In lieu of an abstract, here is a brief excerpt of the content:Alzheimer's Disease, Mild Cognitive Impairment, and the Biology of Intrinsic AgingThomas B. L. Kirkwood (bio)Keywordsaging, Alzheimer’s disease, genetic mutation, mild cognitive impairment, telomereThe article by Gaines and Whitehouse (2006) raises key questions about the uncertain relationship between (i) the intrinsic, "normal" aging process, and (ii) the clinicopathologic states represented by the labels of Alzheimer's disease (AD) and mild cognitive impairment (MCI). This short commentary offers a perspective on (...) this debate that is drawn from a consideration of underlying biological mechanisms.Because age is unquestionably the greatest single risk factor associated with AD and MCI, I begin by asking what we know about the intrinsic processes of aging. The central feature of current understanding of intrinsic aging is that it consists of the gradual, lifelong accumulation of a wide variety of molecular and cellular faults that begins very early in life and eventually leads to overt functional impairments resulting in age-related frailty, disability, and disease (Kirkwood 2005). This is an essentially bottom-up process. A strong consensus has emerged in recent years that there is no active program for aging and that there are no genetic factors that have evolved specifically to cause aging or age-related diseases. Unquestionably, there are genes that influence susceptibility to disease and even length of life, but these genes are genes for maintenance and repair functions, not for aging. It is the limitation in the past evolutionary pressure to invest in greater longevity than was required, within an environment where life was usually truncated by hazards such as starvation, injury, or infection, that means that our maintenance systems—good as they are—are insufficient to keep us going indefinitely. Added to this is the idea that there are probably also genes that program processes that are good for the young organism, but which may in later life have harmful effects. Processes like inflammation and apoptosis, which are seen to occur extensively in aged tissues, including brain, surely evolved to help cope with infection and cellular damage arising earlier in life. That they are called into play in aged tissues is a direct, but secondary, consequence of accumulated damage.With this general framework to understand the intrinsic biology of aging, let us now ask what we might expect a priori for the aging of an organ such [End Page 79] as the brain. Although we cannot pretend complete ignorance of how the brain actually does age, our enquiry can be based entirely on data from other organ systems, so we can develop our predictions about brain aging without prejudice.Aging begins very early during human development, faults accumulating from the first stages of embryonic development. Each time a cell divides, each of the daughter cells is likely to acquire a few new mutations. We know this from the estimates for the error rate in DNA replication and the size of the human genome. It is confirmed by direct evidence that at individual gene loci where mutations have been measured, mutation frequency increases with age (Morley 1998; Vijg 2000). In addition to replication errors, DNA is damaged on a daily basis to a very considerable degree by agents such as reactive oxygen species (free radicals), which are formed as byproducts of normal cellular metabolism. Although most of this damage is corrected by repair, the repair mechanisms themselves are not error free and additional mutations accumulate through this route. If a mutation is lethal to the cell, the cell dies and thus the mutation is eliminated. However, the majority of mutations are nonlethal, either because the mutation is recessive and the cell carries an intact gene copy on the other chromosome, because the gene is not currently required, or because the mutation produces only a delayed deleterious effect. Examples of genes that produce delayed deleterious effects include the genes responsible for familial AD. It is interesting to reflect that on statistical grounds alone, it is almost certain that each of us carries a randomly determined fraction of cells in our brains that bear amyloid precursor protein or presenilin mutations associated with AD. We also carry a heterogeneous array of random mutations that compromise essential cell maintenance functions. How many such... (shrink)

A recent report by Tyner et al.1 suggests that p53 is bad for longevity. Heterozygotic mice carrying a p53 mutation that apparently enhances the stability of the wild‐type protein showed shorter lifespans and faster ageing while also developing fewer tumours. This fits with the idea that cellular ageing is the price paid for better protection against unlimited proliferation of cancer cells. But other work shows that there is a strong positive association between DNA repair‐mediated protection against cancer and ageing. So (...) what are we to make of the new data with regard to overall understanding of the mechanisms of ageing? BioEssays 24:577–579, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Human life expectancy has increased dramatically through improvements in public health, housing, nutrition and general living standards. Lifespan is now limited chiefly by intrinsic senescence and its associated frailty and diseases. Understanding the biological basis of the ageing process is a major scientific challenge that will require integration of molecular, cellular, genetic and physiological approaches. This article reviews progress that has been made to date, particularly with regard to the genetic contribution to senescence and longevity, and assesses the scale of (...) the task that remains. (shrink)

The prelims comprise: Introduction Genetic Architecture of the Life Span Genetics of Longevity Genetics and the Future of Old Age Conclusion.

