Mouse and human cells versus oxygen

Mice and humans are at opposite ends of the mammalian spectrum of longevity. A major question in biology is whether this difference can be accounted for by differences in the properties of cells from these two species. A new publication from Judith Campisi's lab reports that human cells in culture are more resistant than mouse cells to the damaging effects of 20% oxygen. The greater burden of DNA damage sustained by mouse cells causes them to rapidly enter a phase of culture in which most cells enter permanent growth arrest (replicative senescence). However, some mouse cells usually escape from senescence and then grow into an immortal cell line. This never happens in human fibroblast cell cultures. Human cells also eventually enter replicative senescence in culture, but this phenomenon is caused by shortening of telomeres and not by DNA damage of the type responsible for mouse cell senescence. Human fibroblasts never spontaneously escape from senescence. This Perspective reviews differences between mouse and human cells that could account for these differences in behavior. Some evidence indicates that human cells are generally more resistant than mouse cells to oxidative damage to DNA, but more needs to be done to confirm this finding and to understand the underlying mechanisms. Whether or not there are differences in the amount of DNA damage caused by oxygen or in the early phase of repair, there may be important differences in the later consequences of DNA damage. Mouse cells appear to be able to continue to divide with DNA damage that has not been repaired or has been misrepaired, and becomes fixed in the form of chromosomal abnormalities. The checkpoints that cause cells to stop dividing when chromosomes develop abnormalities (aberrations or shortened telomeres) appear to operate more efficiently in human cells. Much more work is needed to understand the basis for these differences and the implications for aging and cancer.     

Vitamin B1 blocks damage caused by hyperglycemia

Diabetes accelerates the aging process and leads to complications that include blindness, renal failure, nerve damage, stroke, and cardiovascular disease. It has been hypothesized that high plasma glucose concentrations are responsible for increased mitochondrial free radical production and subsequent inactivation of glyceraldehyde phosphate dehydrogenase (GAPDH) in vascular endothelial cells and other cells implicated in these complications. As a result of the decreased ability of GAPDH to process upstream metabolites, three pathways of metabolic damage are activated, which include the advanced glycation end-product formation pathway, the protein kinase C pathway, and the hexosamine pathway. All three pathways have been implicated in abnormal cell signaling in diabetes. A group of German and U.S. scientists has now found that treating diabetic rats with high doses of benfotiamine, a lipid-soluble form of vitamin B1, can prevent diabetic retinopathy and all three forms of metabolic damage by stimulating transketolase activity and thus diverting excess metabolites toward the pentose pathway. Although vitamin B1 is available over the counter, the researchers at this time do not advocate self-treatment without further clinical data.     

The effect of aging on skeletal-muscle recovery from exercise: possible implications for aging athletes

Recovery from exercise is integral to the physical training process. There is a perception among older athletes that aging negatively affects the recovery process. Plausible arguments for an impaired recovery with aging are a greater susceptibility of older muscle to exercise-induced skeletal-muscle damage and a slower repair and adaptation response. Differences in the physical activity level of the research participants are rarely considered, however. This makes it difficult to differentiate the respective roles of declining physical activity and aging on the recovery process. Furthermore, the type of exercise used to induce damage and monitor recovery is often not indicative of a normal training stimulus for athletes. This review discusses the effects of aging on skeletal-muscle damage and recovery processes and highlights the limitations of many of these studies with respect to older athletes. Future research should use an exercise intervention representative of a normal training stimulus and take the physical activity level of the participants into account.     

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.     

Is DNA cut out for a long life?

Much attention has been focused on the DNA repair hypothesis of aging. Studies in mammals that seek to test the validity of this model are complicated by both the functional redundancy and the essential nature of genes involved in the repair process. Compared to mammals, the study of DNA repair and aging in yeast has considerably fewer complicating factors. In this Perspective, I discuss results presented in this month's issue of Aging Cell that address whether the types of DNA damage repaired by the base excision repair pathway cause aging in yeast.     

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.     

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.     

Tire aging: a human factors analysis of failure to warn and inform

A scenario of an automotive accident caused by tire failure is given followed by a human factors analysis of the information available to consumers on tire aging. Consumers have not been told that the age of the tire is a safety concern. It is not easy to decode the date of manufacture on tires. More publicity and prominent warnings are needed to communicate the dangers of older tires. Also, better ways to present the date of manufacture so that consumers can more easily and accurately assess tire age are needed.     

