For much of the 20th century the ageing process was thought to be the result of the interplay of many different biological processes, each with relatively small effects on organismal lifespan. However, this model is no longer tenable. Rather it seems a few biological mechanisms, including nutrient sensing, telomere attrition and cellular senescence, mediate large effects on health and longevity. Biogerontology may have suffered from initial delusions of complexity. However, we argue that it is premature to assume either that the list of biological processes influencing lifespan is now comprehensive or that these mechanisms act independently of each other. A case in point is provided by recent work linking together changes in RNA splicing with advancing age and the ability of polyphenolics based on resveratrol to reverse replicative senescence. In this opinion piece, we propose a novel model in which the factors regulating splice restriction and those controlling cell senescence intersect across chronological and divisional time, giving rise to senescent and growing cells with more diverse properties than previously thought. We also consider therapeutic opportunities and potential problems in the light of this revised conceptual understanding of human cell senescence and ageing.
Posted: January 8, 2020, 3:10 pm
Background: Even though poor lighting at nighttime is an important risk factor for falls (and most falls occur during the night), lighting interventions to improve nightly lighting from bed to bathroom are rarely evaluated for fall prevention. Objective: We tested the hypothesis that an automated guiding light would reduce nightly fear of falling (FOF) and increase sleep quality of community-dwelling older people. Methods: This study had a pragmatic uncontrolled before-after design, including participants during a period of 8 months if they (i) were aged at least 65 years, (ii) ambulated independently at night, and (iii) had no cognitive or audiovisual impairments obstructing outcome measurement. Automated LED strips (GightTM) were installed in the participants’ homes. The primary outcome measure was overnight FOF on a scale of 0–10. Secondary outcome measures included sleep quality on a scale of 0–10 and fall rate. Additionally, a sample of participants was interviewed about their experiences with Gight. Results: Sixty-four participants were included (mean age: 80.8 ± 8.1 years; 89% living independently). Mean study length was 118 days (range: 30–231). In the intention-to-treat analysis, overnight FOF declined from 5.5 ± 3.0 to 3.8 ± 3.2 (p = 0.001), and sleep quality increased from 6.7 ± 2.4 to 7.4 ± 1.7 (p = 0.012). The fall rate during the study was too low to detect changes. Participants appreciated Gight (8.4 ± 0.8 on a scale of 10), and the majority (57%) reported a subjective decrease in FOF. Conclusion: Gight shows promising results for overnight FOF and sleep quality, but the effect of lighting interventions on fall rate should be evaluated further before widespread implementation.
Posted: January 8, 2020, 7:12 am
Accumulation of damage is generally considered the cause of aging. Interventions that delay aging mobilize mechanisms that protect and repair cellular components. Consequently, research has been focused on studying the protective and homeostatic mechanisms within cells. However, in humans and other multicellular organisms, cells are surrounded by extracellular matrices (ECMs), which are important for tissue structure, function, and intercellular communication. During aging, components of the ECM become damaged through fragmentation, glycation, crosslinking, and accumulation of protein aggregation, all of which contribute to age-related pathologies. Interestingly, placing senescent cells into a young ECM rejuvenates them. Furthermore, we found that many longevity-assurances pathways reactivate de novo synthesis of ECM proteins during aging. This raises the question of what constitutes a young ECM to reverse aging or maintain health? In order to make inroads to answering this question, I suggest a systems-level approach of quantifying the matrisome or ECM compositions reflecting health, pathology, or phenotype and propose a novel term, the “matreotype,” to describe this. The matreotype is defined as the composition and modification of ECM or matrisome proteins associated with or caused by a phenotype, such as longevity, or a distinct and acute physiological state, as observed during aging or disease. Every cell type produces its unique ECM. Intriguingly, cancer-cell types can even be identified based on their unique ECM composition. Thus, the matreotype reflects cellular identity and physiological status. Defined matreotypes could be used as biomarkers or prognostic factors for disease or health status during aging with potential relevance for personalized medicine. Treatment with biologics that alter ECM-to-cell mechanotransduction might be a strategy to reverse age-associated pathologies. An understanding of how to reverse from an old to a young matreotype might point toward novel strategies to rejuvenate cells and help maintain tissue homeostasis to promote health during aging.
