Healthy Aging Research Articles

The Hidden Dangers of Sedentary Living: Insights into Molecular, Cellular, and Systemic Mechanisms

With the aging of the global population, neurodegenerative diseases are emerging as a major public health issue. The adoption of a less sedentary lifestyle has been shown to have a beneficial effect on cognitive decline, but the molecular mechanisms responsible are less clear. Here we provide a detailed analysis of the complex molecular, cellular, and systemic mechanisms underlying age-related cognitive decline and how lifestyle choices influence these processes. A review of the evidence from animal models, human studies, and postmortem analyses emphasizes the importance of integrating physical exercise with cognitive, multisensory, and motor stimulation as part of a multifaceted approach to mitigating cognitive decline. We highlight the potential of these non-pharmacological interventions to address key aging hallmarks, such as genomic instability, telomere attrition, and neuroinflammation, and underscore the need for comprehensive and personalized strategies to promote cognitive resilience and healthy aging.

7985 Insights into the Menopausal Transition: A Comparative Analysis of Hypothalamic Reproductive Aging in Women and a Mouse Model of Menopause

Abstract Disclosure: J.C. Bloom: None. S.A. Pereira: None. E. Torres Jimenez: None. D.C. Page: None. V.M. Navarro: None. Menopause onset is the major determinant of reproductive lifespan in women and is characterized by the decline in estrogen production from the ovary. While much of our current understanding of the menopause transition in humans comes from a series of observational longitudinal studies initiated in the 1980s and 1990s, the mechanisms by which reproductive aging impacts healthy brain aging remains a profoundly under-studied aspect of women’s health. The hypothalamus, a hub of homeostatic and temperature regulation, is highly sensitive to changes in sex steroid levels. Recently, activation of the neurokinin 3 receptor (NK3R) by neurokinin B (NKB) has been linked to the onset of vasomotor symptoms (VMS) during menopausal transition. NKB is secreted by hypothalamic Kisspeptin, NKB, Dynorphin (KNDy) neurons in response to decreasing estradiol levels. Here, we present a comparative study of the expression trajectories of the KNDy genes (KISS1, TAC3, PDYN, respectively) and NK3R (TACR3) in hypothalamic samples of humans across menopause and a mouse model of peri- and post-menopause (short- and long-term ovariectomy (OVX), respectively). RNA-sequencing data of human and mouse hypothalamic samples revealed a high correlation in the expression profile of the KNDy/NK3R genes between both species. Further investigation has revealed a highly conserved pool of genes in human and mouse hypothalami that correlate with TACR3 upon decline of circulating sex steroids. Thus, by examining conserved gene expression patterns across this critical reproductive period, we have been able to identify novel candidate targets involved in menopausal transition which may serve to better elucidate the biology of menopause-associated conditions affecting the brain, such as VMS and cognitive decline. Presentation: 6/2/2024

7985 Insights into the Menopausal Transition: A Comparative Analysis of Hypothalamic Reproductive Aging in Women and a Mouse Model of Menopause

Abstract Disclosure: J.C. Bloom: None. S.A. Pereira: None. E. Torres Jimenez: None. D.C. Page: None. V.M. Navarro: None. Menopause onset is the major determinant of reproductive lifespan in women and is characterized by the decline in estrogen production from the ovary. While much of our current understanding of the menopause transition in humans comes from a series of observational longitudinal studies initiated in the 1980s and 1990s, the mechanisms by which reproductive aging impacts healthy brain aging remains a profoundly under-studied aspect of women’s health. The hypothalamus, a hub of homeostatic and temperature regulation, is highly sensitive to changes in sex steroid levels. Recently, activation of the neurokinin 3 receptor (NK3R) by neurokinin B (NKB) has been linked to the onset of vasomotor symptoms (VMS) during menopausal transition. NKB is secreted by hypothalamic Kisspeptin, NKB, Dynorphin (KNDy) neurons in response to decreasing estradiol levels. Here, we present a comparative study of the expression trajectories of the KNDy genes (KISS1, TAC3, PDYN, respectively) and NK3R (TACR3) in hypothalamic samples of humans across menopause and a mouse model of peri- and post-menopause (short- and long-term ovariectomy (OVX), respectively). RNA-sequencing data of human and mouse hypothalamic samples revealed a high correlation in the expression profile of the KNDy/NK3R genes between both species. Further investigation has revealed a highly conserved pool of genes in human and mouse hypothalami that correlate with TACR3 upon decline of circulating sex steroids. Thus, by examining conserved gene expression patterns across this critical reproductive period, we have been able to identify novel candidate targets involved in menopausal transition which may serve to better elucidate the biology of menopause-associated conditions affecting the brain, such as VMS and cognitive decline. Presentation: 6/2/2024