Effects of aging on Type II muscle fibers: a systematic review of the literature

The authors conducted a systematic review of the literature for scientific articles in selected databases to determine the effects of aging on Type II muscle fibers in human skeletal muscles. They found that aging of Type II muscle fibers is primarily associated with a loss of fibers and a decrease in fiber size. Morphological changes with increasing age particularly included Type II fiber grouping. There is conflicting evidence regarding the change of proportion of Type II fibers. Type II muscle fibers seem to play an important role in the aging process of human skeletal muscles. According to this literature review, loss of fibers, decrease in size, and fiber-type grouping represent major quantitative changes. Because the process of aging involves various complex phenomena such as fiber-type coexpression, however, it seems difficult to assign those changes solely to a specific fiber type.     

Lipofuscin and aging: a matter of toxic waste

Lipofuscin is membrane-bound cellular waste that can be neither degraded nor ejected from the cell but can only be diluted through cell division and subsequent growth. The fate of postmitotic cells is to accumulate lipofuscin, which as an "aging pigment" has been considered a reliable biomarker for the age of cells such as neurons and, by extension, their hosts. In the aging human brain, deposits of lipofuscin are not uniformly distributed but are concentrated in specific regions of functional interest. The prevailing thought is that the major source of lipofuscin is incomplete lysosomal degradation of damaged mitochondria. Accumulating evidence suggests that lipofuscin is not benign but can impair the functioning of seemingly unrelated cellular systems, including the ubiquitin/proteasome pathway. A damaging feedback loop of lysosomal and proteasomal inhibition may occur as lipofuscin accumulates, leading to what has been appropriately named a "garbage catastrophe." Reversing this catastrophe presents a formidable challenge.     

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.     

Winning a Battle but Losing the War? Third Sector and Social Policy in Latin America: The Case of Uruguay

This paper analyzes some aspects of the third sector’s involvement process in the provision of public social services. Using evidence garnered in previous research based on in-depth interviews, I offer elements toward an assessment of the consequences this process has produced not only in terms of the gains and losses it has produced for social policy, but also for the very identity and constitutive characteristics of the third sector. The evidence hereby compiled strengthens skepticism toward the hypothesis that sees a transformative potential in the role of the third sector in social policy in Latin America. This skepticism arises from issues detected by involved actors themselves and that are linked to the weakness of the sector as a whole.     

Practical consequences of the validation of a mathematical model in assessment of partial androgen deficiency in the aging male using bioavailable testosterone

Partial androgen deficiency or the andropause in the aging male is a complex clinical and biochemical entity that needs to be analyzed at two levels of the constituent structure: the 'deep structure' should come to light with more intensive research, while the 'surface structure' holds the attention of investigators who focus on hormone measurements in the blood to help diagnose the andropause. In this study, it is recognized that bioavailable testosterone decreases progressively during the aging process. This physiological decline may be so important, or so close to castration levels, that aged men may experience numerous symptoms of hypogonadism. The assay for bioavailable testosterone was indirectly validated with a set of equations derived from our knowledge of the law of mass action at equilibrium, as proposed by Vermeulen and colleagues in 1999. With this mathematical model, we have shown that calculated free testosterone was highly correlated with bioavailable testosterone. It is therefore concluded that the evaluation of aged men's androgenicity should rely on at least one of these free testosterone assessments (bioavailable or calculated free testosterone) for the sake of reproducibility in the construction of the 'surface structure' of the andropause in the coming years.     

Assisted Living for Lower-Income and Frail Older Persons from the Housing and Built Environment Perspective

Abstract

This paper examines the linkages between housing and supportive services from the built environmental perspective. When it comes to linking supportive services, it is usually true that the wealthier an individual is the more private resources he or she has available to define a personal support system at every step in the aging process; the poorer the individual is, the fewer choices she or he has and the successful linkages of government subsidized housing, health and supportive services become more important to successful aging of that person. Low-income and aging individuals are the real testing ground for whether current policy allows holistic support linkages to occur and whether programs are available in both the quantity and quality to empower low-income older persons with options and support choices.

The discussion that follows is limited to supportive services and aging in place in conventional housing and affordable purpose built assisted living programs and facilities; it omits institutional living. For low-income older persons, institutional care provides few if any housing choices or individual power to control support delivery, and thus linkages between cooperating support professionals and programs becomes increasingly moot.     

Nitric oxide and oxidative stress in cardiovascular aging

The long-standing free radical theory of aging, which attributes cellular pathology to the relentless accumulation of reactive oxygen species (ROS), remains attractive but controversial. Emerging insights into the molecular interactions between ROS and reactive nitrogen species (RNS) such as nitric oxide suggest that, in biological systems, one effect of increased ROS is the disruption of protein S-nitrosylation, a ubiquitous posttranslational modification system. In this way, ROS may not only damage cells but also disrupt widespread signaling pathways. Here, we discuss this phenomenon in the context of the cardiovascular system and propose that ideas regarding oxidative stress and aging need to be reevaluated to take account of the balance between oxidative and nitrosative stress.     

