Physiological Decline Research Articles

Association between postural tremor and risk of disability in community-dwelling older people.

The prevalence of postural tremor increases with age and the tremor has been found to be associated with aging-related physiological decline. However, whether postural tremor in older adults is associated with adverse outcomes such as disability is unclear. This study investigated the association between postural tremor and the risk of disability in activities of daily living (ADL) among community-dwelling older people. Data were derived from a population-based study of Chinese adults aged ≥55 years. Postural tremor was assessed at baseline using a two-step method (i.e., tremor screening followed by examination of positive cases). ADL disability was determined using an 8-item questionnaire, which covered the mobility and self-care domains of ADL. Participants free of ADL disability at baseline were followed for up to 4 years. The prospective analyses included 5868 participants. Participants with postural tremor were at greater risk of incident ADL disability, particularly disability in the mobility domain of ADL. After multivariate adjustment, postural tremor was not significantly associated with incident ADL disability (multivariate-adjusted relative risk [RR]=1.05, 95% confidence interval [CI]=0.77-1.43), and was marginally associated with incident disability in the mobility domain of ADL (multivariate-adjusted RR=1.36, 95% CI=0.98-1.88). The risk of mobility-related ADL disability was significantly increased among men, but not women, with postural tremor (multivariate-adjusted RR=1.84, 95% CI=1.11-3.05). Older age and an increased number of chronic comorbidities mainly explained the higher risk of ADL disability in older people with postural tremor. Postural tremor in older adults is associated with greater incidence of ADL disability, particularly mobility-related ADL disability. The association is largely due to older age and a higher prevalence of chronic comorbidities in older people with postural tremor. Postural tremor is not a strong independent predictor of ADL disability in older people.

Relationships between dance, health and aesthetic performance in a company of mature dancers: An exploratory study

Dance with the older body is often viewed as a means to slow the physiological and cognitive decline associated with ageing or chronic health conditions. However, little research has investigated the aesthetic qualities and performance potential of mature dancers and how this might influence health outcomes. During a choreographic project bringing together a renowned contemporary dance company with one of mature dancers, a co-designed, mixed-methods approach was taken to explore the impact of a somatically informed approach to choreography on the dancers’ movement quality, efficiency and performance aesthetics. Quality-of-life measurements showed no significant differences between pre- and post-choreographic project, although high scores suggested good overall health amongst participants. Subjective changes in movement quality were observed alongside improvements in balance ability ascribed to the inward focus of the somatically informed creative process. Participants commented that they were able to achieve more, physically and aesthetically, than they had previously believed possible.

IMPACTO DO CONDICIONAMENTO FÍSICO DO CORE SOBRE O DESEMPENHO DO EQUILÍBRIO NOS IDOSOS

ABSTRACT Introduction Relevant monitoring data show that falls have become the leading cause of death in adults over 65 years old, especially among elderly people who have no exercise habits. Physiological function decline caused by the aging process can be slowed with specific training. It is believed that exercises focusing on the core muscles can benefit balance ability among the elderly. Objective The paper explores how core muscle training impacts balance performance in the elderly. Methods The article randomly divides elderly volunteers (n=24) into two groups. The experimental group received specific core physical conditioning, and the control group received no intervention. The physical quality indicators of both groups were compared and statistically analyzed after the experiment. Results The physical fitness indicators (weight, aerobic endurance, static balance ability) in the groups differed (P<0.05). Conclusion Core training can improve the elderly´s functional physical ability and static balance capacity. Evidence level II; Therapeutic Studies - Investigating the results.

(-)- Gossypol Inhibition of Musashi-Mediated Forgetting Improves Memory and Age-Dependent Memory Decline in Caenorhabditis elegans

