Age-related Decline Research Articles

Examining the health effects of public transport use on older adults: A systematic review

Background and aimPublic transport use has been linked to several health benefits in the general population and is crucial for older adults’ mobility, due to an age-related decline in physical and cognitive capacity and mobility, particularly the ability to use other modes of transport. The objective of this systematic review is to determine what is known about the physical and mental health outcomes of public transport use of older adults and to identify remaining gaps in the literature. MethodsFive electronic databases were searched in April 2023, and then updated in January 2024: Pubmed, Scopus, Web of Science, Ageline and Transport Research International Documentation (TRID). Included were studies that were in English, contained a measure of public transport use as exposure, and any health outcome, including mental or physical health, physical or cognitive function, morbidity, or mortality, among people aged ≥60 years. ResultsOf a total of 2247 unique records that were screened, the full text of 20 was assessed for eligibility and 11 were identified as eligible. Citation search identified two additional studies, amounting to a total of 13 included studies. Significant health outcomes described in assessed studies were decreased obesity and depressive symptoms, and to a lesser extent increased gait speed and cognitive function. ConclusionsInitial evidence suggests a positive impact of public transport use on obesity, depressive symptoms, gait and cognitive function, although available research was limited in context and methodology. Further research should focus on determining causality between public transport use and health, and be conducted in more diverse contexts. Transport and urban planners, as well as policymakers, should consider the implications of public transport on the health and independence of older adults.

Minimising Harm and Managing Pain: Deprescribing Opioids in Older Adults.

Approximately one in three older adults (aged 65 years and over) experience pain, negatively impacting their quality of life. Opioid analgesics are commonly prescribed to manage pain; however, balancing the benefits and harms of these high-risk analgesics can be challenging for both healthcare professionals and patients. This is particularly true for older adults, as factors such as polypharmacy, age-related physiological changes and cognitive decline may impact upon opioid safety and efficacy. Deprescribing is the patient-centred process of reducing or discontinuing a medication that is no longer appropriate, or where the risks of continuation are deemed to outweigh the anticipated benefits. Opioid deprescribing has been proposed as a mechanism to reduce individual and societal opioid-related harm; however, to date, research has predominantly focused on the general adult population, rather than older adults. This current opinion aims to summarise the existing opioid deprescribing literature, discussing its applicability for older adults. Drawing on a non-systematic review of the literature, it identifies unique challenges and considerations for this population, highlights international initiatives to enhance opioid deprescribing in clinical practice and proposes future directions to advance the field.

'It's designed for someone who is not me': A reflexive thematic analysis of the unmet healthcare support needs in UK autistic adults aged 65 years and over.

Autistic people often face both physical and mental health challenges throughout their lives, which can lead to a higher risk of premature death due to health inequalities. However, we know very little about the healthcare experiences of autistic older adults. In this study, we talked with 19 autistic adults aged 65 years or above living in the United Kingdom. We found these main themes: (1) A lifetime of being misunderstood; (2) Autistic people falling between the gaps; (3) Processing autism diagnosis in later life; (4) Concerns about service pressures and scarce resources; (5) Lack of continuity of care, empathy and understanding; (6) Anxiety, alexithymia and sensory overload; and (7) Reduced social support and concerns for the future. Themes show that autistic older adults face unique healthcare access challenges because services don't consider their lifelong experiences of social exclusion. Participants also worried about age-related decline coupled with reduced social support, which makes it harder for them to get support. To address these challenges, healthcare services should provide more targeted support, make policies and funding consistent, and improve healthcare provision by providing staff training. Importantly, they must also speak with autistic older adults so they can advocate for their current and future care.

