The evolution of aging phenotypes in snakes: a review and synthesis with new data

Reptiles are underutilized vertebrate models in the study of the evolution and persistence of senescence. Their unique physiology, indeterminate growth, and increasing fecundity across the adult female lifespan motivate the study of how physiology at the mechanistic level, life history at the organismal level, and natural selection at the evolutionary timescale define lifespan in this diverse taxonomic group. Reviewed here are, first, comparative results of cellular metabolic studies conducted across a range of colubrid snake species with variable lifespan. New results on the efficiency of DNA repair in these species are synthesized with the cellular studies. Second, detailed studies of the ecology, life history, and cellular physiology are reviewed for one colubrid species with either short or long lifespan (Thamnophis elegans). New results on the rate of telomere shortening with age in this species are synthesized with previous research. The comparative and intraspecific studies both yield results that species with longer lifespans have underlying cellular physiologies support the free-radical/repair mechanistic hypothesis for aging. As well, both underscore the importance of mortality environment for the evolution of aging rate.     

The menopause transition and the aging process: a population perspective

The menopause transition period, extending from active reproductive capacity with well-characterized hormone profiles through reproductive senescence, has been less well studied than any other period of the life span except extreme old age. Yet, for the gerontologist, this is an important period to understand for at least two reasons. First, during this period changes in the neuroendocrine system and ovary may provide a model for the study of other aging-related processes. Second, specific characteristics of this transitional period (including duration, intensity, and age at menopause) may be considered "aging", and influence short-term health and quality-of-life status, as well as life expectancy. In addition to discussing the menopause transition in terms of age and culture, we include some of the theories and conceptual models that can influence the nature and interpretation of information from this time period, and its ultimate impact on health and health practice.     

Neuroendocrine-immune interactions: a theoretical approach to aging

Among the systemic theories of aging, both a 'nervous-neuroendocrine' and an 'immune' hypothesis have been proposed. The discovery of the complex interactions working among the neuroendocrine and the immune systems suggests the revision of the systemic theories of aging, particularly in the light of the recent evidence that some age-associated alterations in the neuroendocrine and in the immune systems are mutually interdependent even at very old age, as revealed by the fact that experimental manipulation of one of the two systems modifies and sometimes restores the function of the other one. These findings clearly demonstrate that at least some of the age-related alterations of the nervous, neuroendocrine and immune networks are not per se intrinsic and irreversible and that the definition of the temporal priority in the age-related deterioration is rather is rather difficult to be assigned to one or other homeostatic apparatuses. As an alternative to pure, either 'neuroendocrine' or 'immune', theories of aging, it has been hypothesized that, due to the strict interactions existing among the nervous, neuroendocrine and immune systems during the whole life of the organism, it is the disruption of such interactions in old age which is responsible for most of the age-associated dysfunctions (Fabris, 1986). This theoretical approach is discussed in the light of a stochastic or single-cause oriented hypothesis of aging.     

Cell aging in vitro: a historical perspective

This article describes the historical background to the demonstration by Hayflick and Moorhead that human diploid cell strains in culture have limited life-spans. I suggest that the recognition of cell aging in vitro is an example from the biological sciences of a Kuhnian scientific revolution.     

The evolution of mammalian aging

The incidence of aging is different between mammals and their closer ancestors (e.g. reptiles and amphibians). While all studied mammals express a well-defined aging phenotype, many amphibians and reptiles fail to show signs of aging. In addition, mammalian species show great similarities in their aging phenotype, suggesting that a common origin might be at work. The proposed hypothesis is that mammalian aging evolved together with the ancestry of modern mammals. In turn, this suggests that the fundamental cause of human aging is common to most, if not all, mammals and might be a unique phenomenon. Experimental procedures capable of testing these theories and how to map the causes of mammalian and thus, human aging, are predicted.     