Musashi RNA-binding proteins (MSIs) retain a pivotal role in stem cell maintenance, tumorigenesis, and nervous system development. Recently, we showed in C. elegans that Musashi (MSI-1) actively promotes forgetting upon associative learning via a 3’UTR-dependent translational expression of the Arp2/3 actin branching complex. Here, we investigated the evolutionary conserved role of MSI proteins and the effect of their pharmacological inhibition on memory. Expression of human Musashi 1 (MSI1) and Musashi 2 (MSI2) under the endogenous Musashi promoter fully rescued the phenotype of msi-1(lf) worms. Furthermore, pharmacological inhibition of human MSI1 and MSI2 activity using (-)- gossypol resulted in improved memory retention, without causing locomotor, chemotactic, or learning deficits. No drug effect was observed in msi-1(lf) treated worms. Using Western blotting and confocal microscopy, we found no changes in MSI-1 protein abundance following (-)- gossypol treatment, suggesting that Musashi gene expression remains unaltered and that the compound exerts its inhibitory effect post-translationally. Additionally, (-)- gossypol suppressed the previously seen rescue of the msi-1(lf) phenotype in worms expressing human MSI1 specifically in the AVA neuron, indicating that (-)- gossypol can regulate the Musashi pathway in a memory-related neuronal circuit in worms. Finally, treating aged worms with (-)- gossypol reversed physiological age-dependent memory decline. Taken together, our findings indicate that pharmacological inhibition of Musashi might represent a promising approach for memory modulation.

Hydroxyurea Dosing in Very Young Children (HUGKISS): Challenges of Study Design

Introduction: The acute and chronic complications of sickle cell anemia (SCA) are well-known, with many of them arising in the first few years of life. The BABY HUG trial showed that 20 mg/kg/day of hydroxyurea therapy is safe, blunts the decline of fetal hemoglobin (HbF), and is clinically beneficial for very young infants and children with SCA. Nevertheless, children treated with hydroxyurea continued to develop acute complications and acquire end organ damage. Although the BABY HUG trial established the safety and efficacy of fixed dose hydroxyurea in very young children with SCA, further study was needed to define the optimal dosing regimen to maximize benefit in this group. We describe our approach to designing and implementing the Hydroxyurea Management in Kids: Intensive versus Stable Dosage Strategies (HUGKISS) study, which assessed the feasibility of enrolling and randomizing very young children with SCA to intensified versus fixed doses of hydroxyurea. The hematologic and clinical effects of both doses were also monitored. Methods: The HUGKISS trial was designed as a single-blind, multicenter, randomized controlled pilot study. It was felt that the objectives of HUGKISS could be safely and more efficiently obtained with a single-blind design (with investigators blinded), because a double-blind design would be logistically challenging and would place significant burden on families and pharmacies. For example, in one double-blind design, caregivers would have to administer two aliquots of study drug (hydroxyurea + hydroxyurea or hydroxyurea + placebo), thereby providing a potential source for medication error. However, because the HUGKISS study required dosage adjustment of hydroxyurea based on complete blood count results, a HUGKISS Enabled Local Provider for Evaluating Response (HELPER) was utilized. Each HELPER was an unblinded local medical provider, unaffiliated with the steering committee or data analysis, who was knowledgeable about SCA. This individual monitored hydroxyurea concordance and toxicities in real time. All patients received hydroxyurea at 20 mg/kg/day for 8 weeks. If they were stable and adherent, they were randomized to either continued fixed dosing or intensified dosing, which involved escalation of hydroxyurea dosing every 8 weeks to a maximum of 35 mg/kg/day. While the primary endpoint was assessing feasibility of enrollment and randomization, the main secondary endpoint assessed was changes in HbF levels. This choice reflected the age of the patient population, which would be undergoing a physiologic decline in HbF during the study period. We monitored adherence via the Medication Adherence Measure (MAM) and measurement of remaining hydroxyurea suspension in the prescribed bottle. Both were performed every four weeks. A medication possession ratio was calculated using the results from both methods, and used to quantitate adherence. Enrollment screening logs were also maintained at all sites. The most common reason for declining participation in HUGKISS was that families desired more time to "think about" hydroxyurea and participation in a trial, followed by disinterest in using hydroxyurea, and a fear of participating in clinical trials. Conclusion: Important considerations when designing trials involving young children with SCA include choice of endpoints, obtaining adequate enrollment, maintaining blinding of a liquid formulation with dose adjustments, and assessment of medication adherence. The HUGKISS study employed a novel single-blind design to facilitate safe and efficient administration of hydroxyurea for families, while also ensuring close monitoring of toxicities through a HELPER.