Objectives: To explore how subjects in a placebo-controlled vitamin A supplementation trial among Ghanaian women aged 15–45 years perceive the trial and whether they know that not all trial capsules are the same, and to identify factors associated with this knowledge.Methods: 60 semistructured interviews and 12 focus groups were conducted to explore subjects’ perceptions of the trial. Steps were taken to address areas of low comprehension, including retraining fieldworkers. 1971 trial subjects were randomly selected for a survey measuring their knowledge (...) that not all trial capsules are the same. The subjects’ fieldworkers were also interviewed about their characteristics and trial knowledge. Factors associated with knowledge were explored using multi-level modeling.Results: Although subjects knew they were taking part in research, most thought they were receiving an active and beneficial medication. Variables associated with knowledge were education and district of residence. Radio broadcasts benefited those with some schooling. Fieldworkers’ characteristics were not associated with subjects’ knowledge.Conclusions: Research and debate on new or improved consent procedures are urgently required, particularly for subjects with little education. (shrink)

Mitochondrial dysfunction has long been considered a key mechanism in the ageing process but surprisingly little attention has been paid to the impact of mitochondrial number or density within cells. Recent reports suggest a positive association between mitochondrial density, energy homeostasis and longevity. However, mitochondrial number also determines the number of sites generating reactive oxygen species (ROS) and we suggest that the links between mitochondrial density and ageing are more complex, potentially acting in both directions. The idea that increased density, (...) especially when combined with mitochondrial dysfunction, might accelerate ageing is supported by a negative correlation between mitochondrial density and maximum longevity in an interspecies comparison in mammals, and by evidence for an intimate interconnection between cellular ROS levels, mitochondrial density and cellular ageing. Recent data suggest that retrograde response, which activates mitochondrial biogenesis, accompanies cellular ageing processes. We hypothesise that increased mitochondrial biogenesis, and possibly also impaired degradation and segregation of mitochondria, if occurring as adaptation to pre‐existing mitochondrial dysfunction, might aggravate ROS production and thus actively contribute to ageing. BioEssays 29:908–917, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Wearable robots are an emerging form of technology that allow organizations to combine the strength, precision, and performance of machines with the flexibility, intelligence, and problem-solving abilities of human wearers. Active exoskeletons are a type of wearable robot that gives wearers the ability to effortlessly lift up to 200 lbs., as well as perform other types of physically demanding tasks that would be too strenuous for most humans. Synchronization between exoskeleton suits and wearers is one of the most challenging requirements (...) to operate these technologies effectively. In this conceptual paper, we extend interpersonal adaption theory (IAT) to the exoskeleton context and explicate (a) the antecedents that are most likely to shape synchrony in human-exoskeleton interactions, (b) automatic and strategic synchrony as adaptive behaviors in human-exoskeleton interactions, and (c) outcome variables that are especially important in these processes. Lastly, we offer a discussion of key methodological challenges for measuring synchrony in human-exoskeleton interactions and offer a future research agenda for this important area. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:LaudatioTimothy B. Noone (bio)On Sunday, July 26, 2009, the Franciscan Institute was pleased to award to Dr. Girard J. Etzkorn its 22nd Franciscan Institute Medal in recognition of a lifetime of scholarship, editing and publication of texts on medieval philosophy and theology, with a special emphasis on the Franciscan intellectual tradition. The ceremony was held in the Trustees Room of Doyle Hall on the campus of St. Bonaventure University (...) and attended by over 100 scholars, students, friends and members of Dr. Etzkorn's extended families. The award ceremony began with a personal appreciation by Dr. Thomas Shannon, Ph.D., emeritus of the Worcester Polytechnic Institute (Worcester, MA), former member during the 1960s with Dr. Etzkorn of the Sacred Heart Province of Friars Minor (St. Louis, MO). It