction injury. Our findings are the first morphological evidence in human material that Bell-Magendie's law might not entirely be correct and they underline the difficulties in comparing traumatic with experimental rhizotomy.

Teeth preserve a record of the way they grow in the form of incremental markings in enamel, dentine and cementum. These make it possible to reconstruct cellular activity and the timing of dental development in living and fossil primates, including hominids. They also provide a way of exploring the mechanisms that underlie morphological change during evolution and the nature of the relationship between ontogeny and phylogeny. All living great apes are dentally mature by about 11 y, irrespective of their body mass. While the early period of root formation in living great apes is shorter than in modern humans, enamel takes approximately the same time to form, irrespective of how thick it is. In general, differences in the total time taken to form enamel seem not to be due to differences in the rate at which enamel and dentine are secreted, but rather to faster or slower rates of differentiation of ameloblasts and odontoblasts and therefore to the number of secretory cells active at any one time during tooth formation. Tooth size, especially height, may influence the sequence of appearance of tooth mineralisation stages. The space available in the jaws may also have an influence on both the timing of tooth bud/crypt appearance and the sequence of gingival emergence. When each of these potential influences on dental development are carefully considered, and incremental markings used to calibrate key events, the developing dentition can provide an estimate of the period of dental maturation in fossil hominoids. However, the influence of body mass on the period of dental development among primates remains unclear. The earliest hominoids, dated at around 18 Mya, may still have had modern monkey-like maturational profiles, and the earliest hominids, dated between 1.8 and 3.7 Mya, modern great ape-like maturational profiles. Exactly when the extended or prolonged modern human-like maturational profile first appeared remains debatable, but the most secure suggestion might be at the time of the appearance of the earliest archaic Homo sapiens, when brain size and body mass were finally both within the ranges known for modern humans. But at present we should not reject the hypothesis that an extended, modern human-like, maturational profile arose more than once during human evolution in parallel with an increase in brain size.

The mouse thymus changes dramatically during pregnancy. It shrinks in size, and the cortex is extensively reduced from midpregnancy onwards. Despite this, there is surprisingly little evidence for any increase in apoptosis, and considerable evidence that mitosis of thymocytes continues throughout pregnancy. In spite of overall involution the thymic medulla actually expands in midpregnancy due to a combination of mitosis of epithelial cells and an accumulation of lymphocytes. The extent and nature of these changes are examined in this study at the ultrastructural level. The epithelial cells of the subcapsular cortex (type 1 cells) become wrinkled and exhibit powers of phagocytosis, whilst the other cortical epithelial cells are relatively unchanged, although the formation of epithelial/thymocyte rosettes and thymic nurse cells is more clearly seen in midpregnancy than usual. Other changes associated with pregnancy involve the medullary epithelial cells that undergo an increased level of mitosis. Their greater numbers surround accumulations of lymphocytes to form the characteristic medullary epithelial rings. Cell movement through blood vessel walls was clearly observed in midpregnancy, but not at other times. Interdigitating cells in the medulla become more conspicuous as pregnancy proceeds and the cells become phagocytic. The endoplasmic reticulum in plasma cells becomes expanded, indicating increased secretory activity. These results highlight the active nature of the thymus in pregnancy in spite of its involution. This picture contradicts the conventional notion that an involuted thymus is inactive.

Age-associated neurodegenerative diseases such as Alzheimer's disease are characterised by neuronal impairment that leads to cognitive deficits. As certain affected neurons depend on trophic factors such as neurotrophins (NTs), impairment in NT function has been suggested to be a component of neuronal damage associated with such disorders. Age-related neurodegenerative diseases are also characterised by high levels of proinflammatory cytokines such as tumour necrosis factor alpha (TNFα) in the CNS. Because TNFα receptors and certain NT receptors share a high degree of homology and are capable of activating similar signalling pathways, one possibility is that altered cytokine levels may affect NT function in the aged or diseased CNS. Here we wish briefly to review the evidence suggesting a role for cytokine and NT in the onset of age-associated neurodegenerative diseases. We propose that cytokine/NT interactions may alter neuronal homeostasis, thus possibly contributing to some of the neuronal degeneration occurring during such age-associated CNS diseases.

The alginate bead culture system has been utilised by several groups to examine the in vitro proteoglycan (PG) metabolism of chondrocytes and intervertebral disc cells, but the nature of the PGs produced has not been examined in detail. This is largely due to the difficulty of separating the anionically charged sodium alginate support matrix from PGs which are similarly charged. In the present study ovine annulus fibrosus, transitional zone and nucleus pulposus cells were dissociated enzymatically from their respective matrices by sequential digestion with pronase/clostridial collagenase and DNAase and then cultured in alginate beads for 10 d. The beads were solubilised and subjected to DEAE Sepharose CL6B anion exchange chromatography to separate the sodium alginate bead support matrix material quantitatively from the disc cell PGs. The alginate free bead PGs were then subjected to composite agarose polyacrylamide gel electrophoresis to resolve PG populations and the PGs were transferred to nitrocellulose membranes by semidry electroblotting. The PGs were identified by probing the blots with a panel of antibodies to defined PG core protein and glycosaminoglycan side chain epitopes. Alginate beads of disc cells were also embedded in paraffin wax and 4μm sections cut to immunolocalise decorin, biglycan, versican, and the 7-D-4 PG epitope within the beads. Decorin and biglycan had similar distributions in the beads, being localised on the cell surface whereas versican and the 7-D-4 PG epitope were immunolocalised interterritoriarly. This study is the first to demonstrate that ovine disc cells synthesise versican in alginate bead culture. Furthermore the immunoblotting studies also showed that a proportion of the 7-D-4 PG epitope was colocalised with versican.