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.     

Breaking in a new function for casein kinase 2

DNA damage response mechanisms help ensure the fidelity of chromosomal transmission, and the failure of such mechanisms might lead to premature aging and cancer. A new report has established that casein kinase 2 (CK2), a protein that functions in diverse cellular processes, controls the activity of the DNA repair protein XRCC1. These results indicate that CK2 is a key participant in the cellular response to DNA damage.     

Lipid peroxidation and the aging process

Consistent evidence supports the hypothesis that a progressive accumulation of oxidative damage to important cellular molecules is a fundamental mechanism involved in most senescence-associated alterations. Oxidative damage occurs when free radicals produced within an organism are not completely destroyed by the appropriate endogenous defense systems. Because lipids are a major component of living organisms and probably the first easy target of free radicals once they are produced, lipid peroxidation might play an important role in initiating and/or mediating some aspects of the aging process. It has been widely demonstrated that there is an age-associated increase in the steady-state concentrations of lipid peroxidation products. However, establishing the involvement of this phenomenon in the pathogenesis of the aging process has not been an easy task. The recent development of more reliable techniques to measure lipid peroxidation, together with more well-defined animal models of aging, should be of great help in future studies in this field. The current evidence for the presence and importance of lipid peroxidation in the aging process is discussed in this review.     

Aging at the interface of stem cell renewal, apoptosis, senescence, and cancer

The aging-related research field has focused on the detection of genetic factors that affect the aging process, but more recently scientists have started to shift their attention to novel and more integrative ways of studying cellular and organismal function. Such approaches allow them to uncover and explore unexpected patterns and themes, resulting in a more comprehensive knowledge of the complex regulatory pathways and networks involved in aging and age-related diseases. Eventually, this knowledge will lead to a systems-level understanding of aging. The third "Functional Genomics of Aging" conference held in Palermo, Italy, in March/April 2006 highlighted some of the more exciting work in this area.     

Self-perception of aging and health among older adults in Korea

The way that each individual perceives his or her own aging and health may be a key indicator of adaptation and well-being in old age. This study explored the determinants of self-perception of aging and health using 291 community-dwelling older adults in Korea (mean AGE=69.9). Older individuals with lower levels of education and economic status and various types of health problems (more chronic conditions, greater disability, poorer vision, and greater numbers of sick days) were found to have more negative self-perception of aging and health. In addition, a significant role of psychological factors was observed. For self-perception of health, sense of mastery was found to be a significant factor, and for self-perception of aging, neuroticism was observed to be significant along with sense of mastery. The mediating role of self-perception of health was supported that positive perception of health intervened the adverse effects of health problems on self-perception of aging. The findings demonstrate the important roles of psychological resources and subjective perceptions and suggest a need to consider them when planning interventions.     

Ceramide, stress, and a "LAG" in aging

Recent studies have implicated the longevity assurance gene LAG1 in ceramide synthesis. In light of a role for ceramide in yeast and mammalian stress responses and mammalian cellular senescence, important connections are emerging between ceramide and organismal aging. In this Perspective, we examine the evidence for these connections in yeast, Drosophila, and mammals, and speculate on their implications.     

Experiences from Pagan women: A closer look at croning rituals

In this qualitative study I explore how Pagan women conceptualize aging, more specifically social aging, through the ritual process of being a Pagan and becoming a Crone. The central question of this research revolves around how older women who identify as Pagan experience, understand, and conceptualize their social aging and their role as aging women in American society. Semi-structured interviews were used to collect data and explore the meaning of aging for women identifying as Pagan. Major emergent themes within the data demonstrate that the croning ritual, a central aspect of Paganism, affirms these women in their process of aging. These women, through the ritual of croning, are able to understand their aging as celebration, maintain a positive sense of self while aging, and reclaim visibility as aging women. These women were able to embed their experiences of aging within a unique and specific cultural framework, a spiritual and foundational framework cultivating a spiritual connection with nature.     