Triterpenoids and Polysaccharides from Ganoderma lucidum Improve the Histomorphology and Function of Testes in Middle-Aged Male Mice by Alleviating Oxidative Stress and Cellular Apoptosis.

Aging is an inevitable physiological process accompanied by a decline in body physiology, including male fertility. A preparation from Ganoderma lucidum (GL) containing triterpenes and polysaccharides has been shown to have anti-aging properties. In the current study, the effects of GL on mating ability, testosterone secretion, and testicular structure and function were observed in middle-aged male mice. The GL preparation was administered orally to mice for 2 to 5 months, and then behavioral, serological, and histopathological examinations were performed. Results showed that in the GL group of mice, the mating latency was shortened, the number of pursuits within 20 min was increased, and the mating success rate was higher compared to control mice. Additionally, the levels of serum testosterone, cell proliferation (Ki67), and sperm-specific lactate dehydrogenase (LDH)-C4 were increased, while the levels of senescence-related protein p16 and cellular apoptosis were decreased in GL mice. Testicular spermatogenic cells and sperm and stromal cells were reduced and exhibited structural disorder in 11- and 14-month-old control mice, while these changes were improved compared to age-matched mice receiving the GL preparation. Furthermore, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and the pro-apoptotic protein Bax were decreased, while the anti-apoptotic protein Bcl-2 was increased in GL mice. Finally, the mitochondrial structure was relatively complete in GL mice compared to controls. Therefore, GL has the potential to improve testicular structure and function in middle-aged male mice by alleviating oxidative stress, maintaining mitochondrial homeostasis, and reducing cellular apoptosis.

P098 "It's just [complicated] sleep": Discourses of sleep and ageing in the media

Abstract Background Sleep disturbances have been reported to increase with older age. However, sleep-related beliefs and practices also appear to change with ageing and disease, having implications for measurement and management of sleep among older people. Analysis of sleep-related messaging within mainstream media contributes to understanding social discourses of sleep and ageing. Method Texts from New Zealand’s main free online news source “Stuff” were collated using key words “sleep” together with ''ageing'', ''older'', ''elderly'', or ''dementia'' between December 2018 and December 2021. A total of 38 relevant articles were collated. A critical discourse analysis was used to describe the texts then interpret them in relation to discursive practices and wider social explanations. Findings Texts were categorised under basic contextual themes: general ageing, disease, beauty, and treatments. Discursive constructions described an inevitable decline of sleep with ageing, including the tensions between a likely physiological decline alongside individual failures to achieve good sleep; sleep’s role as both a remedy and risk for diseases (such as dementia); and the simplification of solutions for self-managing sleep alongside recognition of the complexity of sleep. Conclusions Social discourses of sleep and ageing within the mainstream New Zealand media were subtle and contradictory. Punctured with tensions between endorsing sleep practices and purchases to prevent age-related decline whilst also asserting that decline is inevitable due to the complexity of the ageing body and modern society. Findings will inform future research in the field of sleep as a concept and practice among older people.

Frailty and muscle weakness in elderly patients with asthma and their association with cumulative lifetime oral corticosteroid exposure

BackgroundFrailty is a geriatric syndrome of age-related physiological decline, which is associated with higher mortality and decreased healthy life expectancy, and muscle weakness is one of the presentations of frailty. We investigated an association between lifetime oral corticosteroid (OCS) exposure with frailty and muscle weakness among elderly patients with asthma. MethodsWe studied 203 consecutive elderly outpatients with asthma aged ≥60 years old. They were classified into three groups according to their cumulative lifetime OCS dose (lifetime non-users, lower-dose users, and higher-dose users), which was retrospectively estimated from the response to a structured questionnaire. The prevalence of frailty determined by the Kihon Checklist was compared between the three groups. Hand-grip strength, and lean mass index were also measured as markers of muscle strength. ResultsThirty-seven percent of the patients studied were considered frail. Higher cumulative lifetime OCS exposure was associated with a significantly higher prevalence of frailty (33% in lifetime non-users, 59% in lower-dose users, and 68% in higher-dose users; P for trend <0.005). This was also associated with lower hand-grip strength in both sexes (P for trend; 0.012 in men, and 0.020 in women), and lower lean mass index in men (P for trend 0.002). However, current doses of OCS were not significantly associated with these outcomes. ConclusionsCumulative lifetime OCS exposure was associated with a higher prevalence of frailty and muscle weakness. These findings emphasize the importance of minimizing lifetime OCS exposure for the prolongation of healthy life expectancy in patients with asthma.