7772 A Study on Role of Anti-Mullerian Hormone and Inhibin B in 46,XY Disorders Of Sexual Development

Abstract Disclosure: N. Kudugunti: None. S. Bangaru: None. R.K. Sahay: None. Background: In pre-pubertal period, a major part of the testicular tissue is constituted by Sertoli cells for which AMH, Inhibin B are specific biomarkersHigh AMH, Inhibin B levels in the prepubertal period is via FSH stimulation, which is mistakenly considered to be silent due to its reduced activity Aim & Objectives: To assess AMH and Inhibin B measurements in the diagnostic workup of prepubertal children with different subtypes of 46,XY DSD and comparing with normal controls To assess Sertoli cell function with AMH and Inhibin B and to assess correlation between testosterone elevation after hCG stimulation, basal AMH and Inhibin B Patients and methods: Pilot study-Single centered, Cross-sectional Observational study. After ethical committee approval, 40 children with 46,XY DSD & 40 healthy age matched, boys as controls recruited after taking assent. All children with DSD underwent karyotyping, assessment of hCG stimulated testosterone, DHT and androstenedione. Basal AMH and inhibin B were measured in both cases and controls. Data were analysed using IBM SPSS version 25. Results: The mean age at presentation was 4.09 years.The diagnosis was made clinically and biochemically, genetic analysis done in few patients. Out of 40 cases, 26 had normal hCG stimulated testosterone of >100 ng/dl (17 cases were 5 alpha reductase type 2 deficiency [5αR2D], 9 cases were PAIS) & 14 had low hCG stimulated testosterone of <100 ng/dl (8 cases were 17βHSD3 deficiency, 4 cases were Partial gonadal dysgenesis [PGD], 2 cases were Vanishing testis syndrome). In the low testosterone group, mean AMH in 17βHSD3 deficiency-279.95 ng/ml, in PGD-31.16 ng/ml which is statistically significant in differentiating these disorders(p-0.002)& mean Inhibin B in 17βHSD3 deficiency-186.41 pg/ml, in PGD-35.95 pg/ml which is statistically significant in differentiating these disorders (p-0.007). In vanishing testis syndrome, AMH & Inhibin B were helpful in confirming the absent functioning testicular tissue Whereas in normal testosterone group, mean AMH in PAIS-235.65 ng/ml, in 5αR2D-289.08 ng/ml difference is not statistically significant(p-0.36)& mean Inhibin B in PAIS-204.50 pg/ml, in 5αR2D-190.91 pg/ml difference is not statistically significant(p-0.72) There was significant correlation between basal AMH and hCG stimulated testosterone (r=0.434; p-0.002), Inhibin B and hCG stimulated testosterone(r=0.438; p-0.001), AMH and Inhibin B(r=0.770; p<0.001). Conclusion: AMH and Inhibin B are valuable in differentiating PGD, 17βHSD3 deficiency in low hCG stimulated testosterone patients, but not helpful in differentiating PAIS, 5αR2D in normal hCG stimulated testosterone patients. Especially in PGD they may have a role with respect to fertility prospects and malignancy risk assessment. Presentation: 6/3/2024