The role of families in the population crisis

The population crisis in European countries can be synthesized into two phenomena: the loss of vitality and the aging society. What are the main consequences of this crisis? Can the family play a determining role in helping to face and overcoming these consequences? In this paper we suggest promoting the family as a possible means to help sustain or bring about a recovery in the demographic health of society. The first section is devoted to an analysis of the demographic decline across European countries by examining converging patterns in culturally, politically, and historically different contexts. The second section explores more deeply the interrelations between the determinants of the population crisis and living arrangements. A picture of the new shape of families across Europe precedes an analysis of the changing patterns in living arrangements and their link to reproductive functions. A final section studies the extent to which the family influences the role of women in the labor market.     

Aging in check

The spindle checkpoint monitors the interaction between spindle microtubules and kinetochores to prevent precocious entry into anaphase, delaying this stage of mitosis until all condensed chromosomes have been attached to the mitotic spindle in a bi-oriented manner (so that the two kinetochores associated with a pair of sister chromatids are oriented toward opposite poles of the spindle). In addition to conserved Bub and Mad family members, which are known to function in the spindle checkpoint pathway in organisms ranging from yeast to mammals, two mRNA transport genes, Rae1 and Nup9, are also involved in the spindle checkpoint function in mammals. Biochemically, activated spindle checkpoint components have been shown to suppress the activity of the anaphase promoting complex/cyclosome. It is generally thought that decreased activity of the checkpoint components predisposes cells to chromosomal instability, aneuploidy, and malignant transformation. Interestingly, a recent study has shed light on a new function of the spindle checkpoint components Bub3 and Rae1 in the regulation of aging. Mice with haploinsufficiency of Bub3 and Rae1 have a short life span that is associated with the early onset of aging-related features. The progeroid phenotypes caused by deficiency of Bub3 and Rae1 are tightly linked to precocious activation of cellular senescence, but not apoptotic, programs. Therefore, premature aging, rather than neoplastic transformation, may be the major manifestation of a compromised spindle checkpoint in vivo.     

The burden of pain on the shoulders of aging

More than 9% of the world population is older than 60. With age comes additional vulnerability to pain and the accumulation of insults that can engender ongoing misery. Insights into molecular and cellular aspects of pain might help escort people more comfortably into the senior ranks, but research that specifically addresses pain in the elderly is only now gearing up. Although a comprehensive understanding of how aging affects pain--and vice versa--is far off, experts report a good outlook for helping the millions of undertreated older people who experience pain on a daily basis.     

Oxidative mutagenesis, mismatch repair, and aging

A PubMed search for the term "oxidative stress" yields over 29,000 articles published on the subject over the past 10 years; more than 2000 of these articles also include the term "aging" in their title or abstract. Many theories of aging predict causal roles for oxidative stress in the myriad of pathological changes that occur as a function of age, including an increasing propensity to develop cancer. A possible link between aging and cancer is the induction and accumulation of somatic mutations caused by oxidative stress. This Review focuses on small mutational events that are induced by oxidative stress and the role of mismatch repair (MMR) in preventing their formation. It also discusses a possible inhibitory effect of oxidative stress on MMR. We speculate that a synergistic interaction between oxidative damage to DNA and reduced MMR levels will, in part, account for an accumulation of small mutational events, and hence cancer, with aging.     

Poly(ADP-ribosyl)ation, PARP, and aging

Poly(ADP-ribose) polymerases (PARPs) catalyze the poly(ADP-ribosyl)ation of proteins. This posttranslational modification, as generated by the DNA damage-activated enzymes PARP-1 and -2, has long been known to be involved in DNA repair. Correlative data have suggested an association between DNA damage-induced poly(ADP-ribosyl)ation and mammalian longevity, and this link has recently been strengthened by the discovery of interactions between PARP-1 and the Werner syndrome protein. Emerging additional members of the PARP family display different cellular localizations and are involved in diverse processes such as the regulation of telomere or centrosome function, thereby providing further, independent links between poly(ADP-ribosyl)ation and the aging process.     

