Aging Process Research Articles

Focus on senescence: Clinical significance and practical applications.

The older population is increasing worldwide, and life expectancy is continuously rising, predominantly thanks to medical and technological progress. Healthspan refers to the number of years an individual can live in good health. From a gerontological viewpoint, the mission is to extend the life spent in good health, promoting well-being and minimizing the impact of aging-related diseases to slow the aging process. Biologically, aging is a malleable process characterized by an intra- and inter-individual heterogeneous and dynamic balance between accumulating damage and repair mechanisms. Cellular senescence is a key component of this process, with senescent cells accumulating in different tissues and organs, leading to aging and age-related disease susceptibility over time. Removing senescent cells from the body or slowing down the burden rate has been proposed as an efficient way to reduce age-dependent deterioration. In animal models, senotherapeutic molecules can extend life expectancy and lifespan by either senolytic or senomorphic activity. Much research shows that dietary and physical activity-driven lifestyle interventions protect against senescence. This narrative review aims to summarize the current knowledge on targeting senescent cells to reduce the risk of age-related disease in animal models and their translational potential for humans. We focused on studies that have examined the potential role of senotherapeutics in slowing the aging process and modifying age-related disease burdens. The review concludes with a general discussion of the mechanisms underlying this unique trajectory and its implications for future research.

Plasticity, heterogeneity, and multifunctionality of hepatic stellate cells in liver pathophysiology.

HSCs, the resident pericytes of the liver, have consistently been at the forefront of liver research due to their crucial roles in various hepatic pathological processes. Prior literature often depicted HSCs in a binary framework, categorizing them as either quiescent or activated. However, recent advances in HSC research, particularly the advent of single-cell RNA-sequencing, have revolutionized our understanding of these cells. This sophisticated technique offers an unparalleled, high-resolution insight into HSC populations, uncovering a spectrum of diversity and functional heterogeneity across various physiological states of the liver, ranging from liver development to the liver aging process. The single-cell RNA-sequencing revelations have also highlighted the intrinsic plasticity of HSCs and underscored their complex roles in a myriad of pathophysiological processes, including liver injury, repair, and carcinogenesis. This review aims to integrate and clarify these recent discoveries, focusing on how the inherent plasticity of HSCs is central to their dynamic roles both in maintaining liver homeostasis and orchestrating responses to liver injury. Future research will clarify whether findings from rodent models can be translated to human livers and guide how these insights are harnessed to develop targeted therapeutic interventions.

Brain structural covariances in the ageing brain in the UK Biobank.

The morphologic properties of brain regions co-vary or correlate with each other. Here we investigated the structural covariances of cortical thickness and subcortical volumes in the ageing brain, along with their associations with age and cognition, using cross-sectional data from the UK Biobank (N = 42,075, aged 45-83 years, 53% female). As the structural covariance should be estimated in a group of participants, all participants were divided into 84 non-overlapping, equal-sized age groups ranging from the youngest to the oldest. We examined 84 cortical thickness covariances and subcortical covariances. Our findings include: (1) there were significant differences in the variability of structural covariance in the ageing process, including an increased variance, and a decreased entropy. (2) significant enrichment in pairwise correlations between brain regions within the occipital lobe was observed in all age groups; (3) structural covariance in older age, especially after the age of around 64, was significantly different from that in the youngest group (median age 48 years); (4) sixty-two of the total 528 pairs of cortical thickness correlations and 10 of the total 21 pairs of subcortical volume correlations showed significant associations with age. These trends varied, with some correlations strengthening, some weakening, and some reversing in direction with advancing age. Additionally, as ageing was associated with cognitive decline, most of the correlations with cognition displayed an opposite trend compared to age associated patterns of correlations.