Role of apoptosis and autophagy in ovarian follicle pool decline in children and women diagnosed with benign or malignant extra-ovarian conditions.

Which biological mechanisms are responsible for physiological ovarian reserve decline owing to aging, or pathological follicle depletion triggered by inflammation or a pro-oxidant environment throughout a woman's lifetime? Ovarian follicle pool size is modulated by both apoptosis and autophagy, the first responsible for its physiological decline over time and increasing in the event of prior chemotherapy in children, and the latter playing a major role in physiological ovarian follicle pool diminution before puberty. Among the different pathways of controlled cell death, apoptosis and autophagy are implicated in follicle loss. Apoptosis participates in eliminating damaged follicles, such as those impaired by chemotherapy (CHT), but its involvement in physiological age-related follicle decline is less well understood. Autophagy has proved crucial in follicle quiescence maintenance in murine models, but its contribution to human follicle pool modulation is still unclear. This retrospective study included 84 patients with benign or malignant extra-ovarian conditions aged between 1 and 35 years, with ovarian tissue stored for histological analyses at the time of cryopreservation (between 2012 and 2021) at a tertiary care center. Ovarian fragments were used for the following analyses: hematoxylin and eosin staining for follicle count and classification; cleaved caspase-3 immunostaining to identify follicle apoptosis; and microtubule-associated proteins 1A/1B light chain 3B immunolabeling to detect follicle autophagy. Transmission electron microscopy was also carried out to investigate ultrastructural features of oocytes and granulosa cells. All analyses stratified patients by age, menarchal status (premenarchal = 32; postmenarchal = 52), potentially gonadotoxic CHT before cryopreservation (n = 14), presence of endometriosis and use of hormonal treatment. Premenarchal patients had a larger follicle pool in terms of total follicle density [mean, range 4979.98 (342.2-21789) versus 918.8 (26.18-3983), P < 0.001], but higher rates of morphologically abnormal [8.52 (0-25.37)% versus 3.54 (0-17.5)%, P < 0.001] and atretic [15.8 (0‒31.85)% versus 10.6 (0-33.33)%, P < 0.01] follicles than postmenarchal subjects. Apoptosis rates did not change with increasing age [27.94 (0-93.2)% in prepubertal subjects and 29.5 (0-100)% in postpubertal subjects], but autophagic follicles were around 10 times more common in premenarchal than postmenarchal subjects [10.21 (0-62.3)% versus 1.34 (0-25)%, P < 0.001], playing a crucial role in age-related follicle decline and elimination of 'abnormal' follicles, that are rarely seen after menarche. The impact of diagnosis and previous CHT varied according to age. In premenarchal patients with previous CHT, significantly more apoptotic [40.22 (0-100)% versus 26.79 (0-87)%, P < 0.05] and fewer abnormal [3.84 (0-10-76)% versus 9.83 (0-25.37)%, P < 0.01] follicles were detected than in subjects with no CHT prior to ovarian tissue cryopreservation, suggesting a direct effect on follicle elimination, especially of those with abnormalities. In postmenarchal subjects with previous CHT, quiescent follicle rates were lower than in patients with no CHT before tissue freezing [71.57 (0-100)% versus 85.89 (50-100)%, P < 0.05], suggesting accelerated follicle activation and growth. Moreover, increased autophagic activity was observed in the event of a cancer diagnosis compared to benign conditions after puberty [26.27 (0-100)% versus 9.48 (0-29.41)%, respectively, P < 0.05]. The impact of specific CHT protocols could not be investigated since the group of patients with previous CHT was highly heterogeneous. This study yields a deeper understanding of regulation of the follicle pool decline, showing for the first time that both apoptosis and autophagy pathways are involved in physiological follicle depletion, the latter being crucial before puberty. Moreover, our data showed a different response to non-physiological damage according to age, with higher apoptosis rates only in premenarchal subjects with previous CHT, confirming that this pathway is activated by drugs known to induce DNA damage in oocytes, such as alkylating agents, but not by cancer itself. This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (F.R.S.-FNRS/FRIA FC29657 awarded to L.C., CDR J.0063.20 and grant 5/4/150/5 awarded to M.M.D.), grants from the Fondation contre le Cancer (grant 2018-042 awarded to A.Ca.), the Fondazione Comunitaria del Varesotto and Provincia di Varese ('Amalia Griffini' Fellowship in Gynecology and Obstetrics awarded to A.Ce.), Fonds Spéciaux de Recherche, Fondation St Luc and donations from the Ferrero family. The authors have no competing interests to declare. N/A.