Aging-related temporal constraints to stability and instability in postural control

In this study, we review the evidence that older adults tend to have both a shorter time to lose stability in the maintenance of standing posture and the functionally related but inverse problem of needing more time to reacquire stability in transitioning to a postural state. These age-related time limitations to processes of stability are hypothesized to enhance the probability of falling with aging and the problems that can occur in the transition between activities, such as sitting to standing and standing to walking. The potential role of fitness and health variables in mediating the temporal constraints on the acquisition and loss of postural stability in aging is discussed.     

The Educator as Advocate: The Gerontologist in an Academic Setting

The educator in a school of social work functions not only as a teacher of students but also as an advocate. The educator-advocate as gerontologist must simultaneously develop a core training in aging, induce other faculty members to add gerontological content, build interdisciplinary bridges with other academic units, and influence other educational institutions. The role of advocate demands a flexible use of strategies and tactics as well as evaluations of process and products, identification of factors associated with success and failure, and formulation of policy recommendations.     

The effects of religion on subjective aging in Singapore: An interreligious comparison

This interreligious comparison deals with Buddhist and Christian Chinese elderly Singaporeans. Based on the data gathered from in-depth interviews with five Buddhists and five Christians, this article explores how religion plays a role in the adjustment to the physical, social, and existential aging processes. It investigates the similarities and differences between Buddhist and Christian beliefs in terms of their effects on the subjective experience of aging. Findings indicate that religion can play an integrative role that facilitates adjustment to the aging process. Also, they suggest that though there are fundamental, irreducible differences in terms of religious beliefs and practices between Buddhism and Christianity, there are far less differences in the ways they impact on the integrative aging process. Some negative effects of religion on aging and some viewpoints about successful aging are presented in the discussion.     

Linking development and aging

Evolutionary theory predicts that the different life stages of organisms are coordinated to achieve maximal reproductive output. Moreover, aging can be seen as an evolutionary side effect of this selective process that applies to many living organisms. Hence, genetic, developmental, and physiological mechanisms resulting from this selection are expected to be conserved in diverse lineages. The insulin/insulin-like growth factor signaling (INS) pathway appears to be such a mechanism that regulates life span and reproduction in a variety of model organisms. Here I argue that the experimental tools of environmental manipulation and gene by environment interaction should be used more often both during the experimental organism's development and its adult life. This approach will help us to fully understand the functions of longevity-determining pathways and will determine the life stages during which these pathways exert their effects on adult life. These points are raised because of a recent Aging Cell publication by Tu and Tatar, in which the larval food environment was manipulated to determine the effects on adult reproduction, life span, aging, and INS. The results of this study are a promise of the usefulness of this approach for understanding the aging process.     

Using yeast to discover the fountain of youth

The budding yeast Saccharomyces cerevisiae has long served as a model organism for the study of basic cellular processes. Its short generation time, well-established molecular genetics, and fully sequenced genome have made this organism a favorite of researchers in diverse fields. Much of the information obtained has been shown to apply to higher eukaryotes, including humans. Recently, researchers have begun using yeast to tackle one of the outstanding questions in science: How and why do organisms age? The identification of individual genes in yeast that can affect the aging process itself has elevated this single-celled fungus to full contender status in the aging field. In this Perspective, we present two fundamentally different measures of aging in yeast: replicative life-span and stationary phase survival (chronological life-span). We describe the benefits and limitations of each and present models that attempt to explain these "aging" phenomena. Finally, we present compelling evidence that the use of yeast as a model system will ultimately prove beneficial to the study of human aging.     

Realities and Hopes for Older Gay Males

Abstract

Data about gay men in the Midwest over the age of 50 are extracted from a larger study of gay men and lesbian women. Information is sought regarding the role of sexual orientation, social networks, and social programs and activities in personal assessments of both the aging process and life satisfaction. The sample was divided into two groups: men 60 years of age and older, and men between the ages of 50 and 60. Differences were found between these subgroups, especially regarding acceptance of the aging process; yet these men were more similar than different in most aspects of life. Participation in gay community activities, social and religious, was found to be important for the quality of life of these men. Those integrated into the community, formally and informally, were also more likely to believe that their sexual orientation had helped their aging process.