Bridging the treatment gap: the secondary care perspective

Protocols and integrated care pathways can be valuable in the hospital care of patients with heart failure or left ventricular systolic dysfunction after acute myocardial infarction. A designated member of staff, often a specialist nurse, must be responsible for identifying patients suitable for management by the protocol and for ensuring that the protocol is adhered to. A new training scheme for "limited echocardiography" might enable specialist nurses to investigate left ventricular function within the first 24 hours of admission. Patients should be discharged from hospital as soon as they are out of danger. At present, they are often kept in hospital for process reasons. A "continuing care" clinic run by a specialist nurse, where patients can be seen daily after discharge until they are stabilised, is one way of bridging the gap between secondary and primary care. Communication between secondary and primary care needs to improve and same day discharge summaries are essential.     

Mechanical factors in arterial aging: a clinical perspective

The human arterial system in youth is beautifully designed for its role of receiving spurts of blood from the left ventricle and distributing this as steady flow through peripheral capillaries. Central to such design is "tuning" of the heart to arterial tree; this minimizes aortic pressure fluctuations and confines flow pulsations to the larger arteries. With aging, repetitive pulsations (some 30 million/year) cause fatigue and fracture of elastin lamellae of central arteries, causing them to stiffen (and dilate), so that reflections return earlier to the heart; in consequence, aortic systolic pressure rises, diastolic pressure falls, and pulsations of flow extend further into smaller vessels of vasodilated organs (notably the brain and kidney). Stiffening leads to increased left ventricular (LV) load with hypertrophy, decreased capacity for myocardial perfusion, and increased stresses on small arterial vessels, particularly of brain and kidney. Clinical manifestations are a result of diastolic LV dysfunction with dyspnea, predisposition to angina, and heart failure, and small vessel degeneration in brain and kidney with intellectual deterioration and renal failure. While aortic stiffening is the principal cause of cardiovascular disease with age in persons who escape atherosclerotic complications, it is not a specific target for therapy. The principal target is the smooth muscle in distributing arteries, whose relaxation has little effect on peripheral resistance but causes substantial reduction in the magnitude of wave reflection. Such relaxation is achieved through regular exercise and with the vasodilating drugs that are used in modern treatment of hypertension and cardiac failure.     

Bridging the treatment gap: the primary care perspective

The Darlington heart failure service model, part of the South Durham Heart Failure Network, was devised to overcome barriers to accurate diagnosis and effective management of heart failure. It involves rapid diagnosis of left ventricular systolic dysfunction (LVSD) and ongoing heart failure management. A weekly one stop diagnostic clinic, run by a general practitioner (GP) specialist and a heart failure nurse, is jointly funded by the primary care trust and the South Durham NHS Trust. If LVSD is confirmed, a management plan is formulated which includes patient education and initiation of evidence based treatment. The heart failure nursing service is invaluable in bridging the gap between primary and secondary care. Local guidelines, together with continuing education of GPs and practice nurses, and the new General Medical Services contract, should further increase the uptake of evidence based treatments at target doses.     

Mechanical factors in arterial aging: a clinical perspective.

The human arterial system in youth is beautifully designed for its role of receiving spurts of blood from the left ventricle and distributing this as steady flow through peripheral capillaries. Central to such design is "tuning" of the heart to arterial tree; this minimizes aortic pressure fluctuations and confines flow pulsations to the larger arteries. With aging, repetitive pulsations (some 30 million/year) cause fatigue and fracture of elastin lamellae of central arteries, causing them to stiffen (and dilate), so that reflections return earlier to the heart; in consequence, aortic systolic pressure rises, diastolic pressure falls, and pulsations of flow extend further into smaller vessels of vasodilated organs (notably the brain and kidney). Stiffening leads to increased left ventricular (LV) load with hypertrophy, decreased capacity for myocardial perfusion, and increased stresses on small arterial vessels, particularly of brain and kidney. Clinical manifestations are a result of diastolic LV dysfunction with dyspnea, predisposition to angina, and heart failure, and small vessel degeneration in brain and kidney with intellectual deterioration and renal failure. While aortic stiffening is the principal cause of cardiovascular disease with age in persons who escape atherosclerotic complications, it is not a specific target for therapy. The principal target is the smooth muscle in distributing arteries, whose relaxation has little effect on peripheral resistance but causes substantial reduction in the magnitude of wave reflection. Such relaxation is achieved through regular exercise and with the vasodilating drugs that are used in modern treatment of hypertension and cardiac failure.     