9240 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p <0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

8039 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p <0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

9240 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p <0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

8039 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p <0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

Association of psychosocial factors with sleep quality among aging adults in India: Moderating role of functional limitations and negative feelings

ABSTRACT Sleep is one of the vital factors in physiological and psychological health and well-being. Good quality of sleep is essential for healthy aging and functioning. However, there is a lack of understanding of the role of psychosocial factors in sleep quality among aging adults in India. Further, with an increasing proportion of aging population in India, it becomes critical to understand the determinants of sleep quality among aging adults. The present study also explored the moderating role of negative feelings and functional limitations between psychosocial factors and sleep quality. The study used secondary data from the Longitudinal Ageing Study in India (LASI) wave –1 (2017–2018). A sample of 16,152 middle-aged and older adults was included in the study. Descriptive statistics, multiple regression, and moderation analysis were conducted to get an insight into the impacts of the predictors on individuals’ sleep quality. The results of the study suggest lower everyday discrimination (β = -.065, 99% CI [-.083, -.048]), good life satisfaction (β = -.009, 95% CI [-.017, -.002]), lower negative feelings (β = .1, 99% CI [.091, .109]), and functional limitations (β = .22, 99% CI [.197, .244]) was associated with good sleep quality. Furthermore, negative feelings and functional limitations acted as moderators in unadjusted models, while only functional limitations acted as moderators between life satisfaction and sleep quality, spirituality, and sleep quality in the fully adjusted model. This study implies the need for various measures to improve the sleep quality of aging adults by focusing on physical, psychological, and social domains of health and well-being.

Longitudinal autophagy profiling of the mammalian brain reveals sustained mitophagy throughout healthy aging.

Mitophagy neutralizes mitochondrial damage, thereby preventing cellular dysfunction and apoptosis. Defects in mitophagy have been strongly implicated in age-relatedneurodegenerative disorders such as Parkinson's and Alzheimer's disease. While mitophagy decreases throughout the lifespan of short-lived model organisms, it remains unknown whether such a decline occurs in the aging mammalian brain-a question of fundamental importance for understanding cell type- and region-specific susceptibility to neurodegeneration. Here, we define the longitudinal dynamics of basal mitophagy and macroautophagy across neuronal and non-neuronal cell types within the intact aging mouse brain in vivo. Quantitative profiling of reporter mouse cohorts from young to geriatric ages reveals cell- and tissue-specific alterations in mitophagy and macroautophagy between distinct subregions and cell populations, including dopaminergic neurons, cerebellar Purkinje cells, astrocytes, microglia and interneurons. We also find that healthy aging is hallmarked by the dynamic accumulation of differentially acidified lysosomes in several neural cell subsets. Our findings argue against any widespread age-related decline in mitophagic activity, instead demonstrating dynamic fluctuations in mitophagy across the aging trajectory, withstrong implications for ongoing theragnostic development.

Bats as instructive animal models for studying longevity and aging.

Bats (order Chiroptera) are emerging as instructive animal models for aging studies. Unlike some common laboratory species, they meet a central criterion for aging studies: they live for a long time in the wild or in captivity, for 20, 30, and even >40 years. Healthy aging (i.e., healthspan) in bats has drawn attention to their potential to improve the lives of aging humans due to bat imperviousness to viral infections, apparent low rate of tumorigenesis, and unique ability to repair DNA. At the same time, bat longevity also permits the accumulation of age-associated systemic pathologies that can be examined in detail and manipulated, especially in captive animals. Research has uncovered additional and critical advantages of bats. In multiple ways, bats are better analogs to humans than are rodents. In this review, we highlight eight diverse areas of bat research with relevance to aging: genome sequencing, telomeres, and DNA repair; immunity and inflammation; hearing; menstruation and menopause; skeletal system and fragility; neurobiology and neurodegeneration; stem cells; and senescence and mortality. These examples demonstrate the broad relevance of the bat as an animal model and point to directions that are particularly important for human aging studies.