Age-related decline in cardiac lymphatic vessels causes cardiac edema and macrophage accumulation

Abstract As life expectancy has significantly increased, age-related diseases, particularly cardiovascular diseases, have become a primary global cause of death. Aging has multiple effects on the heart and is one major risk factor for cardiovascular diseases. The microcirculation has been extensively studied in this context. However, the contribution of the lymphatic vasculature, which is responsible for draining excessive tissue fluid and immune cells, to age-related pathologies is currently unknown. To address the effect of aging on lymphatics, we examined lymphatic capillary density using LYVE1 and PDPN staining in old (>20 months) and young (3 months) mouse hearts. Aging induced a significant reduction in lymphatic vessel density in the sub-endocardial and –epicardial area of aged left ventricles, in both genders (0.28±0.08 fold and 0.68±0.03 fold; p<0.05), while the right ventricle showed no change. Notably, dilation of (pre-) collector lymphatics was observed in in old hearts, indicating, together with the lymphatic vessel reduction, a lymphatic drainage dysfunction. Indeed, cardiac aging was accompanied by increased numbers of CD68+ macrophages, accumulation of the plasma protein fibrinogen and amyloid into the interstitial space. Moreover, we observed a significant increase in tissue oedema in the aged hearts (p<0.05). The decline in lymphatic vessels was associated with a reduced expression of Vegfc (0.72±0.04 fold; p<0.005), a major lymphatic growth factor, in 20-month-old mouse hearts compared to their 3-month-old counterparts. To establish a causal link between lymphatic dysfunction and age-related cardiac changes, we examined hearts from 3-month-old Flt4;Prox1-CreERT2 mice, that have defective lymphatic vessels. Also these mice, despite their young age, displayed fibrinogen (1.32±0.08 fold; p<0.05) and CD68+ macrophage (1.58±0.08 fold; p<0.05) accumulation compared to wildtype littermates. Apart from these, other age-related changes, such as tendency to cardiac hypertrophy, were also observed; this is currently under further investigation. Likewise, blocking VEGFC signaling in young mice by overexpressing the soluble form of Flt4 impaired cardiac lymphatic capillary density (0.62±0.06 fold; p<0.01), leading to increased macrophage and fibrinogen accumulation (1.69±0.09 fold, 4.60±0.30 fold; p<0.001), suggesting that a decline of lymphatics induces some of the age-associated pathologies. Finally, we addressed whether restoring Vegfc expression in old mice can rescue age-related cardiac impairment. Overexpressing Vegfc via AAV9 in aged mice restored cardiac lymphatic density by 3-fold and reduced CD68+ macrophage density by 1.6-fold, without effect on fibrinogen accumulation. In conclusion, our study demonstrates an age-related reduction in left ventricular lymphatic density, cardiac edema and inflammation. Vegfc overexpression prevented the age-dependent decline of lymphatic vasculature and reduced cardiac inflammation.

Ageing leads to selective type II myofibre deterioration and denervation independent of reinnervative capacity in human skeletal muscle.

Age-related loss of muscle mass and function is underpinned by changes at the myocellular level. However, our understanding of the aged muscle phenotype might be confounded by factors secondary to ageing per se, such as inactivity and adiposity. Here, using healthy, lean, recreationally active, older men, we investigated the impact of ageing on myocellular properties in skeletal muscle. Muscle biopsies were obtained from young men (22±3years, n=10) and older men (69±3years, n=11) matched for health status, activity level and body mass index. Immunofluorescence was used to assess myofibre composition, morphology (size and shape), capillarization, the content of satellite cells and myonuclei, the spatial relationship between satellite cells and capillaries, denervation and myofibre grouping. Compared with young muscle, aged muscle contained 53% more type I myofibres, in addition to smaller (-32%) and misshapen (3%) type II myofibres (P<0.05). Aged muscle manifested fewer capillaries (-29%) and satellite cells (-38%) surrounding type II myofibres (P<0.05); however, the spatial relationship between these two remained intact. The proportion of denervated myofibres was ∼2.6-fold higher in old than young muscle (P<0.05). Aged muscle had more grouped type I myofibres (∼18-fold), primarily driven by increased size of existing groups rather than increased group frequency (P<0.05). Aged muscle displayed selective deterioration of type II myofibres alongside increased denervation and myofibre grouping. These data are key to understanding the cellular basis of age-related muscle decline and reveal a pressing need to fine-tune strategies to preserve type II myofibres and innervation status in ageing populations.