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.     

Effects of motor practice on cognitive disorders in older adults

The demographics of our societies have changed drastically during the past few decades. The general population is aging rapidly as human life spans continue to expand and more adults are set to mature during the next quarter century. This aging process has numerous implications for the way we live and will have particularly important impacts on health and healthcare. In particular, substantial evidence suggests that cognitive–motor function deteriorates considerably as the result of inactive life style, biological aging, and cognitive impairments. The number of individuals with Alzheimer's disease (AD), an aging-related cognitive disorder, is expected to increase significantly during the next 40 years. The development of mild cognitive impairment (MCI) or AD can exaggerate the functional declines observed in cognitive or motor performance. The functional declines affect an array of social, cognitive, mental, physical, and motor activities in our daily lives. However, recent studies suggest that cognitive, physical, motor practice, or skill learning can improve motor speed, smoothness, and accuracy in both MCI and AD patients and their age-matched healthy peers. From theoretical and practical perspectives, this paper addresses several critical aspects of motor deficits and the kinematical characteristics of motor skill development in MCI and AD populations. Empirical data will be presented relative to the sensory–motor functions of MCI and AD, the motor skill acquisition, exercise rehabilitation in older adults with memory loss, as well as the implications for therapies. Finally, this review concludes with thoughts and suggestions for future research in these areas.     

Aging with HIV: Historical and Intra-Community Differences in Experience of Aging with HIV

Gay men living with HIV/AIDS face a complex of health issues, including those associated with the aging process, long-term HIV infection (25 years or more), and side effects from Highly Active Anti-Retroviral Therapy (HAART). If aging can increase marginalization, this is more likely for the aging HIV positive gay man, who is already marginalized for being queer and living with a stigmatizing disease. This article presents findings from a study of a long-running HIV support group. It locates the members, all gay men living with HIV, in a specific historical and political context to explore how feelings of loss and the struggle to sustain community affect long-term survivors and other older HIV+ gay men. We identify specific challenges presented by aging for men who contracted HIV early in the epidemic, contrasting them with those faced by men infected with the virus later in life. While both groups appear to struggle with a vision of what life could have been, had AIDS not forced loss and change, they also celebrate the community their shared plight has enabled.     

Alterations in IGF-I affect elderly: role of physical activity

The growth hormone–insulin-like growth factor I (IGF-I) axis is an important physiological regulator muscle for development. Although there is evidence that aging muscle retains the ability to synthesize IGF-I, there is also evidence that aging may be associated with attenuation of the ability of exercise to induce an isoform of IGF-I that promotes satellite cell proliferation. However, it is clear that overexpression of IGF-I in the muscle can protect against age-related sarcopenia. Strength training appears to be the intervention of choice for the prevention and treatment of sarcopenia. IGF-I has been implicated in the loss of the muscle with age, and IGF-I expression levels change as a consequence of strength training in older adults. However, it seems that advancing age, rather than declining serum levels of IGF-I, appears to be a major determinant of life-time changes in body composition in women and men. We concluded that resistive exercise is a significant determinant of muscle mass and function. Elevated levels of IGF-I have been found in physically active compared to sedentary individuals. Recent work suggests that IGF-I as a mediator plays an important role in muscle hypertrophy and angiogenesis, both of which characterize the anabolic adaptation of muscles to exercise.     

“I'm still raring to go”: Successful aging among lesbian,gay, bisexual,and transgender older adults

While we know that minority status differentiates the experience of aging, little research has been done to examine the ways in which patterns of successful aging may differ in diverse subgroups of older adults. In this exploratory study, we investigated and described experiences of successful aging in a sample of lesbian, gay, bisexual and transgender (LGBT) older adults. Directed by a community-based participatory research process, we conducted semi-structured in-depth interviews with 22 LGBT adults, age 60 and older. We took an inductive, grounded theory approach to analyze the taped and transcribed interviews. We coded respondent experiences in four domains: physical health, mental health, emotional state and social engagement. Four gradations of successful aging emerged. Very few in our sample met the bar for “traditional success” characterized by the absence of problems in all four domains of health. Most of the sample was coping to a degree with problems and was categorized in one of two gradations on a continuum of successful aging: “surviving and thriving” and “working at it.” A small number was “ailing”: not coping well with problems. Some of the experiences that respondents described were related to LGBT status; others were related to more general processes of aging. The research suggests that a successful aging framework that is modified to include coping can better describe the experiences of LGBT older adults. The modified conceptual model outlined here may be useful in future research on this population, as well as more broadly for diverse populations of adults, and may be adapted for use in practice to assess and improve health and well-being.