Thermo-mechanical aging of carbon-black reinforced styrene-butadiene rubber under cyclic-loading

PurposeThe research aims to investigate the impact of thermo-mechanical aging on SBR under cyclic-loading. By conducting experimental analyses and developing a 3D finite element analysis (FEA) model, it seeks to understand chemical and physical changes during aging processes. This research provides insights into nonlinear mechanical behavior, stress softening and microstructural alterations in SBR compounds, improving material performance and guiding future strategies.Design/methodology/approachThis study combines experimental analyses, including cyclic tensile loading, attenuated total reflection (ATR), spectroscopy and energy-dispersive X-ray spectroscopy (EDS) line scans, to investigate the effects of thermo-mechanical aging (TMA) on carbon-black (CB) reinforced styrene-butadiene rubber (SBR). It employs a 3D FEA model using the Abaqus/Implicit code to comprehend the nonlinear behavior and stress softening response, offering a holistic understanding of aging processes and mechanical behavior under cyclic-loading.FindingsThis study reveals significant insights into SBR behavior during thermo-mechanical aging. Findings include surface roughness variations, chemical alterations and microstructural changes. Notably, a partial recovery of stiffness was observed as a function of CB volume fraction. The developed 3D FEA model accurately depicts nonlinear behavior, stress softening and strain fields around CB particles in unstressed states, predicting hysteresis and energy dissipation in aged SBRs.Originality/valueThis research offers novel insights by comprehensively investigating the impact of thermo-mechanical aging on CB-reinforced-SBR. The fusion of experimental techniques with FEA simulations reveals time-dependent mechanical behavior and microstructural changes in SBR materials. The model serves as a valuable tool for predicting material responses under various conditions, advancing the design and engineering of SBR-based products across industries.

Human skeletal muscle aging atlas.

Skeletal muscle aging is a key contributor to age-related frailty and sarcopenia with substantial implications for global health. Here we profiled 90,902 single cells and 92,259 single nuclei from 17 donors to map the aging process in the adult human intercostal muscle, identifying cellular changes in each muscle compartment. We found that distinct subsets of muscle stem cells exhibit decreased ribosome biogenesis genes and increased CCL2 expression, causing different aging phenotypes. Our atlas also highlights an expansion of nuclei associated with the neuromuscular junction, which may reflect re-innervation, and outlines how the loss of fast-twitch myofibers is mitigated through regeneration and upregulation of fast-type markers in slow-twitch myofibers with age. Furthermore, we document the function of aging muscle microenvironment in immune cell attraction. Overall, we present a comprehensive human skeletal muscle aging resource ( https://www.muscleageingcellatlas.org/ ) together with an in-house mouse muscle atlas to study common features of muscle aging across species.

A study to assess the prevalence of menopausal symptoms and its impact on quality of life in the menopausal women in a selected Urban community, Kolkata, West Bengal

Menopause is the end of menstruation. Menopause is cessation of menstruation for 12 months or a period that equivalent to three previous cycles or as time of cessation of ovarian function resulting in permanent amenorrhea. Menopause is a part of a women’s natural ageing process when lower level of estrogen & progesterone is produced by ovaries. This cross-sectional study was conducted on a total of 400 women in the age group of 45-50 years in a selected urban community, Kolkata, West Bengal in 2020. Menopause Specific Quality of Life scale was used to assess the prevalence of menopausal symptoms and its impact. Data analysis was performed calculating mean, frequency and percentage and chisquare. Among the vasomotor symptoms prevalence of sweating was maximum (98%), among psychological symptoms anxiety and nervousness was the maximum prevalent symptoms(98%), most prevalent physical symptom was lack of energy (89.25%). Vasomotor symptoms had mild moderate and severe impact on quality of life where the other symptoms had mild and moderate impact on quality of life. Menopausal symptoms had significant association with socio demographic variables. The results support the popular belief that menopause causes vasomotor, physical and psychological problems. From the findings of the present study it can be concluded that almost all areas or domains evaluated were impaired in menopausal women but the vasomotor and psychological symptoms affects women’s quality of life more than the physical and sexual symptoms of menopause

Probing Interfacial Aging of Model Adhesion Joints under a Hygrothermal Environment at a Molecular Level.