A systematic review of health outcomes of public transport use by older adults

Abstract Background and Aim Public transport use has been linked to several health benefits in the general population, and is crucial for older adults’ mobility, due to an age-related decline in mobility, and particularly the ability to use other transport modes. The objective of this systematic review is to determine what is known about the physical and mental health outcomes of public transport use by older adults and to identify remaining gaps in the literature. Methods Five electronic databases were searched in April 2023, with an update in January 2024: Pubmed, Scopus, Web of Science, Ageline and Transport Research International Documentation (TRID). Included were studies that were in English, contained a measure of public transport use as exposure, and any health outcome, including mental or physical health, physical or cognitive function, morbidity, or mortality, among people aged ≥ 60 years. Results Of a total of 2247 unique records that were screened, the full text of 20 was assessed for eligibility and 11 were identified as eligible. Citation search identified two additional studies, amounting to a total of 13 included studies. Significant health outcomes described in assessed studies were decreased obesity and depressive symptoms, and to a lesser extent increased gait speed and cognitive function. Conclusions Initial evidence suggests a positive impact of public transport use on obesity, depressive symptoms, gait and cognitive function, although available research was limited in context and methodology. Further research should focus on determining causality between public transport use and health, and be conducted in more diverse contexts. Transport and urban planners, as well as policymakers, should consider the implications of public transport on the health and independence of older adults. Key messages • Public transport use is linked to reduced obesity and depression among older adults. Links with other health outcomes were reported in several studies, but evidence is scarce. • Current research is limited in terms of quantity, scope, and design. Future research should be conducted in wider contexts, encompass a broader range of health outcomes, and address reverse causality.

The NAD+ precursor nicotinamide riboside protects against postovulatory aging in vitro.

Postovulatory aging (POA) of oocytes is clinically significant as it mirrors the degeneration observed in maternally aged oocytes, leading to substantial impairments in oocyte quality and the success rates of artificial reproductive technology (ART). The molecular alterations associated with POA, such as the degeneration of the first polar body, an increase in perivitelline space, reactive oxygen species (ROS) accumulation, energy depletion, and chromosomal and DNA damage, underscore the urgency of finding interventions to mitigate these effects. This study aims to identify whether nicotinamide riboside (NR) can prevent POA during the process of in vitro culture and raise the success rates of ART. Taking advantage of an in vitro postovulatory oocyte aging model, we examined the morphological integrity and NAD+ levels of ovulated mouse MII oocytes after 24h of culturing. Following in vitro fertilization, we assessed the embryonic developmental potential of oocytes affected by POA. Using immunofluorescence and confocal microscopy, we measured the levels of ROS, mitochondrial function, and γH2AX. We also evaluated spindle assembly and chromosome alignment. Additionally, we detected the distribution of cortical granules to assess the metabolic and quality changes in POA oocytes with the supplementation of NR. To further our analysis, quantitative real-time PCR was conducted to measure the mRNA expression levels of antioxidant enzymes Sod1 and Gpx1 in the oocytes. With 200μM NR supplementation during in vitro culture for 24h, the oocytes from POA demonstrated reduced signs of aging-related decline in oocyte quality, including reduced ROS accumulation, improved mitochondrial function, and corrected mis-localization of cortical granules. This improvement in oocyte quality is likely due to the inhibition of oxidative stress via the NAD+/SIRT1 signaling pathway, which also helped to restore normal spindle assembly and chromosome alignment, as well as reduce the elevated levels of γH2AX, thereby potentially enhancing the embryonic development potential. Current research provides evidence that NR is an efficient and safe natural component that prevents the process of POA and is thus a potential ideal antiaging drug for raising the success rates of ART in clinical practice.

Different risk and protective factors predict change of planning ability in middle versus older age

Age-related cognitive decline has become an increasingly relevant public health issue. However, risk and protective factors of cognitive decline have yet to be investigated prospectively taking into account genetic, lifestyle, physical and mental health factors. Population-based data from middle-aged (40 to 59 years; N = 2,764) and older individuals (60 to 80 years; N = 1,254) were drawn from a prospective community cohort study using the Tower of London (TOL) planning task. Assessments were repeated at a 5-year interval to investigate age-related changes in planning performance and to determine the impact of risk and protective factors. Planning performance improved in middle-aged, but declined in older participants over 5 years. SNPs affecting the dopamine system (COMT, DRD2) and APOE polymorphisms differentially predicted cognitive performance in older vs. middle-aged individuals. For older individuals, high alcohol consumption, antidepressant medication and living without a partner had additional negative predictive power on cognition. In contrast, undiagnosed hypertension, no obstructive lung disease, and fewer years of education predicted cognitive decline in the middle-aged group. The results inform screening for individuals particularly vulnerable to cognitive decline and interventions (e.g., focusing on lifestyle factors) to help maintain cognitive performance into old age.