was followed by the formal laudatio of the honorée presented by former colleague and friend, Dr. Timothy B. Noone, Ph.D., of the Catholic University of America, the text of which is printed here. The event concluded with personal remarks by Dr. Etzkorn on his life as a scholar of the Franciscan tradition."Let us praise men of renown and our fathers in their generation." Sirach 44:1The wisdom of Sirach, the last of the Solomonic books of the Old Testament, would seem an appropriate place to begin this evening's festivities. No doubt, Gerry is squirming a bit in his chair, thinking in his customary humility that the words of Sirach are a bit too high for him. But we must learn to acknowledge what is true and great wherever it is, even when (or to put the matter correctly, especially when) the truth and greatness are found in ourselves. So there will be [End Page 259] no holding back on the present occasion, since the text from Sirach points out our path.We should start with a brief sketch of Gerry's life. Born in Kirkwood, Missouri in 1927, Gerry received his primary and secondary education in Missouri before attending the University of Dayton in the fall of 1944. After three semesters studying chemical engineering, he was drafted into the military, serving in the U.S. Army as part of the occupation forces of Japan after the surrender of August, 1945. This seeming irrelevancy actually became quite important in Gerry's life, for it was during his service in Japan that he encountered the Franciscans and decided to enter the Order after returning to the U.S. Once he had completed his degrees in philosophy and theology and been ordained, Gerry was sent to the University of Louvain, where he took his doctorate, producing a thesis that contained a partial edition of Roger Marston's hitherto unpublished Quodlibetal questions.This work at Louvain presaged in many ways the bulk of Gerry's work: he edited and studied a Franciscan medieval text from Latin manuscripts and studied its philosophical and theological doctrines. After returning from Louvain, Gerry taught for ten years at Quincy College and Seminary before leaving the Franciscans in 1971. But the Franciscans and he were far from being through with each other. Within two years Gerry arrived here to work with Fr. Gedeon Gàl on the Ockham Edition, then in the throes of its labors. Initially working as an Associate Editor on the Ockham Edition, Gerry eventually became Chief Editor of the Scotus Project, the successor project at the Institute to the Ockham Edition.During his twenty-two years at the Institute, Gerry kept up a steady pace of editions, some connected with the Institute's research projects and others springing from his own interests. Among the former, we must note three volumes of the Opera theologica of Ockham and four volumes of the Opera philosophica of Scotus; among the latter, we find the complete edition of Roger Marston's Quodlibetal questions, the edition of John Peckham's Quodlibetal questions, numerous articles containing briefer editions of lesser figures, and a volume of manuscript descriptions, analyzing manuscripts never before described in the Vatican Library. [End Page 260]What I have mentioned so far would be enough for any one human being within the scope of one lifetime. But God had more in store for Gerry... (shrink)

The present account, based on introspective comments, deals with motivation and hedonic tone as subjective factors which affect continuous work at high speeds. Actual introspective reports are given. The earlier papers in the series described the experimental procedure and presented objective data.

How good is psychotherapy as a tool of research into human nature? There is an orthodox defence of it as a research tool, which relies on showing that interpretations are true of the patient when they satisfy certain criteria. This defence is examined and rejected. The reply is considered that an interpretation which 'keeps things moving' is true, or an approximation to the truth. This reply is rejected by comparing and contrasting an interpretation in psychotherapy with one from brainwashing sessions. (...) Two suppositions about psychotherapy (which weaken its discovery powers) are deliberately adopted — the suppositions that the material produced is 'perspective' and 'method' dependent. An unorthodox defence of psychotherapy is then offered — by means of a watery sense of 'discover'. This enables us to outline a weak sense in which psychotherapy is a valid enterprise, but one which is still strong enough for research purposes. (shrink)

Lectures delivered under the auspices of the University of Poona.