Songbirds: A novel perspective on estrogens and the aging brain

Songbirds perform some remarkable feats of memory, including forming memories for songs and for complex spatial features of their environments. Research into the neural and hormonal control of these behaviors reveals discrete circuits that can retain considerable plasticity in adulthood. The songbird brain is also a prominent site of estrogen synthesis and a target of estrogen action. Estrogens contribute to the plasticity of the adult songbird brain and contribute to the bird's capacity to form and retrieve some memories. We describe the brain, behavior and endocrinology of songbirds and discuss these findings within the context of the neurology of the aging brain.     

The experimental evolution of aging in fruitflies

—The evolutionary theory of aging suggests that the level of repair will evolve to an intermediate optimum that permits the accumulation of random damage to cells. This, in turn, causes a decline in essential functions during the life span of an organism. The central claim of the life history theory of aging is that intrinsic mortality rates evolve in response to changes in extrinsic mortality rates. To prove this central claim, it must be evaluated experimentally. Experimental evolution is an approach that has been yielding interesting results from both a variety of questions posed and organisms examined. In this article the organism chosen for study is the fruitfly (Drosophilia melanogaster) in which the evolutionary effects of high and low adult mortality rates are compared. It has been found that higher extrinsic mortality rates lead to the evolution of higher intrinsic mortality rates and a shorter life span. This is the first clear experimental demonstration of the central claim of the evolutionary theory of aging.     

A perspective: the new millennium dawns on a new paradigm for cardiology--molecular genetics

Western civilization had two great epochs--the sixth century B.C. and the 18th century. The 21st century is likely to be the third great epoch. Although cardiology has advanced more in the last 50 years than in the previous 2,000, it is likely to advance more in the next two or three decades than in the previous 2,000 years, including those 50 golden years. The engines of ingenuity to provide the thrust for the 21th century will come from molecular genetics and the application of recombinant deoxyribonucleic acid (DNA) techniques. Identification of all human genes (50,000 to 100,000) in the next two to three years will help link thousands of etiologies and risk factors with their respective diseases, which represents a new paradigm in medicine. This is illustrated by the implications to be drawn from familial hypertrophic cardiomyopathy and the 50 new genes already identified to be responsible for cardiac disease. The hope for prevention and treatment of human disease is unprecedented. Twenty diseases account for 80% of the deaths in the Western world and are due to 100 to 200 genes, all of which will be available in a couple of years. The Phoenician alphabet (inclusive of the Greek vowels) of 26 letters launched two millenniums of Western civilization, whereas the DNA alphabet of only four letters will launch and dominate the next millennium.     

The new world of aging

H.E. Julia T. de Alvarez is Ambassador, Alternate Representative for the Dominican Republic’s Permanent Mission to the United Nations. Ambassador Alvarez is a leading international advocate for the rights of the elderly and has been an articulate spokesperson for the need to develop programs which empower the elderly especially in developing countries. She was instrumental in the approval by the U.N. General Assembly of the “United Nations Principles for Older Persons.”     

Cognitive aging: activity patterns and maintenance intentions

This study examined relationships between cognitive functioning in older people and (1) levels of mental, physical and social activities, and (2) intentions regarding maintenance of cognitive functioning. Participants (N=145) were 70-91 years of age, varied in health status and socio-economic backgrounds. Current cognitive functioning was assessed by psychometric tests and real world problem solving tasks. Crystallized ability was indexed by the National Adult Reading Test (NART). Degree of involvement in mentally demanding activities was positively related to a fluid cognitive factor after effects of age, prior functioning, gender, health, and socio-economic status were accounted for. Social and physical activities were not related to the cognitive measures. Age effects on cognitive functioning were reduced among participants who reported undertaking activities intentionally to maintain cognitive functioning.