Reduction in the olfactory ability in aging Mitf mutant mice without evidence of neurodegeneration

Age-related decline occurs in most brain structures and sensory systems. An illustrative case is olfaction. The olfactory bulb (OB) undergoes deterioration with age, resulting in reduced olfactory ability. A decline in olfaction is also associated with early symptoms of neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the underlying reasons are unclear. The microphthalmia-associated transcription factor (MITF) is expressed in the projection neurons (PNs) of the OB–the mitral and tufted (M/T) cells. Primary M/T cells from Mitf mutant mice show hyperactivity, potentially attributed to the reduced expression of a key potassium channel subunit, Kcnd3/Kv4.3. This influences intrinsic plasticity, an essential mechanism involving the non-synaptic regulation of neuronal activity. As neuronal hyperactivity often precedes neurodegenerative conditions, the current study aimed to determine whether the absence of Mitf causes degenerative effects during aging. Aged Mitf mutant mice showed reduced olfactory ability without inflammation. However, an increase in the expression of potassium channel subunit genes in the OBs of aged Mitfmi-vga9/mi-vga9 mice suggests that during aging, compensatory mechanisms lead to stabilization.

Dendritic spines of layer 5 pyramidal neurons of the aging somatosensory cortex exhibit reduced volumetric remodeling.

Impairments in synaptic dynamics and stability are observed both in neurodegenerative disorders and in the healthy aging cortex, which exhibits elevated dendritic spine turnover and decreased long-term stability of excitatory connections at baseline, as well as an altered response to plasticity induction. In addition to the discrete gain and loss of synapses, spines also change in size and strength both during learning and in the absence of neural activity, and synaptic volume has been associated with stability and incorporation into memory traces. Furthermore, intrinsic dynamics, an apparently stochastic component of spine volume changes, may serve as a homeostatic mechanism to prevent stabilization of superfluous connections. However, the effects of age on modulation of synaptic weights remain unknown. Using two-photon excitation (2PE) microscopy of spines during chemical plasticity induction in vitro and analyzing longitudinal in vivo 2PE images after a plasticity-inducing manipulation, we characterize the effects of age on volumetric changes of spines of the apical tuft of layer 5 pyramidal neurons of mouse primary somatosensory cortex. Aged mice exhibit decreased volumetric volatility and delayed rearrangement of synaptic weights of persistent connections, as well as greater susceptibility to spine shrinkage in response to chemical long-term depression. These results suggest a deficit in the aging brain's ability to fine-tune synaptic weights to properly incorporate and retain novel memories. This research provides the first evidence of alterations in spine volumetric dynamics in healthy aging and may support a model of impaired processing and learning in the aged somatosensory system.Significance Statement Aging is known to impact cognitive functions and sensory processing, yet the underlying mechanisms at the synaptic level remain unclear. This study investigates dendritic spine dynamics of layer 5 pyramidal neurons in the aging somatosensory cortex. By employing two-photon excitation microscopy and analyzing spine volume changes during plasticity induction, we reveal that aged mice exhibit decreased volumetric volatility and delayed synaptic weight rearrangement. These alterations may impair the brain's ability to fine-tune synaptic weights, which is crucial for incorporating and retaining new memories. This research provides the first evidence of altered spine volumetric dynamics in healthy aging, suggesting a potential mechanism for impaired processing and learning in the aged cortex. Understanding these changes could aid in mitigation of age-related cognitive decline.

