Developing a research agenda in biogerontology: physiological systems

The Biology of Aging Program (BAP) at the National Institute on Aging supports research in many areas, including processes of cell senescence and apoptosis, genetic influences on aging, and how aging leads to tissue dysfunction. Several approaches to research on aging physiological systems are described, along with BAP programmatic efforts to enhance and support that research. Understanding the relation between aging and tissue dysfunction has led to new insights into how health can be improved for aged individuals.     

Mitigating the tithonus error: genetic analysis of mortality phenotypes

Summarizing an organism's age at death in terms of the mean or maximum life-span is the most popular way to describe genetic effects on aging. In this Perspective, the author describes a new study with the fly Drosophila melanogaster, in which another type of measure is also used: the age-dependent risk of death, or age-specific mortality. Changes in age-specific mortality reflect the underlying physiological deterioration of an organism as it ages. Thus, the author argues that these changes provide a phenotype that is ideal for the genetic analysis of aging.     

Medicalizing the optimal: Anti-aging medicine and the quandary of intervention

The emergence of anti-aging medicine over the past two decades has posed tremendous challenges for traditional categories that define the relationship between aging and biomedicine. The frameworks of nature and disease have been critical in marking how biomedicine can and should intervene. Anti-aging advocates posit that because aging is a predictable, biological universal, it is natural and can therefore be understandable. Moreover, proponents accept and perpetuate the pervasive construction that aging is a painful decline. Here, its undesirability coupled with its knowability render the process of aging ameliorable. Thus, anti-aging advocates argue that aging is natural, not a disease, but should nonetheless serve as a site of intervention. Situating the optimization of the aging process as their primary goal, many anti-aging advocates assert that it is more emblematic of human nature to liberate the body from its perceived biological constraints than it is natural to age.     

Unearthing Loci that influence life span

It is known that certain hormones are involved in determining longevity (for example, insulin and insulin-like growth factor). Results presented in a paper published in this week's issue of Science allow us to add steroid hormones to this list. Anne Simon and colleagues show for the first time that a sterol hormone--ecdysone of the fly Drosophila melanogaster--regulates life span. In this Perspective, I discuss the implications of this result in the context of gene regulation and mechanisms of aging.     

The quest for a general theory of aging and longevity

Extensive studies of phenomena related to aging have produced many diverse findings, which require a general theoretical framework to be organized into a comprehensive body of knowledge. As demonstrated by the success of evolutionary theories of aging, quite general theoretical considerations can be very useful when applied to research on aging. In this theoretical study, we attempt to gain insight into aging by applying a general theory of systems failure known as reliability theory. Considerations of this theory lead to the following conclusions: (i) Redundancy is a concept of crucial importance for understanding aging, particularly the systemic nature of aging. Systems that are redundant in numbers of irreplaceable elements deteriorate (that is, age) over time, even if they are built of elements that do not themselves age. (ii) An apparent aging rate or expression of aging is higher for systems that have higher levels of redundancy. (iii) Redundancy exhaustion over the life course explains a number of observations about mortality, including mortality convergence at later life (when death rates are becoming relatively similar at advanced ages for different populations of the same species) as well as late-life mortality deceleration, leveling off, and mortality plateaus. (iv) Living organisms apparently contain a high load of initial damage from the early stages of development, and therefore their life span and aging patterns may be sensitive to early-life conditions that determine this initial damage load. Thus, the reliability theory provides a parsimonious explanation for many important aging-related phenomena and suggests a number of interesting testable predictions. We therefore suggest adding the reliability theory to the arsenal of methodological approaches applied to research on aging.     

Population aging and long-term care policies in the Gulf region: a case study of Oman

Population aging is a phenomenon occurring across the globe including in countries traditionally exhibiting population dividends and “youth bulges.” The Gulf Corporation Council countries are no exception as they currently experience a process of population aging, albeit at a different stage from many developed countries. However, due to historically high fertility rates and fast-paced epidemiological transition, some of these countries will experience population aging at a higher pace than what has been observed in Europe and the United States. This article reviews recent developments in long-term care policies in the Gulf region with a focus on Oman as an example of a high-income Arab country that is experiencing population aging while still being governed by traditional family aged-care norms. Utilizing existing data and published research complemented by policy analysis and field visits, we analyze the process of population aging in Oman and neighboring countries and its policy implications.     