In utero exposure to the Great Depression is reflected in late-life epigenetic aging signatures

Research on maternal-fetal epigenetic programming argues that adverse exposures to the intrauterine environment can have long-term effects on adult morbidity and mortality. However, causal research on epigenetic programming in humans at a population level is rare and is often unable to separate intrauterine effects from conditions in the postnatal period that may continue to impact child development. In this study, we used a quasi-natural experiment that leverages state-year variation in economic shocks during the Great Depression to examine the causal effect of environmental exposures in early life on late-life accelerated epigenetic aging for 832 participants in the US Health and Retirement Study (HRS). HRS is the first population-representative study to collect epigenome-wide DNA methylation data that has the sample size and geographic variation necessary to exploit quasi-random variation in state environments, which expands possibilities for causal research in epigenetics. Our findings suggest that exposure to changing economic conditions in the 1930s had lasting impacts on next-generation epigenetic aging signatures that were developed to predict mortality risk (GrimAge) and physiological decline (DunedinPoAm). We show that these effects are localized to the in utero period specifically as opposed to the preconception, postnatal, childhood, or early adolescent periods. After evaluating endogenous shifts in mortality and fertility related to Depression-era birth cohorts, we conclude that these effects likely represent lower bound estimates of the true impacts of the economic shock on long-term epigenetic aging.

177 GENOME-WIDE ASSOCIATION ANALYSIS OF THE FRAILTY PHENOTYPE IN UK BIOBANK HIGHLIGHTS CARDIOMETABOLIC AND AUTOIMMUNE SIGNATURES IN AGEING

Abstract Background Frailty is a state of advanced biological age that is characterized by multisystem physiological decline and advanced risk to adverse health outcomes. One approach to defining frailty is using the Fried frailty phenotype, a five-point list of health-related criteria used to score individuals as non-frail, pre-frail, or frail. The biological basis of frailty is not fully understood, nor why some experience frailty at younger ages. Between 30%-45% of frailty risk is estimated to be genetic. This study aimed to investigate the genetic basis of frailty phenotype risk using data from UK Biobank. Methods UK Biobank is a large-scale biomedical database of community dwelling adults (n = 502,529, age range: 37-73 years, 54% female). UK Biobank has genome-wide genotyping (approx. 93 million variants), health, and demographic data for all participants. A genome-wide association study (GWAS) of the frailty phenotype was performed on British and Irish adults aged 60 to 70 years (n = 157,720) to identify heritable factors which predict frailty progression in later life. Functional mapping was performed to determine genes and biological pathways enriched in GWAS results. Results 95 single nucleotide polymorphisms (SNPs) from three independent genomic risk loci were significantly associated (p &amp;lt; 5e-8) with the frailty phenotype in UK Biobank participants. Three genes, PPP1R3A, LONRF2, and AIF1 were statistically enriched with genetic variants. Tissue-specific expression analysis indicated genes differentially expressed in blood vessels were enriched. Linkage Disequilibrium Score Regression (lambda = 1.2005, intercept = 1.0006) indicated GWAS test statistic inflation resulting from polygenicity. SNP-based heritability was estimated to be 6.34% (SE: 0.36%). Conclusion SNP-based heritability of the frailty phenotype was lower than expected in comparison to previous reports of 30%-45%. Statistically significant genomic risk loci, genes, and tissue-enrichment pointed towards dysregulation of cardiometabolic, cardiovascular, and immunological processes in frailty risk, contrasting to brain pathways enriched in previous genomic analyses of the frailty index.