Generally, for adhesive joints, the polar water molecules in humid environments can have a critical effect on the interfacial structures and structural evolution adjacent to the solid substrates. Regarding this, it is still a big challenge to detect and understand the interfacial hygrothermal aging process at the molecular level in real time and in situ. In this study, to trace the interfacial hygrothermal aging process of a classical epoxy formula containing diglycidyl ether of biphenyl A (DGEBA) and 2,2'-(ethylenedioxy) diethylamine (EDDA) with sapphire and fused silica in a typical hygrothermal environment (85 °C and 85% RH), sum frequency generation (SFG) vibrational spectroscopy was used to probe the molecular-level interfacial structural change over the time. The structural evolution dynamics at the buried epoxy/sapphire and epoxy/silica interfaces upon hygrothermal aging were revealed directly in situ. The interfacial delamination during hygrothermal aging was also elucidated from the molecular level. Upon hygrothermal aging, the interfacial CH signals, such as the ones from methyl, methylene, and phenyl groups, decreased significantly and the water OH signals increased substantially, indicating the water molecules had diffused into the interfaces and destroyed the original interactions between the epoxy formula and the substrates. Further analysis indicates that when the integrated signals in the CH range declined to their minimum and leveled off, the interfacial delamination happened. The tensile experiment proved the validity of these spectroscopic experimental results. Our study provides first-hand and molecular-level evidence on a direct correlation between the diffusion of the surrounding water molecules into the interface and the evolution/destruction of the interfacial structures during hygrothermal aging. More importantly, it is proved, SFG can be developed into a powerful tool to noninvasively reveal the local interfacial delamination in real time and in situ under extreme hygrothermal conditions, complemented by the mechanic test.

Performance evaluation of aged asphalt rejuvenated with waste cooking oil on rheological and chemical characristics

Abstract This study investigates the influence of varying aging processes on the rheological behavior and microscopic features of bio-based recycled asphalt, focusing on the utilization of Waste Cooking Oil (WCO) as a rejuvenator. The research evaluates the rheological and fatigue characteristics of the modified binder, alongside a detailed microscopic analysis to determine the molecular composition changes in both aged and recycled asphalt. The incorporation of WCO was found to compromise rutting performance slightly, yet significantly enhance fatigue resistance and reduce susceptibility to low-temperature cracking. With the progression of aging, an increased dosage of WCO effectively mitigated the negative impacts, bringing the molecular composition and functional groups of the aged asphalt closer to that of the original material. Despite these improvements, a full restoration to the asphalt’s original properties remained elusive. These findings underscore the potential of waste bio-oil as a sustainable resource for enhancing the durability and environmental friendliness of asphalt pavements.

Labour market gender gaps and childcare policies in countries with different social investment strategies

AbstractWe study the role of formal and informal childcare within the ECEC policies for gender employment and pay gaps, considering the life course stages distinctive for childcare tasks. The ECEC policies are framed within the types of social investment strategies identified in the EU countries to picture developments in social investments after 2005. The aggregated EU‐SILC data from 2005 to 2019 for 27 European countries have been used in the panel regression models to uncover how the caring arrangements influence labour market gendered outcomes of women at different ages (15–24, 25–49, 50–65). We find that better provision and use of early education and childcare not only contribute to early investment in human capital but it also facilitates mothers' employment and thus contributes to lowering gender employment and pay gaps. However, better coverage of care for children older than 3 years old results in negative employment effects for grandmothers. These effects vary also across countries, depending on their overall institutional setting depicted by the types of social investment strategies distinguished. Consequently, the ECEC agenda should be extended by addressing the employment of women at the pre‐retirement age. It is crucial not only for reducing gender gap in employment and pay but also in the light of challenges generated by demographic developments—the labour force shrinking and the population ageing processes.