Posted: December 13, 2019, 10:02 am
The global population is aging, and as the population ages, high-risk alcohol and other drug use, particularly cannabis and prescription medications, is growing among older adults (OA). OA, defined here as 50 years of age and older, have a number of unique vulnerabilities to drug and alcohol use due to both biological as well as psychosocial factors compared to younger adults. Understanding the wide spectrum of these vulnerabilities is important to assessment, diagnosis, and intervention. Specific techniques, assessment tools, and interventions known to be effective in OA are reviewed.
Posted: December 6, 2019, 8:52 am
Posted: December 4, 2019, 8:59 am
Loss of regenerative capacity is a normal part of aging. However, some organisms, such as the Mexican axolotl, retain striking regenerative capacity throughout their lives. Moreover, the development of age-related diseases is rare in this organism. In this review, we will explore how axolotls are used as a model system to study regenerative processes, the exciting new technological advancements now available for this model, and how we can apply the lessons we learn from studying regeneration in the axolotl to understand, and potentially treat, age-related decline in humans.
Posted: November 28, 2019, 8:32 am
As populations age globally, the health of older adults is looming larger on the agendas of public health bodies. In particular, the priority is to ensure that older adults remain healthy, independent, and engaged in their communities. In other words, ensuring that increasing life spans are matched by increasing “health spans,” meaning years spent in good health. Chronic conditions such as cancer or respiratory and cardiovascular diseases account for the bulk of the disease burden in older adults, and the consensus is that these can best be tackled by effective primary prevention. However, given the diverse nature of older populations, whose prior health experiences can be complicated by multi-morbidity and poly-pharmacy, effective primary prevention can be challenging. One approach that is gaining momentum is what is called “precision” or P4 medicine. The acronym stands for “predictive, personalized, preventive, participatory” medicine, and is based on the premise that preventing disease is better than treating it. However, effective prevention requires the ability to predict disease risk for a given patient, the tailoring of treatment to their circumstances, and their consent for or participation in the offered treatment. A P4 approach may seem counter-intuitive, given that vaccination is generally considered a public health intervention. However, in this article, we discuss the application of P4 medicine as a complement to planning the vaccination of older individuals, with a special focus on the important role that vaccine-preventable infections play in the burden of non-communicable disease.
Posted: November 26, 2019, 1:56 pm
Posted: October 30, 2019, 7:26 am
Posted: October 11, 2019, 8:45 am
Background: Studies show that regular moderate to vigorous physical activity is associated with a lower risk of cardiovascular disease, certain cancers, and premature death, but few studies have examined associations of light-intensity physical activity (LPA) and mortality, especially among older adults. Objectives: The aim of this study was to investigate the association of LPA with the risks of death from all causes, cancer, cardiovascular diseases, and respiratory diseases among older adults in the Cancer Prevention Study-II Nutrition Cohort (CPS-II NC). Methods: Analyses included 123,232 participants in CPS-II NC, among whom 46,829 died during follow-up (1993–2014). Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for self-reported leisure time LPA associated with mortality. Results: Engaging in little or no LPA (#x3c;3 metabolic equivalent [MET]-h/week) was associated with a 16% higher risk of all-cause mortality (HR 1.16, 95% CI 1.12–1.20) compared to engaging in some LPA (3 to #x3c;9 MET-h/week) after adjusting for moderate to vigorous physical activity. However, there was no evidence of a dose-response relationship. A statistically significant interaction with age suggested that more LPA was associated with a lower risk of respiratory disease mortality only among participants aged ≥70 years (21+ vs. 3 to #x3c;9 MET-h/week, HR 0.78, 95% CI 0.66–0.91; pint = 0.003). Conclusions: In this prospective study of older adults, accumulating little/no leisure time LPA was associated with a higher risk of mortality. It is of substantial public health value to demonstrate the potential benefits of engaging in any activity, even if light in intensity, among older adults given the aging US population.
Posted: October 10, 2019, 8:13 am
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