Aging cartilage and osteoarthritis--what's the link?

Cartilage aging can contribute to the development of osteoarthritis (OA), the most common cause of chronic pain and disability in older adults. Articular cartilage is a unique tissue from the perspective of aging in that the cells (chondrocytes) and the majority of the extracellular matrix proteins experience little turnover, resulting in a tissue that must withstand years of use and can also accumulate years of aging-associated changes. Accumulation of advanced glycation end products (AGEs) occurs in cartilage, and the potential role of AGEs in the development of OA is being investigated. An age-associated reduction in growth factor signaling and an increase in oxidative stress may also play an important role in the age-OA connection. Further elucidation of mechanisms that affect chondrocyte function with aging should lead to novel interventions designed to slow the aging process in cartilage with the goal of preventing age-associated OA.     

Aging research grows up

Long viewed as an insoluble enigma, aging is shedding its cloak of mystery as scientists start to understand why and how we age. Many studies support the theoretical argument that aging occurs because natural selection weakens with age, leaving us vulnerable to harmful, late-acting genes. As for what causes aging, scientists have narrowed the pack of candidates to a handful, including free radicals and reactions between glucose and proteins. In recent decades, many mechanisms for lengthening life in animals have come to light. By extending this research, scientists may be closing in on ways to lengthen the human life-span.     

The reinterpretation of finitude: An introduction to three articles on the philosophy of aging

Whereas the expected problems of population aging are discussed extensively in the mass media, with a strong emphasis on the costs of pensions and care in the future, philosophy has remained virtually silent about the many aspects of aging and gerontology relevant to the discipline. However, aging is not a new topic in philosophy; it only has to be reintroduced. Although the three authors offer different perspectives on aging, there is a common effort to reinterpret the fundamental experience of finitude in the light of aging.     

Natural neighborhood networks — Important social networks in the lives of older adults aging in place

Neighborhoods are important places of aging and meaningful contexts of life for many older people. The overall aim of this study was to explore the public life of older people aging in place in order to understand neighborhoods as the material places where public life occurs, networks as the social places of public life, and to examine how these neighborhoods and networks influence the experience of aging and wellbeing. Adopting a friendly visiting methodology, data was collected over an 8-month period using participant observation, visual methods and an innovative interview technique called the “go along method”. Data were analyzed using grounded theory and a coding strategy that integrated textual, visual, and auditory data. Results provide insights into the micro-territorial functioning of neighborhoods and highlight third places and transitory zones as significant sites for older residents. Embedded within these places is a natural neighborhood network — a web of informal relationships and interactions that enhance well being and shape the everyday social world of older adults aging in place.     

Harvard Crooners: Building Intergenerational Relationships Through Participatory Music Making

The world is rapidly aging, and yet aging is fraught with many difficulties. In particular, the rights of older people to participate fully in cultural life are frequently not met. To help address this issue, we propose an innovative model for intergenerational, participatory music-making between younger people and older people. Specifically, instead of giving traditional, non-participatory performances for older people as is commonly done in nursing homes and other elderly institutions, we advocate for engaging seniors in collective music-making and singing. We believe this kind of collective music-making will better meet the rights of older adults to participate in cultural life and will lead to stronger intergenerational relationships.     

Autophagy and aging--when "all you can eat" is yourself

A recent paper provides evidence that macroautophagy is an essential downstream pathway for one of the mutations known to extend life span. Autophagy, or the degradation of intracellular components by the lysosomal system, was thought for a long time to be a catabolic process responsible for cellular cleanup. However, in recent years, we have learned that autophagy comes in different sizes and shapes, macroautophagy being one of them, and that this cellular maid plays many more roles than previously anticipated. Activation of autophagy is essential in physiological processes as diverse as morphogenesis, cellular differentiation, tissue remodeling, and cellular defense, among others. Furthermore, its participation in different pathological conditions, including cancer and neurodegeneration, is presently a subject of intense investigation. A role in aging has now been added to this growing list of autophagy functions. The activity of different forms of autophagy decreases with age, and this reduced function has been blamed for the accumulation of damaged proteins in old organisms. Research such as that covered in this Perspective shows that there is much more than trash to worry about when autophagy is not functioning properly.     