ВЛИЯНИЕ ТЕМПЕРАТУРЫ И ПРОЦЕССОВ СТАРЕНИЯ МАТЕРИАЛА НА СИЛОВЫЕ ХАРАКТЕРИСТИКИ ПОЛИМЕРНЫХ ПОГЛОЩАЮЩИХ АППАРАТОВ ВАГОНОВ

Improving the dynamic qualities, traffic safety and increasing the inter-repair mileage of cars are urgent tasks of car-building industry. The most dangerous loads acting on the car are longitudinal loads during emergency driving modes, to reduce which inter-car shock absorbers (absorbing devices) are provided; their effectiveness must be ensured throughout the whole car life. The performance of polymer car absorbing devices depends primarily on the durability of the polymer, which is a kinetically activated process accelerated by repeated deformations and elevated temperature. The mechanism of the material ageing process depends on the structure of the material. Based on experimental laboratory studies and comparative field tests, ageing of elastomers of different classes have been identified, the dependences of the power characteristics of R-5P absorbing apparatus with two types of solid elastomer (based on rubber and a mixture of elastic thermoplastic with polyvinyl chloride plastic) have been constructed at normal and low temperatures, as well as after 6 years of operation. Recommendations are given to increase the resistance to crystallization and to ageing of polymer elements of absorbing devices. It is advisable to use the characteristics obtained in the paper when modeling the operation of absorbing devices with a solid elastomer, taking into account the operating time.

The role of the immunosuppressive PD-1/PD-L1 checkpoint pathway in the aging process and age-related diseases.

The accumulation of senescent cells within tissues is a hallmark of the aging process. Senescent cells are also commonly present in many age-related diseases and in the cancer microenvironment. The escape of abnormal cells from immune surveillance indicates that there is some defect in the function of cytotoxic immune cells, e.g., CD8+ T cells and natural killer (NK) cells. Recent studies have revealed that the expression of programmed death-ligand 1 (PD-L1) protein is abundantly increased in senescent cells. An increase in the amount of PD-L1 protein protects senescent cells from clearance by the PD-1 checkpoint receptor in cytotoxic immune cells. In fact, the activation of the PD-1 receptor suppresses the cytotoxic properties of CD8+ T and NK cells, promoting a state of immunosenescence. The inhibitory PD-1/PD-L1 checkpoint pathway acts in cooperation with immunosuppressive cells; for example, activation of PD-1 receptor can enhance the differentiation of regulatory T cells (Treg), myeloid-derived suppressor cells (MDSC), and M2 macrophages, whereas the cytokines secreted by immunosuppressive cells stimulate the expression of the immunosuppressive PD-L1 protein. Interestingly, many signaling pathways known to promote cellular senescence and the aging process are crucial stimulators of the expression of PD-L1 protein, e.g., epigenetic regulation, inflammatory mediators, mTOR-related signaling, cGAS-STING pathway, and AhR signaling. It seems that the inhibitory PD-1/PD-L1 immune checkpoint axis has a crucial role in the accumulation of senescent cells and thus it promotes the aging process in tissues. Thus, the blockade of the PD-1/PD-L1 checkpoint signaling might be a potential anti-aging senolytic therapy. KEY MESSAGES: Senescent cells accumulate within tissues during aging and age-related diseases. Senescent cells are able to escape immune surveillance by cytotoxic immune cells. Expression of programmed death-ligand 1 (PD-L1) markedly increases in senescent cells. Age-related signaling stimulates the expression of PD-L1 protein in senescent cells. Inhibitory PD-1/PD-L1 checkpoint pathway suppresses clearance of senescent cells.

A step-by-step guide to ageing octopus

Global octopus catch has doubled over the past four decades and is likely to grow in importance as many key fisheries continue to decline. Lack of age data is a critical limitation in assessing the resource status of octopus. Over the past ~30 years, studies have investigated various methods to age octopus, with some methods better suited to certain species than others. However, only a small number of researchers have the hands-on knowledge to execute these methods in the laboratory. Here, we present the first step-by-step guide to ageing octopus, as well as a decision tool, which should enable readers to carry out the ageing process and make an informed decision on the most suitable method for their species. We provide guidance on age validation, increment analysis of both beaks and stylets, materials needed, as well as avenues for further research. We hope this guide will provide a starting point for researchers new to octopus ageing, and for those working with octopus species that have never been aged before. We also encourage researchers to use this guide as a forum for open discussion to support the ongoing development of effective octopus ageing methods.