Transplantation of human umbilical cord-derived mesenchymal stem cells improves age-related ovarian functional decline via regulating the local renin–angiotensin system on inflammation and oxidative stress

BackgroundAge-related reproductive aging is a natural and irreversible physiological process, and delaying childbearing is increasingly common all over the world. Transplantation of mesenchymal stem cells (MSCs) is considered a new and effective therapy to restore ovarian function, but the relevant mechanisms remain unclear. Recently, it has been found that there is a local Renin–angiotensin system (RAS) in human ovary and it plays a key role.MethodsAfter collecting follicular fluid from women who received oocyte retrieval for pure male factor infertility, the level of RAS components in it were detected, and the correlation analysis by linear regression. Then, the in vivo experiments on female C57BL/6 mice were designed to measure ovarian function, and the transcription and translation levels of RAS pathway were detected by molecular biology methods. Moreover, the role of RAS in regulating inflammation and oxidative stress in the co-culture system were explored in in vitro experiments on KGN cells.ResultsFirst, a total of 139 samples of analyzable follicular fluid were obtained. The local RAS of ovary, which is independent of systemic RAS (P > 0.05), is affected by age (Pearson r < 0, P < 0.05) and related to ovarian function, inflammation, oxidative stress indexes and assisted reproduction laboratory outcomes (P < 0.05). Next, the ovary/body weight of aging mice decreased significantly and serum sex hormones levels changed significantly (P < 0.01). The number of functional follicles decreased, while the atresia follicles increased (P < 0.05). After MSCs transplantation, all the above measures have been partially recovered (P < 0.05). Although several RAS components in aging ovary changed, MSCs only improved the expression level of AT1R (P < 0.05). Furthermore, the secretion ability and mitochondrial membrane potential of aging KGN cells decreased, while the intracellular ROS level and the aging cells ratio increased (P < 0.01). All the above measures have been partially recovered when co-cultured with MSCs (P < 0.05). After Ang(1–7) were added into the co-culture system, the above have been more significantly restored compared with Ang II (P < 0.05). Nevertheless, there was no statistical difference in estradiol level no matter which one was added (P > 0.05).ConclusionsTogether, our findings indicate that a novel possible mechanism to explain how stem cells restore age-related ovarian functional decline.

Computationally Driven Discovery and Characterization of SIRT3-Activating Compounds that Fully Recover Catalytic Activity under NAD+ Depletion

Many chronic, age-related disorders could be mitigated by enhancing the activity of enzymes that regulate biochemical signaling pathways, but all known modes of enzyme activation rely on allosteric binding sites, which have only been identified in less than 10% of proteins. Sirtuins (SIRT1-7) are nicotinamide adenine dinucleotide (NAD+)-dependent deacylases playing critical roles in lifespan and age-related diseases. The physiological importance of sirtuins and the reduction in their catalytic activity with the age-related decline in NAD+ levels have stimulated intense interest in designing sirtuin-activating compounds; however, except for substrate-specific allosteric SIRT1 activators, methodologies for rational design of sirtuin-activating compounds are lacking. Here, we introduce methods for the activation of such enzymes that do not rely on allosteric binding sites, and we demonstrate their successful application to the discovery of first-in-class activators of sirtuin enzymes. We establish how all-atom simulations of an enzyme’s active site under the potential of a small molecule modulator can be used to identify molecular properties that achieve desired changes in local enzyme conformational degrees of freedom conducive to the enhancement of catalytic activity. We apply computational high-throughput screening based on this biophysical model for activation of sirtuin enzymes to the major mitochondrial sirtuin SIRT3, which plays a critical role in age-related disorders but does not have a known allosteric site; we thereby identify first-in-class, nonallosteric activators of this enzyme. These compounds are the first reported steady-state activators of the major mitochondrial sirtuin enzyme, and they operate according to a mode of action not shared by any existing drug. Two such compounds can almost double the catalytic efficiency of SIRT3 with respect to NAD+, thus compensating for the loss in SIRT3 activity that occurs due to the age-related decline in NAD+, and they may be developed for therapeutic applications to combat multiple types of age-related disorders. These discoveries establish a foundation for the development of a new class of drugs that function through the activation of enzymes by modulation of local conformational ensembles. Published by the American Physical Society 2024

A review of artificial intelligence-based brain age estimation and its applications for related diseases.