Topical Platelet Exosomes Reduce Senescence Signaling in Human Skin: An Exploratory Prospective Trial.

Cellular senescence, an irreversible cell cycle arrest with secretory phenotype, is a hallmark of skin aging. Regenerative exosome-based approaches, such as topical human platelet extract (HPE), are emerging to target age-related skin dysfunction. To evaluate the cellular and molecular effects of topical HPE for skin rejuvenation after 12 weeks of twice daily use. Skin biopsies were obtained for histological evaluation of senescence markers, p16INK4a and p21CIP1/WAF1. Telomere-associated foci, coassociation of telomeres, and DNA damage marker, γH2AX, were assessed. RNA sequencing evaluated senescence associated secretory phenotype (SASP) and extracellular matrix pathways. p16INK4a and p21CIP1/WAF1 staining in senescent skin cells revealed low and high expression subgroups that did not correspond to chronological age. Topical HPE significantly reduced high p16INK4a cells in the dermis (p = .02). There was also a decrease in telomere damage after topical HPE (p = .03). In patients with high senescent cells at baseline, there was a 40% reduction in proinflammatory SASP. Extracellular matrix remodeling pathways, including collagen and elastic fibers, were up-regulated. Topical HPE, applied on intact skin, reduced senescence signaling and senescence-associated telomere damage after 12 weeks of twice daily use, targeting a path for skin longevity or healthy skin aging.

Cognitive synaptopathy: synaptic and dendritic spine dysfunction in age-related cognitive disorders.

Cognitive impairment is a leading component of several neurodegenerative and neurodevelopmental diseases, profoundly impacting on the individual, the family, and society at large. Cognitive pathologies are driven by a multiplicity of factors, from genetic mutations and genetic risk factors, neurotransmitter-associated dysfunction, abnormal connectomics at the level of local neuronal circuits and broader brain networks, to environmental influences able to modulate some of the endogenous factors. Otherwise healthy older adults can be expected to experience some degree of mild cognitive impairment, some of which fall into the category of subjective cognitive deficits in clinical practice, while many neurodevelopmental and neurodegenerative diseases course with more profound alterations of cognition, particularly within the spectrum of the dementias. Our knowledge of the underlying neuropathological mechanisms at the root of this ample palette of clinical entities is far from complete. This review looks at current knowledge on synaptic modifications in the context of cognitive function along healthy ageing and cognitive dysfunction in disease, providing insight into differential diagnostic elements in the wide range of synapse alterations, from those associated with the mild cognitive changes of physiological senescence to the more profound abnormalities occurring at advanced clinical stages of dementia. I propose the term "cognitive synaptopathy" to encompass the wide spectrum of synaptic pathologies associated with higher brain function disorders.

Molecular composition of skeletal muscle in infants and adults: a comparative proteomic and transcriptomic study

To gain a deeper understanding of skeletal muscle function in younger age and aging in elderly, identification of molecular signatures regulating these functions under physiological conditions is needed. Although molecular studies of healthy muscle have been conducted on adults and older subjects, there is a lack of research on infant muscle in terms of combined morphological, transcriptomic and proteomic profiles. To address this gap of knowledge, we performed RNA sequencing (RNA-seq), tandem mass spectrometry (LC–MS/MS), morphometric analysis and assays for mitochondrial maintenance in skeletal muscle biopsies from both, infants aged 4–28 months and adults aged 19–65 years. We identified differently expressed genes (DEGs) and differentially expressed proteins (DEPs) in adults compared to infants. The down-regulated genes in adults were associated with functional terms primarily related to sarcomeres, cellular maintenance, and metabolic, immunological and developmental processes. Thus, our study indicates age-related differences in the molecular signatures and associated functions of healthy skeletal muscle. Moreover, the findings assert that processes previously associated solely with aging are indeed part of development and healthy aging. Hence, combined findings of this study also indicate that age-dependent controls are crucial in muscle disease studies, as otherwise the comparative results may not be reliable.

