Trajectories of Frailty in the five years Prior to Death Among US Veterans Born 1927-1934

Background Electronic frailty indices (eFIs) are increasingly used to identify patients at risk for morbidity and mortality. Whether eFIs capture the spectrum of frailty change, including decline, stability, and improvement is unknown. Methods In a nationwide retrospective birth-cohort of US Veterans, a validated eFI, including 31 health deficits, was calculated annually using medical record and insurance claims data (2002-2012). K-means clustering was used to assign patients into frailty trajectories measured five years prior to death. Results There were 214,250 Veterans born between 1927-1934 (mean (SD) age at death = 79.4 (2.8) years, 99.2% male, 90.3% white) with an annual eFI in the five years before death. Nine frailty trajectories were identified. Those starting at non-frail or pre-frail had two stable trajectories (non-frail to pre-frail, n=29,786 and stable pre-frail, n=28,499) and two rapidly increasing trajectories (pre-frail to moderately frail, n=28,244 and pre-frail to severely frail, n=22,596). Those who were mildly frail at baseline included one gradually increasing trajectory (mildly to moderately frail, n=33,806) and one rapidly increasing trajectory (mildly to severely frail, n=15,253). Trajectories that started at moderately or severely frail included two gradually increasing trajectories (moderately to severely frail, n=27,662 and progressing severely frail, n=14,478) and one recovering trajectory (moderately frail to mildly frail, n=13,926). Conclusions Nine frailty trajectories, including one recovering trajectory, were identified in this cohort of older US Veterans. Future work is needed to understand whether prevention and treatment strategies can improve frailty trajectories and contribute to compression of morbidity towards the end of life.

The economic value of targeting aging

Developments in life expectancy and the growing emphasis on biological and ‘healthy’ aging raise a number of important questions for health scientists and economists alike. Is it preferable to make lives healthier by compressing morbidity, or longer by extending life? What are the gains from targeting aging itself compared to efforts to eradicate specific diseases? Here we analyze existing data to evaluate the economic value of increases in life expectancy, improvements in health and treatments that target aging. We show that a compression of morbidity that improves health is more valuable than further increases in life expectancy, and that targeting aging offers potentially larger economic gains than eradicating individual diseases. We show that a slowdown in aging that increases life expectancy by 1 year is worth US$38 trillion, and by 10 years, US$367 trillion. Ultimately, the more progress that is made in improving how we age, the greater the value of further improvements.

Bcl-xL as a Modulator of Senescence and Aging

Many features of aging result from the incapacity of cells to adapt to stress conditions. When cells are overwhelmed by stress, they can undergo senescence to avoid unrestricted growth of damaged cells. Recent findings have proven that cellular senescence is more than that. A specific grade of senescence promotes embryo development, tissue remodeling and wound healing. However, constant stresses and a weakening immune system can lead to senescence chronicity with aging. The accumulation of senescent cells is directly related to tissue dysfunction and age-related pathologies. Centenarians, the most aged individuals, should accumulate senescent cells and suffer from their deleterious effects, however, they enjoy a compression of morbidity. We have shown that they overexpress B-cell lymphoma-extra large (Bcl-xL). Bcl-xL could avoid an excessive burden of senescent cells through the regulation of intrinsic apoptosis, mitochondrial bioenergetics and oxidative stress. On the other hand, Bcl-xL maintains a fully functional immune system that ensures an efficient clearance of senescent cells. Moreover, there is a paradox, as inhibitors of Bcl-xL have been employed as senolytic agents, which have been shown to protect from aging in animal models. In this review, we aim to discuss how Bcl-xL could modulate senescence-associated harmful effects in centenarians, protecting them from the burden of accumulation of senescent cells.

Mixed evidence for the compression of morbidity hypothesis for smoking elimination—a systematic literature review

Background There is debate around the composition of life years gained from smoking elimination. The aim of this study was to conduct a systematic review of the literature to synthesize existing evidence on the effect of smoking status on health expectancy and to examine whether smoking elimination leads to compression of morbidity. Methods Five databases were systematically searched for peer-reviewed articles. Studies that presented quantitative estimates of health expectancy for smokers and non-/never-smokers were eligible for inclusion. Studies were searched, selected and reviewed by two reviewers who extracted the relevant data and assessed the risk of bias of the included articles independently. Results The search identified 2491 unique records, whereof 20 articles were eligible for inclusion (including 26 cohorts). The indicators used to measure health included disability/activity limitations (n=9), health-related quality of life (EQ-5D) (n=2), weighted disabilities (n=1), self-rated health (n=9), chronic diseases (n=6), cardiovascular diseases (n=4) and cognitive impairment (n=1). Available evidence showed consistently that non-/never-smokers experience more healthy life years throughout their lives than smokers. Findings were inconsistent on the effect of smoking on the absolute number of unhealthy life years. Findings concerning the time proportionally spent unhealthy were less heterogeneous: nearly all included articles reported that non-/never-smokers experience relatively less unhealthy life years (e.g. relative compression of morbidity). Conclusions Support for the relative compression of morbidity due to smoking elimination was evident. Further research is needed into the absolute compression of morbidity hypothesis since current evidence is mixed, and methodology of studies needs to be harmonized.

Leveraging budding yeast Saccharomyces cerevisiae for discovering aging modulation substances for functional food

Background: Discovery of bioactive substances contained in functional food and the mechanism of their aging modulation are imperative steps in developing better, potent and safer functional food for promoting health and compression of morbidity in the aging population. Budding yeast (Saccharomyces cerevisiae) is invaluable model organism for aging modulation and bioactive compounds discovery. In this paper we have conceptualised a framework for achieving such aim. This framework consists of four components: discovering targets for aging modulation, discovering and validating caloric restriction mimetics, acting as cellular systems for screening natural products or compounds for aging modulation and being a biological factory for producing bioactive compounds according to the roles the yeast systems play. It have been argued that the component of being a biological factory for producing bioactive compounds has much underexplored which also present an opportunity for new active substance discovery and validation for health promotion in functional food industry.Keywords: Aging modulation, budding yeast, functional food, bioactive substances, cell factory