The study of brain age has emerged over the past decade, aiming to estimate a person's age based on brain imaging scans. Ideally, predicted brain age should match chronological age in healthy individuals. However, brain structure and function change in the presence of brain-related diseases. Consequently, brain age also changes in affected individuals, making the brain age gap (BAG)-the difference between brain age and chronological age-a potential biomarker for brain health, early screening, and identifying age-related cognitive decline and disorders. With the recent successes of artificial intelligence in healthcare, it is essential to track the latest advancements and highlight promising directions. This review paper presents recent machine learning techniques used in brain age estimation (BAE) studies. Typically, BAE models involve developing a machine learning regression model to capture age-related variations in brain structure from imaging scans of healthy individuals and automatically predict brain age for new subjects. The process also involves estimating BAG as a measure of brain health. While we discuss recent clinical applications of BAE methods, we also review studies of biological age that can be integrated into BAE research. Finally, we point out the current limitations of BAE's studies.

Differential temporal decline of cerebral oxytocin and μ-opioid receptor density during the aging process in mice.

Aging is often associated with changes in social, sexual, emotional and pain functioning, as well as with the increased prevalence of certain psychopathologies. However, the neurodevelopmental basis underpinning these age-related changes remains to be determined. Considering the key roles of oxytocin (OTR) and μ-opioid (MOPr) receptor systems in regulating social, sexual, pain, reward and emotional processing, it seems plausible that they are also implicated in age-related behavioural alterations. Although the ontogeny of both receptors has been well characterized in rodent brains from early development till adulthood, little is known concerning the neuroadaptations occurring from middle age to old age. Therefore, we mapped the neuroadaptations in OTR and MOPr in the brains of mice at those developmental endpoints. Quantitative OTR and MOPr autoradiographic binding was carried out in the brains of male mice at 2, 6, 9, 12 and 18 months of age. A significant whole brain decline in OTR density was detected between 2 and 6months of age, with no additional decline thereafter. Interestingly, for MOPrs, the decline in density was not detected until 9months of age. Region-specific age-related decline in OTR density was concentrated in the lateral anterior olfactory nuclei (AOL) and, for MOPr, in the AOL and the nucleus accumbens for MOPr. Identifying the tipping point of these age-related variations in both receptors may assist with our understanding of the neurobiology underlining age-related changes in social, pain and emotional functioning/processing. It may also help us target interventions to specific developmental windows to abrogate certain age-related psychopathologies.

Altered Proteasome Composition in Aging Brains, Genetic Proteasome Augmentation Mitigates Age-Related Cognitive Declines, and Acute Proteasome Agonist Treatment Rescues Age-Related Cognitive Deficits in Mice.

The aging brain experiences a significant decline in proteasome function, The proteasome is critical for many key neuronal functions including neuronal plasticity, and memory formation/retention. Treatment with proteasome inhibitors impairs these processes. Our study reveals a marked reduction in 20S and 26S proteasome activities in aged mice brains driven by reduced functionality of aged proteasome. This is matched by a decline in 20S proteasome but an increase in 26S proteasome. Our data suggests this may be a compensatory response to reduced functionality. By overexpressing the proteasome subunit PSMB5 in the neurons of mice, enhancing proteasome function, we slowed age-related declines in spatial learning and memory as well neuromuscular declines. We then showed acute treatment with a proteasome activator to rescue spatial learning and memory deficits in aged mice. These findings highlight the potential of proteasome augmentation as a therapeutic strategy to mitigate age-related cognitive declines.

Aging affects the mouse brain in a region-specific manner.

Aging-related cognitive decline is emerging as a health concern during the aging process of the global population. Hahn and colleagues found that glial aging was particularly accelerated in white matter compared to cortical regions. Specialized neuronal populations showed region-specific changes in gene expression. Acute dietary restriction triggers a reprogramming of genes associated with the circadian clock in glial cells, whereas injections of young mouse plasma selectively reverse age-related expression patterns. The discovery of region-specific aging could enhance our understanding of the aging process and offer new possibilities for innovative treatment strategies and interventions for cognitive impairments related to aging.