The high pH value of alkaline salt destroys the root membrane permeability of Reaumuria trigyna and leads to its serious physiological decline.

Variable climatic conditions frequently have harmful effects on plants. Reaumuria trigyna, a salt-secreting xerophytic shrub, occurs in Inner Mongolia, which has a poor environment for plant growth. To explore the physiological and molecular mechanisms of R. trigyna in response to environmental stress, this study investigated the abiotic resistance of R. trigyna in terms of growth regulation, antioxidant defense, osmotic regulation, ion transport, and ion homeostasis-related genes. R. trigyna seedlings were treated with 400 mM NaCl, 400 mM neutral salts (NaCl:Na2SO4 = 9:1), 50 mM alkaline salts (NaHCO3:Na2CO3 = 9:1), 10% polyethylene glycol (PEG), and UV-B. Seedlings under 400 mM NaCl and 400 mM neutral salt stress showed less damage. While alkaline salt, PEG, and UV stress caused more damage, specifically in oxidative damage, proline levels, electrolyte leakage, and activation of antioxidant defenses. Furthermore, under the abiotic stress treatments, the accumulation of Na+ increased while the accumulation of K+ decreased. Further analysis showed that the flow rate of Na+ and K+ under alkaline salt stress was higher than under neutral salt stress. Neutral salt induced high expression of RtNHX1 and RtSOS1, while alkaline salt induced high expression of RtHKT1, and alkaline salt stress significantly reduced the activity of root cells. These results indicated that R. trigyna seedlings were more tolerant to neutral than alkaline salts; this might be because root activity decreased at high pH levels, which impaired membrane permeability and the ion transfer system, leading to an imbalance between Na+ and K+, and in turn to excessive accumulation of reactive oxygen species (ROS) and decreased plant stress resistance.

The energetic cost of allostasis and allostatic load

Chronic psychosocial stress increases disease risk and mortality, but the underlying mechanisms remain largely unclear. Here we outline an energy-based model for the transduction of chronic stress into disease over time. The energetic model of allostatic load (EMAL) emphasizes the energetic cost of allostasis and allostatic load, where the “load” is the additional energetic burden required to support allostasis and stress-induced energy needs. Living organisms have a limited capacity to consume energy. Overconsumption of energy by allostatic brain-body processes leads to hypermetabolism, defined as excess energy expenditure above the organism’s optimum. In turn, hypermetabolism accelerates physiological decline in cells, laboratory animals, and humans, and may drive biological aging. Therefore, we propose that the transition from adaptive allostasis to maladaptive allostatic states, allostatic load, and allostatic overload arises when the added energetic cost of stress competes with longevity-promoting growth, maintenance, and repair. Mechanistically, the energetic restriction of growth, maintenance and repair processes leads to the progressive wear-and-tear of molecular and organ systems. The proposed model makes testable predictions around the physiological, cellular, and sub-cellular energetic mechanisms that transduce chronic stress into disease risk and mortality. We also highlight new avenues to quantify allostatic load and its link to health across the lifespan, via the integration of systemic and cellular energy expenditure measurements together with classic allostatic load biomarkers.

Plasma membrane and brain dysfunction of the old: Do we age from our membranes?

One of the characteristics of aging is a gradual hypo-responsiveness of cells to extrinsic stimuli, mainly evident in the pathways that are under hormone control, both in the brain and in peripheral tissues. Age-related resistance, i.e., reduced response of receptors to their ligands, has been shown to Insulin and also to leptin, thyroid hormones and glucocorticoids. In addition, lower activity has been reported in aging for ß-adrenergic receptors, adenosine A2B receptor, and several other G-protein-coupled receptors. One of the mechanisms proposed to explain the loss of sensitivity to hormones and neurotransmitters with age is the loss of receptors, which has been observed in several tissues. Another mechanism that is finding more and more experimental support is related to the changes that occur with age in the lipid composition of the neuronal plasma membrane, which are responsible for changes in the receptors’ coupling efficiency to ligands, signal attenuation and pathway desensitization. In fact, recent works have shown that altered membrane composition—as occurs during neuronal aging—underlies reduced response to glutamate, to the neurotrophin BDNF, and to insulin, all these leading to cognition decay and epigenetic alterations in the old. In this review we present evidence that altered functions of membrane receptors due to altered plasma membrane properties may be a triggering factor in physiological decline, decreased brain function, and increased vulnerability to neuropathology in aging.