Serum klotho levels and mortality patterns in frail individuals: unraveling the u-shaped association

BackgroundFrailty, a clinical syndrome intricately linked with the aging process, stands as a harbinger of numerous adverse outcomes, most notably mortality. This study aimed to elucidate the association between serum α-klotho concentration and mortality patterns, including all-cause and cause-specific mortality, in patients with frailty.MethodsThe study employed Cox proportional hazard models, smoothed curve fitting, and supplementary analyses, encompassing threshold effect analysis, subgroup and sensitivity analyses, to explore the relationship between α-klotho levels and mortality, including all-cause, CVD, and cancer-related mortality.ResultsAmong the 2,608 frail individuals (mean age: 60.78 [SD 10.48] years; 59.89% female), the mortality stood at 25.35% during a median follow-up period of 6.95 years. Both unadjusted and adjusted models revealed a significant inverse association between higher serum α-klotho levels and the risk of all-cause and CVD-related mortality ([mean(95% CI) 0.68 (0.55, 0.83)] for all-cause mortality; [mean(95% CI) 0.48 (0.32, 0.74)] for CVD-related mortality, all P for trend < 0.001). Notably, log2–klotho displayed a U-shaped correlation with all-cause mortality and cancer mortality, characterized by thresholds of 9.48 and 9.55, respectively. The robustness of these findings was consistently supported by subgroup and sensitivity analyses.ConclusionThis study unveils a U shaped association between serum α-klotho levels and both all-cause and cancer-related mortality among middle-aged and elderly individuals with frailty in the United States. The identified serum α-klotho thresholds, at 714.8 pg/ml for all-cause mortality and 750.6 pg/ml for cancer-related mortality, hold promise as potential targets for interventions aimed at mitigating the risks of premature death and cancer within this vulnerable population.

Role of sirtuins in epigenetic regulation and aging control

Advances in modern healthcare in developed countries make it possible to extend the human lifespan, which is why maintaining active longevity is becoming increasingly important. After the sirtuin (SIRT) protein family was discovered, it started to be considered as a significant regulator of the physiological processes associated with aging. SIRT has deacetylase, deacylase, and ADP­ribosyltransferase activity and modifies a variety of protein substrates, including chromatin components and regulatory proteins. This multifactorial regulatory system affects many processes: cellular metabolism, mitochondrial functions, epigenetic regulation, DNA repair and more. As is expected, the activity of sirtuin proteins affects the manifestation of classic signs of aging in the body, such as cellular senescence, metabolic disorders, mitochondrial dysfunction, genomic instability, and the disruption of epigenetic regulation. Changes in the SIRT activity in human cells can also be considered a marker of aging and are involved in the genesis of various age­dependent disorders. Additionally, experimental data obtained in animal models, as well as data from population genomic studies, suggest a SIRT effect on life expectancy. At the same time, the diversity of sirtuin functions and biochemical substrates makes it extremely complicated to identify cause­and­effect relationships and the direct role of SIRT in controlling the functional state of the body. However, the SIRT influence on the epigenetic regulation of gene expression during the aging process and the development of disorders is one of the most important aspects of maintaining the homeostasis of organs and tissues. The presented review centers on the diversity of SIRT in humans and model animals. In addition to a brief description of the main SIRT enzymatic and biological activity, the review discusses its role in the epigenetic regulation of chromatin structure, including the context of the development of genome instability associated with aging. Studies on the functional connection between SIRT and longevity, as well as its effect on pathological processes associated with aging, such as chronic inflammation, fibrosis, and neuroinflammation, have been critically analyzed.

Longevity, Chronic Conditions and Ageing Dynamics: A Mathematical Reliability Perspective. Review

Background: Understanding the relationship between ageing and chronic diseases becomes crucial as global demographics shift towards an increasingly aged population. Aim: The primary objective of this review is to explore various theories of ageing and their implications for chronic disease prevalence in ageing populations. Methods: The study design entailed a comprehensive literature search to collect pertinent papers and theories on ageing, chronic diseases, and dependability theory. Various databases were employed to ascertain crucial insights and discoveries in this domain. Results: The review emphasises the complex and diverse factors involved in the ageing process and its connection to chronic diseases. We highlight the harmful effects of physical inactivity and sedentary behaviour on the health of older individuals. Moreover, we emphasise the importance of dependability theory in comprehending the development and progression of chronic health conditions among ageing populations. Conclusion: Increasing chronic illness prevalence in the ageing population is both a problem and a possibility for adequate care. Integrating reliability theory into comprehensive approaches may help us understand age-related chronic illnesses and create effective preventative measures. _________________________________________________________________________________________ Keywords: Ageing; Chronic diseases; Health span; Mathematical reliability theory; Population ageing; Preventive strategies