Hearing loss and its relation to longitudinal changes in white matter microstructure in older adults: The Rotterdam Study

Hearing loss is considered a potentially modifiable risk factor for dementia. The sensory deprivation theory postulates that hearing loss adversely affects cognition in older adults through structural brain changes, but longitudinal studies are scarce. To find evidence for a possible detrimental effect of hearing loss on white matter microstructure, we carried out a longitudinal study in the population-based Rotterdam Study. A total of 1877 participants with a median age at baseline of 56.4 years (IQR: [52.2–60.0]) underwent audiometry and had longitudinal diffusion imaging data available with a mean follow-up of 4.0 years. A lower level of hearing acuity was associated with worse white matter microstructure in the left uncinate fasciculus and superior longitudinal fasciculus at baseline. Poorer hearing acuity was also associated with faster microstructural deterioration over time in the left superior longitudinal fasciculus. The strongest effects were observed for low-frequency hearing thresholds, while the high-frequency thresholds showed the weakest associations. These results suggest that hearing loss may contribute to the age-related decline in brain structure, consistent with the sensory deprivation theory.

Epigenetic and 3D genome reprogramming during the aging of human hippocampus.

Age-related cognitive decline is associated with altered physiology of the hippocampus. While changes in gene expression have been observed in aging brain, the regulatory mechanisms underlying these changes remain underexplored. We generated single-nucleus gene expression, chromatin accessibility, DNA methylation, and 3D genome data from 40 human hippocampal tissues spanning adult lifespan. We observed a striking loss of astrocytes, OPC, and endothelial cells during aging, including astrocytes that play a role in regulating synapses. Microglia undergo a dramatic switch from a homeostatic state to a primed inflammatory state through DNA methylome and 3D genome reprogramming. Aged cells experience erosion of their 3D genome architecture. Our study identifies age-associated changes in cell types/states and gene regulatory features that provide insight into cognitive decline during human aging.

Transcranial Direct Current Stimulation for Improving Balance in Healthy Older Adults and Older Adults with Stroke: A Scoping Review.

Background/Objectives: Age-related decline in balance and postural control is common in healthy elders and is escalated in aging adults with stroke. Transcranial direct current stimulation (tDCS) has emerged as one of the promising brain stimulations adjoining therapeutic exercise to enhance the recovery of balance and motor functions in persons with and without neurological disorders. This review aims to summarize and compare the available evidence of the tDCS on improving balance in the older adults without neurological disorders and the older adults with stroke. Methods: The Ovid (Medline) database was searched from its inception through to 06/15/2024 for randomized controlled trials investigating tDCS for improving balance in older adults with and without stroke. Results: Overall, 20 appropriate studies (including 271 stroke subjects and 259 healthy older adults) were found. The data indicate mixed results of tDCS for improving balance in older adults with and without stroke. Conclusions: Based on current research evidence, we have not found a specific tDCS protocol that is more effective than other tDCS protocols for improving balance and postural control in healthy older adults and older adults with stroke. Further research should explore the ideal tDCS approach, possibly in conjunction with standard interventions, to optimize postural control and balance in healthy older adults and older adults with stroke.

Retirement through rose-colored glasses: greater positivity bias in retired relative to working older adults

Abstract Retirement has been associated with declines in memory beyond typical age-related memory decline. This may impact the ability to remember distinct events, as older adults (OA) are susceptible to interference in memory across experiences with overlapping features. Impaired hippocampal pattern separation, a computation that allows for the disambiguation of similar experiences as unique events, is thought to underlie age-related impairment in memory. Furthermore, positive experiences tend to be better remembered than neutral or negative experiences in aging. Socioemotional selectivity theory suggests that awareness of a limited remaining lifespan leads OA to prioritize emotionally fulfilling experiences, often leading to a bias towards positive information compared to negative or neutral information. However, the potential role of retirement in contributing to these age-related changes in memory has yet to be examined. Memory measures that tax hippocampal pattern separation may be more sensitive to memory impairment in retirement compared to standard memory measures. Retirement may exacerbate awareness of reduced remaining time, such that retired OA may experience a greater positivity bias in memory than their working peers. Here, we utilized an emotional memory task that taxes hippocampal pattern separation to examine memory in age-matched retired and working OA. We found that retired OA show selective impairments for memories with high interference and a greater positivity bias in memory compared to their working peers. These findings suggest that retirement may accelerate age-related memory changes, including greater susceptibility to interference as well as a bias toward remembering positive relative to neutral information.