Aging and hypertension in kidney function decline: A 10 year population-based study.

BackgroundAging is associated with a physiological decline in kidney function (KFD). In this study, we aimed to describe the impact of age on the rate of KFD and its interplay with risk factors for chronic kidney disease (CKD), considering mainly hypertension (HT), in the general population.Materials and methodsParticipants of European descent, aged 35–75, were recruited from a populational cohort in Lausanne, Switzerland. Participants with a 10 year follow-up were selected. KFD was defined as the difference in estimated glomerular filtration rate (eGFR) between baseline and follow-up, divided by the observation period. Multivariate linear regressions were used with KFD as the outcome and age as the main predictor. HT was tested as a modifying factor.ResultsWe included 4,163 participants with mean age 52.2 ± 10.4, 44.7% men, 31.9% HT, and 5.0% diabetics. Mean baseline eGFR was 85.9 ± 14.6 ml/min/1.73 m2. Mean KFD was –0.49 ± 1.08 ml/min/1.73 m2 per year with 70% of participants decreasing their eGFR during follow-up. The relationship between age and KFD was non-linear and age was divided in tertiles. Old participants had faster rates of KFD as compared to young and middle-age participants (p < 0.001). A significant interaction was found between age and HT on KFD prediction (p < 0.001). In HT participants, KFD was significantly different across tertiles of age (p < 0.001). On contrary, KFD was not different across tertiles of age in non-HT participants.ConclusionA physiological KFD is present over time in the general population. Age contributes non-linearly to the rate of this decline with older subjects declining the fastest. The presence of HT is a major contributing factor in this setting as KFD worsened with age only in hypertensive participants. Thus, HT represents an important pathological factor aggravating the age-related physiological decline in eGFR in the general population.

CT-511 Clinical Characteristics and Response Outcomes in Older Multiple Myeloma Patients Who Received Idecabtagene Vicleucel: A Single Center Study

Multiple myeloma (MM) is a disease of older adults with a median age of 69y at the time of diagnosis. Older patients remain at higher risk for poor outcomes due to physical and physiological decline with aging. To study clinical characteristics and outcomes in older MM patients who received CAR-T therapy. Charts were reviewed retrospectively for older (≥65y) MM patients who received ide-cel between 8/30/2021-05/31/2022. Descriptive statistics were used to analyze clinical characteristics such as age, polypharmacy, comorbidities, history of fall, peripheral neuropathy (active or history), and organ dysfunction (active or history; cardiac, pulmonary, neuro, and/or renal) at infusion. Response outcomes were evaluated using IMWG criteria with the best overall response rate (ORR) recorded and compared to KarMMa study results for older patients (≥65y, n=45) (Munshi et al., NEJM 2021; 384:705-716). In 16 patients (median: 70y, range: 65-83y) (75% ineligible for KarMMa trial), the prevalence of polypharmacy (5+ drugs), excessive polypharmacy (10+ drugs), 4+ comorbidities, history of falls, neuropathy, and organ dysfunction was 94%, 56%, 81%, 37%, 62%, and 50% respectively. Ten patients with ≥30 days of follow up were analyzed for response outcomes. With a median follow up duration of 3.2 months, best ORR was 70% (3 sCR, 1 CR, 2 VGPR, 1 PR, 3 SD/MR), which was comparable to KarMMa study results (ORR > 50%, 95% CI). CRS was grade 1-2 and no major adverse events observed. In a subgroup analysis of eight patients (>70y old), the prevalence of the above characteristics was 100%, 87%, 87%, 37%, 62%, and 62% respectively. For six patients with a median follow up of 4.2 months, best ORR was 100% (2 sCR, 1 CR, 2 VGPR, 1 PR), which was better than KarMMa study results (ORR > 50%, 95% CI). In this small group of older patients, the prevalence of polypharmacy, comorbidities, history of falls, and peripheral neuropathy were higher compared to published reports for general and/or oncology older population. Robust responses and no major toxicities were observed in all patients, especially septua & octogenarians, despite their physical and physiological limitations.