Come one, come all

Aging is a complex process that involves the gradual functional decline of many different tissues and cells. Gene expression microarray analysis provides a comprehensive view of the gene expression signature associated with age and is particularly valuable for understanding the molecular mechanisms that contribute to the aging process. However, because of the stochastic nature of the aging process, animals of the same chronological age often manifest great physiological differences. Therefore, profiling the gene expression pattern of a large population of aging animals risks either exaggerating or masking the changes in gene expression that correspond to physiological aging. In a recent paper, Golden and Melov surveyed the gene expression profiles of individual aging Caenorhabditis elegans, hoping to circumvent the problem of variability among worms of the same chronological age. This initial analysis of age-dependent gene expression in individual aging worms is an important step toward deciphering the molecular basis of physiological aging.     

More than a sum of our cells

Cells in the body grow and die, cells in lab dishes grow and die, and individual organisms grow and die. The parallels seem maddeningly obvious, but scores of scientists still labor to draw the correct connections, to uncover the mechanisms that underlie aging in cell culture flasks and in whole animals. Do our cells stop growing, quit working, cease dividing, or start dying as we age? Do we die when our cells do, or are we somehow more than the sum of our cells? For decades, scientists have searched for evidence that links changes in cell growth, cell function, cell division, and cell death to the phenomenon we call aging. Although definitive proof eludes them, researchers continue to conduct experiments in tissue culture and in animal models, amassing information that points us toward a greater understanding of what aging is--and is not.     

The age of cancer

The biggest risk factor for cancer isn't smoking or bad diet or anything a person can avoid. It's growing old. New findings might help explain the connection between aging and cancer. According to the study, a gene that's faulty in a disorder that resembles accelerated aging shuts down in many cancers.     

GenPhilly: A Strategy for Improving the Sustainability of Aging in Community Initiatives

GenPhilly is an innovative, replicable model that was developed in Philadelphia, Pennsylvania, to inspire and engage emerging leaders from a variety of disciplines to promote and sustain an aging-in-community agenda. Administrative support is provided by the Area Agency on Aging, Philadelphia Corporation for Aging, yet it was designed by its members to be peer-led. In this way, young professionals in their 20s and 30s can capitalize on popular culture to create unique professional development opportunities and get younger generations thinking about the type of city in which they themselves want to get older. The group has benefited the field of aging by building awareness of aging services in the wider community; facilitating cross-disciplinary learning and innovation around aging issues; stressing the competitive advantage for emerging leaders from all fields to know about aging issues; strengthening the aging network workforce; breaking down stereotypes about working with older adults; and introducing expertise from outside the aging network to benefit older adults. Encouraging the development of similar groups will not only benefit the field of aging, it will assist the next generation of leaders in many fields to plan better for their communities and for themselves.     

Urine-concentrating ability in the aging kidney

Urine-concentrating ability is decreased in the aging mammalian kidney. Studies have revealed various changes in kidney function that occur with aging and may explain the reduced ability to concentrate urine. Recently, the genes encoding many of the water- and solute-transport proteins and the vasopressin receptor, all of which are involved in urine concentration, have been cloned. Therefore, the molecular mechanisms that cause the reduction in urine-concentrating ability with aging can now be deciphered. In this Perspective, I discuss recent experiments designed to characterize this change in kidney function in aging mammals.     

Innovative models of aging in place: Transforming our communities for an aging population

As the proportion of the global population over 60 continues to grow, the issue of where and how elders are going to live becomes increasingly pressing. The idea or “aging in place” – in which elders remain in their own homes and communities – is becoming an increasingly popular alternative to age-segregated retirement communities. This article documents three new models of aging in place – naturally occurring retirement communities (NORC-SSPs), villages and campus-affiliated communities – and explores how they seek to provide both services and meaningful connections among members. Data from interviews and site visits reveal both promising practices as well as challenges such as how to ensure access for low and moderate-income elders, integrating elders from diverse cultural and linguistic back grounds, and building the leadership and participation of elders. By looking critically at these models, the author argues that many previously held theories and assumptions about the aging process and social capital formation must be reexamined in light of the agency of elders and the new organizational models. Ultimately the design of our communities – both physically and socially – and our approach to retirement must be restructured to support the needs of an aging population.