Internet Development, Population Aging and Urban-rural Income Gap: An Empirical Analysis Based on Provinces in China

Abstract This study utilizes panel data from Chinese provinces spanning 2013 to 2021 to establish a comprehensive evaluation index system for the level of Internet development. It investigates the impact of Internet development and its sub-dimensions on the urban-rural income gap and further examines the moderating effect of population aging. The findings suggest that Internet development can significantly improve the urban-rural income gap by increasing the farm and non-farm incomes of rural residents. Specifically, from a sub-dimension perspective, Internet infrastructure, commercial scale, and development potential play significant roles in narrowing the income gap, with substantial effects observed. Moreover, considering regional heterogeneity, the narrowing effect of the Internet on the urban-rural income gap in the Northeast, Central, and Western regions is significant and roughly equivalent, surpassing that of the Eastern region. Population aging leads to synchronous changes in the age structure of Internet users; the "silver-haired digital divide" impedes the elderly population's access to and use of the Internet, thereby inhibiting the shrinking effect of Internet development on the urban-rural income gap. Further investigation reveals that the imbalance in the urban-rural population aging process, with the degree of rural aging outpacing urban areas, is a significant factor contributing to this inhibitory effect. Keywords: Urban-rural Income Gap, Internet development, Population Aging, Moderating effect.

Compensatory brain activity pattern is not present in older adults during the n-back task performance—Findings based on EEG frequency analysis

IntroductionCognitive ability is one of the most important enablers for successful aging. At the same time, cognitive decline is a well-documented phenomenon accompanying the aging process. Nevertheless, it is acknowledged that aging can also be related to positive processes that allow one to compensate for the decline. These processes include the compensatory brain activity of older adults primarily investigated using fMRI and PET. To strengthen the cognitive interpretation of compensatory brain activity in older adults, we searched for its indicators in brain activity measured by EEG.MethodsThe study sample comprised 110 volunteers, including 50 older adults (60–75 years old) and 60 young adults (20–35 years old) who performed 1-back, 2-back, and 3-back tasks while recording the EEG signal. The study analyzed (1) the level of cognitive performance, including sensitivity index, the percentage of correct answers to the target, and the percentage of false alarm errors; (2) theta and alpha power for electrodes located in the frontal-midline (Fz, AF3, AF4, F3, F4, FC1, and FC2) and the centro-parietal (CP1, CP2, P3, P4, and Pz) areas.ResultsCognitive performance was worse in older adults than in young adults, which manifested in a significantly lower sensitivity index and a significantly higher false alarm error rate at all levels of the n-back task difficulty. Simultaneously, performance worsened with increasing task difficulty regardless of age. Significantly lower theta power in the older participants was observed at all difficulty levels, even at the lowest one, where compensatory activity was expected. At the same time, at this difficulty level, cognitive performance was worse in older adults than in young adults, which could reduce the chances of observing compensatory brain activity. The significant decrease in theta power observed in both age groups with rising task difficulty can reflect a declining capacity for efficient cognitive functioning under increasing demands rather than adapting to this increase. Moreover, in young adults, alpha power decreased to some extent with increasing cognitive demand, reflecting adaptation to them, while in older adults, no analogous pattern was observed.DiscussionIn conclusion, based on the results of the current study, the presence of compensatory activity in older adults cannot be inferred.

Evaluation of chemical components and quality in Xinhui Chenpi (Citrus reticulata ‘Chachi’) with two different storage times by GC–MS and UPLC