370 Correlation Between the Electronic Frailty Index and Hospitalization Mortality in Older Adults Infected with SARS-CoV-2

370 Correlation Between the Electronic Frailty Index and Hospitalization Mortality in Older Adults Infected with SARS-CoV-2

A Literature Review: The Effect of Giving Lavender Aromatherapy On Sleep Quality In The Elderly

Elderly is the final stage of the development of the human life cycle, aging is generally defined as a progressive physiological decline after the reproductive stage of life. Common health problems in the elderly are sleep disturbances. Sleep disorders or insomnia is a condition of a person who does not get enough sleep at night, wakes up at night, or wakes up too early. The purpose of the literature review: to study the effect of using lavender aromatherapy on sleep quality in the elderly. The method used is a traditional review with the samples being accredited national and international journals. With inclusion criteria, national and international journals from different databases were selected independently by the researcher. The results: the use of lavender aromatherapy improves sleep quality in the elderly, with p value = 0.000. Improved sleep quality occurs by giving essential oils every night for 7 consecutive days. Conclusion: the use of lavender aromatherapy can be used to improve sleep quality in the elderly. Suggestion: for the elderly who have sleep disorders, you can use 5-6 drops of lavender aromatherapy oil on their pillows every night before going to bed.

The Efficacy of Fractional CO2 Laser in the Treatment of Genitourinary Syndrome of Menopause: A Large Prospective Observational Study

Background: Genitourinary syndrome of menopause (GSM) majorly caused by the physiological decline in estrogen, affects up to 90% of menopausal women. Hormonal therapy seems to be an effective treatment, often not executable for contraindication or patient’s low compliance to local or systemic medical therapy. Fractional CO2 laser therapy is an emerging and effective choice for women affected by vulvo-vaginal atrophy (VVA), promoting collagen regeneration and improving blood flow of the vaginal mucosa and elasticity of tissues. Methods: Ninety-two menopausal Patients affected by vulvo-vaginal atrophy (VVA) were considered for the present prospective observational study. All women were treated with Fractional CO2 laser Lumenis AcuPulse in a fractionated sequential mode laser pulse. Patients were requested to complete questionnaires regarding the Female Sexual Functional Index (FSFI), Female Sexual Distress Scale (FSDS) and severity of Most Bothersome Symptoms (MBS) at baseline (T0) and at three-month following three-treatment-sessions (T1). Results: Data indicated a significant improvement of MBS (vaginal itching (p &lt; 0.0001), post-coital vaginal bleeding (p &lt; 0.002), vaginal dryness (p &lt; 0.0001), dyspareunia (p &lt; 0.0001) and dysuria (p &lt; 0.0001), higher Vaginal Health Index Score (VHIS) (4.1 ± 1.21; 95% CI = 3.84–4.35) and reduces pH (–0.53 ± 0.24; 95% CI = 0.48–0.58) after CO2 laser treatment. A significantly improvement of FSFI Total score (p &lt; 0.0001) and FSDS (p &lt; 0.0001) have been demonstrated. Conclusions: Fractional CO2 laser improves vaginal health as well as signs and symptoms associated with GSM, while significantly elevating quality of life and sexual functionality among postmenopausal symptomatic women.

Acceleration-based gait analysis for frailty assessment in older adults

Frailty in older individuals has been a hot research topic in the past two decades. This syndrome of physiological decline is characterized by damage to physical function. In the literature, walking speed and gait variability have been discussed and identified as major indicators of frailty. Short walking tests under supervised conditions are frequently considered when assessing the frailty status, where the subject is instructed to walk a certain distance, and the speed and temporospatial features are compared to thresholds. In this paper, we propose a more generalized and fully automated approach using wearable sensors, by suggesting a set of parameters extracted from acceleration signals. The interconnections between these variables, which are related to the gait quality and the frailty trajectory of the subject, are investigated. This study was done on older adults of diverse profiles, in free-living conditions during their daily routine, without any predefined protocol.