Integrative nursing interventions: knowledge, attitudes and practice in home nursing services in Germany-a quantitative and qualitative online survey.

Integrative nursing interventions (INI) play a significant role in healthcare, particularly in the prevention and treatment of chronic diseases. Integrating evidence-based INI into healthcare aligns with global initiatives such as the WHO's Decade of Healthy Aging 2020-2030. Many INI are low-threshold practices, empowering patients to independently manage health. However, the extent to which INI are used by home-care nursing-services (HNS) remains largely unknown. This study aims to explore the field of INI in German HNS regarding nurses' use of INI as well as attitudes, subjective knowledge, and information needs on the subject. A cross-sectional anonymous online survey with 29 Likert scale items and two open-ended questions was conducted between April 2023 and July 2023. The survey targeted nurse managers of HNS in Baden-Württemberg, Germany. Descriptive analysis was performed for quantitative data, while content analysis according to Kuckartz was applied to analyze open-ended text responses. In total, n = 68 out of n = 1,331 HNS took part in the survey yielding a response rate of 5.1%. Their overall attitude toward INI was clearly positive (10-point Likert scale M ± SD: 8.37 ± 2.22). The average self-assessed knowledge level about INI was moderate (M ± SD: 5.39 ± 2.76). Almost half of the participants (45.6%) declared to incorporate INI in patient care. Most participants (84.2%) lacked employees with additional qualifications in INI. The INI used most were medicinal herbal teas (61%), compresses (57%), and aromatherapy (48%). Acupressure showed the greatest disparity between actual use in participating HNS (4.3%) and interest in further education (61%). The most common symptoms for which INI are used are pain, respiratory problems, anxiety, and palliative care. The main challenges reported for the use of INI in HNS are financial aspects, qualification and limited resources (staff and time). This exploratory study provides the first insights into nurses' attitudes, self-assessed knowledge, and utilization of INI in German HNS. Overall response rate was low (5.1%), therefore, the results should be interpreted with caution. Urgent action is needed to address financial aspects and further education on INI, to promote integration of INI in HNS to the best possible extent.

Assessing the adequacy of health facilities for the aging population in Indian cities

India, a developing country and currently the most populous nation, has been experiencing a rapid and unpredictable increase in the proportion of its older population. The healthcare system is already struggling to meet the needs of the current population, and the rising number of older adults is expected to further strain resources. Therefore, this study aimed to investigate the distribution of the older population in Indian cities and their access to advanced health facilities. The study uses data from Census of India, 2011, which is the latest census data available. A Health Facilities Index was developed to assess the availability of health facilities, and a geospatial approach was adopted to determine aging patterns and access to health facilities across cities. Despite similar aging trends, health infrastructure was unevenly distributed across cities. The study revealed that advanced health facilities were concentrated in specific areas, primarily metropolitan cities, whereas smaller cities lacked adequate health facilities and accessibility. Therefore, improving health infrastructure in smaller cities to match that in larger ones should be prioritized. The findings highlight a notable infrastructure gap in Indian cities, which presents a significant challenge to achieving healthy aging in the country.

6-Year Follow-Up of a World Record Breaking Master Marathon Runner.