AbstractXinhui Chenpi (XHCP) is a well‐known type of Chenpi (CP) widely used as both a Chinese herb and a food ingredient. While previous studies have explored how the quality of CP changes over time, there has been limited research specifically on XHCP. This study aims to assess the chemical components and quality of XHCP based on total flavonoid content (TF), antioxidant activity (AA), and color value (CV) at two stages: freshly harvested (XHCP‐0Y) and after 3 years of storage (XHCP‐3Y). Thirty‐eight common volatile compounds were identified, and the content of 17 compounds among them, nine nonvolatile compounds, which included one alkaloid (synephrine), three phenolic acids (PA, protocatechuic acid, vanillic acid, and ferulic acid), and five flavonoids (narirutin, hesperidin, sinensetin, nobiletin, and tangeretin), were firstly detected by the newly developed gas chromatograph–mass spectrometer (GC–MS) and ultra‐performance liquid chromatography (UPLC) methods. Compared to XHCP‐0Y, the content of 17 volatile compounds and synephrine decreased in XHCP‐3Y to varying degrees, while the content of PA, five flavonoids, TF, AA, and CV increased. The reduction of dryness caused by volatile compounds and the enhancement of efficacy related to PA, flavonoids, and AA suggested improved quality of XHCP after 3 years of storage. The methods developed in this study show promise for evaluating the quality of XHCP during the aging process.

Clinical studies with drugs and biologics aimed at slowing or reversing normal aging processes—emerging results and future perspectives

Five families of investigational products are in clinical investigation to slow or reverse normal aging processes [longevity candidates, mesenchymal stem cells, senolytics drugs, sirtuin activators, and nicotinamide adenine dinucleotide (NAD)+ precursors]. The longevity candidates, vitamin D and metformin, appear to significantly reduce all-cause mortality and prolong life expectancy. This should be confirmed by interventional studies. The mesenchymal stem cell family is the most advanced in clinical trial development [phase 2b randomized controlled trial (RCT)]. An allogeneic bone marrow stem cell preparation (Lomecel-B) reduced locomotor frailty in older people. The improvement in locomotion was modest. In the future, attempts could be made to improve potency through a precondition or genetic modification of naive bone marrow stem cells. Autologous adipose stem cell-assisted fat grafting increased graft survival, facial volume, and skin quality. The association of the senolytic drugs dasatinib and quercetin was well tolerated, with low brain penetration of dasatinib and undetectable levels of quercetin. The sirtuin-1 activator resveratrol (combined with physical exercise) improved physical function in older adults with physical limitations. The NAD+ precursor nicotinamide riboside improved physical exercise performance. In conclusion, Lomecel-B is the most advanced agent in clinical trial development for normal aging processes (phase 2b for locomotion frailty), followed by resveratrol and nicotinamide riboside.

Resistance training's impact on blood biomarkers and cognitive function in older adults with low and high risk of mild cognitive impairment: a randomized controlled trial

BackgroundThe aging brain exhibits a neuroinflammatory state, driven partly by peripheral pro-inflammatory stimuli, that accelerates cognitive deterioration. A growing body of evidence clearly indicates that physical exercise partly alleviates neuroinflammation and positively affects the aging process and cognition. In this randomized controlled trial, we aimed to observe the effect of 12 weeks of resistance training (RT) on peripheral biomarker levels, cognitive function changes and their interrelationship, and explore differences in those exercise-induced changes in older adults with high risk of mild cognitive impairment (MCI) compared to older adults with low risk of MCI.MethodsFifty-two participants (aged 60–85 years old, 28 female) were randomly allocated to a 12 week lower limb RT program consisting of two training sessions per week or waiting list control group. The Montreal Cognitive Assessment (MoCA) was used to stratify participants screened as high (< 26/30) or low risk (≥ 26/30) of MCI. We assessed serum Interleukin 6 (IL-6), Insulin-like Growth Factor-1 (IGF-1), and Kynurenine (KYN) levels. Cognitive measurement consisted of and four subtests of Automated Neuropsychological Assessment Metrics (ANAM), the two-choice reaction time, go/no-go, mathematical processing, and memory search test.ResultsTwelve weeks of RT improved Go/No-go test results in older adults with high MCI risk. RT did not significantly affect blood biomarkers. However, IGF-1 level increases were associated with improvements in response time on the mathematical processing test in the exercise group, and IL-6 level increases were associated with improvements in response time on the memory search test in the total group of participants. Finally, KYN levels significantly differed between older adults with low and high MCI risk but no significant associations with performance were found.ConclusionOur study results suggest a different effect of RT on inhibitory control between older adults with low compared to high MCI risk. IGF-1 may play a role in the mechanism behind the cognitive benefit of RT and KYN may be a surrogate biomarker for neurodegeneration and cognitive decline.