Endurance performance declines with advancing age. Of the three main physiological factors that determine endurance running performance (maximal oxygen consumption [V̇O2max], lactate threshold, and running economy [RE]), V̇O2max appears to be most affected by age. While endurance performance declines with age, recently, endurance performance has rapidly improved in master athletes as the number of master athletes competing in endurance events has increased. Master athletes represent an intriguing model to study healthy aging. In this case study, we reassessed the physiological profile of a 76-year-old distance runner who broke the marathon world record for men over 70 years of age in 2018. This runner was tested a few months before breaking the world record and retested in 2024. Between 2018 and 2024, his marathon running velocity decreased significantly. Therefore, the purpose of this case study was to determine the physiological changes that explain his performance decline. RE remained similar to 2018, and while there was not a clear breakpoint in blood lactate, he still likely runs marathons at a high percentage (~90%) of his V̇O2max. However, V̇O2max declined by 15.1%. HRmax declined by 3.2% and maximal O2 pulse declined by 12.4%, suggesting that maximal stroke volume and/or arteriovenous O2 difference decreased. Altogether, although this marathoner continues to compete at an elite level, his performance has declined since his record-breaking marathon due to a reduction in V̇O2max. This is likely caused by reductions in maximal stroke volume and/or arteriovenous O2 difference. We speculate that these changes reflect primarily age-related processes.

β-asarone protects against age-related motor decline via activation of SKN-1/Nrf2 and subsequent induction of GST-4

Decelerating motor decline is important for promoting healthy aging in the elderly population. Acorus tatarinowii Schott is a traditional Chinese medicine that contains β-asarone as a pharmacologically active constituent. We found that β-asarone can decelerate motor decline in various age groups of Caenorhabditis elegans, while concurrently prolonging their lifespan and modulating synaptic transmission. To understand the mechanisms of its efficacy in motor improvement, we investigated and discovered that mitochondrial fragmentation, a marker for aging, is delayed after β-asarone treatment. Moreover, their efficacy is blocked by dysfunctional mitochondria. Corresponding to their role in regulating mitochondrial homeostasis, we found that SKN-1/Nrf2 and GST-4 are critical in the β-asarone treatment, and they appear to be activated via the insulin/IGF-1 signaling pathway. Well-developed intestinal microvilli are required for this process. Our study demonstrates the efficacy and mechanism of β-asarone treatment in age-related motor decline, contributing to the discovery of drugs for achieving healthy aging.

Harnessing gut microbiota for longevity: Insights into mechanisms and genetic manipulation

AbstractThe gut microbiota is pivotal in maintaining health, with most microorganisms being beneficial, except for a few pathogens. Emerging evidence suggests a link between the gut microbiome and aging, hinting at its potential role in longevity. However, understanding the relationship is challenging due to the microbiota's complexity. This perspective summarizes the mechanisms by which gut microbes regulate host lifespan and explores genetic manipulation strategies to promote healthy aging in the elderly.

Gait speed in older adults: exploring the impact of functional, physical and social factors

Purpose: With age there is a neuromuscular and cognitive decline that impacts on functional ability. One of the most characteristic and easily recognisable signs of this decline is a decrease in usual gait speed. For older adults, gait speed is a non-invasive indicator of health and functional status and is regarded as a vital sign. As it predicts various conditions later in life, measuring usual walking speed is crucial in the clinical setting. Therefore, analysing and determining the association between walking speed and the impact of functional and socio-economic variables may facilitate the prevention of associated health problems and the maintenance of physical function in older adults. This study aims to identify the key factors that influence walking speed in older adults, as well as to examine the influence of socio-economic status on walking speed. Methods: A total of 1253 older adults (89.5% women) with a mean age of 78.1 ± 5.8 voluntarily participated in this descriptive cross-sectional study, which examines the results of functional capacity tests and socioeconomic data in older adults. To assess physical function, SPPB tests (chair stand test, balance tests, gait speed test), manual grip strength, muscle quality index, and power were conducted, in addition to measuring body composition and socioeconomic status. Results: The final regression model showed that gait speed was significantly partially explained (R2=0.35; p<0.01) by the socioeconomic environment, age, balance, and relative power. At the same time, belonging to a higher socio-economic environment is linked to lower relative power (p<0.01; η2=0.07). Conclusions: Exploring the factors that affect walking speed in older adults, this study highlights that age, relative power and balance are significant determinants. These clinical markers provide crucial information for designing personalized and effective interventions to promote healthy aging. Keywords: Frailty, gait speed, elderly, relative power, socioeconomic status.