Aging & Longevity

Navigating uneven terrain poses a significant challenge for older adults, often resulting in falls. Identifying the neural correlates of walking on uneven terrain might help understand the mechanisms of age-related mobility decline. We examined age and physical function group differences in white matter microstructure and tested whether associations between white matter measures and uneven-terrain walking behavior differed between these groups. Twenty-two young adults (22.45 ± 2.58 years) and 86...

Whether reversal of biological age and/or aging is possible is among the most actively debated topics in the field of aging. Here, we consider the meaning of biological age reversal and its burden of proof, focusing on foundational issues and the language we use to debate these questions.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose pathological course involves amyloid-β (Aβ) deposition, tau abnormalities, neuroinflammation, and neurovascular dysfunction. Interest in the microbiota-gut-brain axis does not arise because gut dysbiosis has been established as an independent initiating cause of sporadic AD, but because this axis connects modifiable peripheral factors-including diet, medication, ageing, and intestinal physiology-with barrier homeostasis,...

Ageing research has undergone a paradigm shift from descriptive theories to a mechanistic understanding grounded in the interconnected biological processes. This work synthesizes the current landscape of ageing research, emphasizing the critical role of biomarkers in translating mechanistic insights into clinical application. Biomarkers, ranging from molecular and cellular markers to functional and imaging parameters, serve as essential tools for quantifying biological age, assessing the...

Sarcopenia has consensus criteria on three continents and an all-cause mortality hazard ratio near 1.6, yet no drug is approved for the primary age-related condition and agents that reliably enlarge muscle have not improved the strength and gait-speed endpoints that define it. We approach this translational failure from the biology rather than the pipeline. Ageing degrades four properties of skeletal muscle that jointly determine force production and are each druggable in principle: innervation,...

Although motor and cognitive functions are closely interconnected in daily life, they are typically assessed separately in fall assessments. This dual-center cross-sectional, observational study examined the discriminative performance of agility and motor-cognitive assessments to distinguish between community-dwelling older adults with and without a history of falls, compared with established motor and cognitive tests. A total of 231 participants (103 with a history of falls; age 71.9 ± 7.5...

Mitochondria are continuously exposed to damage that contributes to aging and disease. While prolongedly damaged mitochondria are eliminated by mitophagy, how cells respond to transient damage remains unclear. Here, we establish a cell-based system to induce transient mitochondrial stress and resolve its recovery dynamics. We identify the E3 ubiquitin ligase mahogunin ring finger 1 (MGRN1) as a damage-threshold sensor that discriminates between transient and prolonged mitochondrial insults....

Organ structure, including the organization of cells, vasculature and extracellular matrix, underpins its function, yet how structure changes with age remains mostly unknown. Here we developed PathStAR, a framework that quantifies tissue structural aging from routine histopathology images, without being trained to predict chronological age. Applying PathStAR to 25,306 post-mortem biopsies from 40 tissues in 970 donors aged 21-70 years revealed that organ structural aging progresses via distinct,...

Pulmonary hypertension (PH) frequently complicates heart failure with reduced ejection fraction (HFrEF), worsening prognosis despite limited therapeutic options. Whether sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve PH beyond their established hemodynamic effects remains unclear. Seventy-four patients with ischemic HFrEF after acute myocardial infarction and a high echocardiographic probability of PH were prospectively enrolled in a single-center, non-randomized study. Patients...

No abstract

Ageing is an independent, non-modifiable risk factor for myocardial infarction (MI). It is also characterized by chronic, low-grade inflammation (inflammaging) and progressive cardiovascular senescence. These ageing-associated processes alter cytokine networks and innate and adaptive immune-cell function, promote endothelial dysfunction, and compromise post-infarction repair, thereby increasing myocardial susceptibility to ischaemia and adverse cardiac remodelling in the elderly. Lifestyle...

Mesenchymal stem cells (MSCs) maintain bone homeostasis through osteogenic differentiation. During aging, MSCs undergo a fate shift toward adipogenesis rather than osteogenesis, but the post-transcriptional mechanisms remain unclear. Here, we identify ovarian tumor domain-containing protein 1 (OTUD1) as an RNA-binding protein that controls MSC fate by stabilizing osteogenic transcripts. OTUD1 directly binds and stabilizes BMP2 mRNA, thereby supporting osteogenic differentiation. In vivo, OTUD1...

We develop an integrated, high-throughput platform to evaluate pharmacological lifespan-extending interventions across five model organisms spanning unicellular to mammalian biology including yeast, nematodes, fruit flies, killifish, and mice. By combining automated imaging, miniaturized assays, and deep-learning-based death detection, we evaluate over 400 compounds across thousands of conditions. In S. cerevisiae, a miniaturized PI/flow cytometry CLS assay enables scalable screening and...

Black carbon (BC) from biomass burning is a key component of the global carbon cycle, and radiocarbon (^(14)C) age of riverine BC is commonly used to constrain its terrestrial residence time. However, whether ^(14)C-free BC from fossil sources significantly contributes to riverine BC and biases these ages remains unclear. Here, we track dissolved and particulate BC (DBC, PBC) along a river continuum from forested headwaters to an urbanized estuary. This urbanization gradient allows us to...

Long-term exposure to ultraviolet (UV) radiation can cause sunburn, skin aging, and skin cancers. Conventional sunscreens typically combine organic UV filters and inorganic particles for photoprotection, yet concerns remain regarding skin penetration, systemic effects, and reactive oxygen species generation. Inspired by natural photoprotective mechanisms in plants, we develop a series of all-small-molecule sunscreen hydrogels based on natural polyphenols through a facile one-pot assembly...

Annual killifishes of the genus Nothobranchius compress a vertebrate life cycle into a few months, which is what makes them useful in aging research, yet no broad biochemical description of ageing exists for N. guentheri. In a cross-sectional design, we measured 27 clinical chemistry analytes in whole-body homogenates of male and female fish sampled at 3, 6 and 9 months of age (20 analytical samples). Age trends were assessed by Spearman rank correlation, and age, sex and their interaction by...

SIRT1, a sirtuin family member, has been extensively documented to be closely linked to aging and aging-related disease. Cellular senescence is a state of irreversible cell cycle arrest that functions as a key driver of aging. During cellular senescence, LINE-1 (L1) retrotransposable elements become transcriptionally activated and stimulate a type-I interferon (IFN-I) response. L1 activity has been strongly linked to aging and a variety of age-related disorders. However, whether SIRT1 influences...

Several dietary patterns have been associated with better health outcomes. However, the extent to which adherence to different so-called healthy diets overlaps, whether these dietary patterns are equally beneficial, and whether they are associated with similar DNA methylation profiles, remains unclear. Therefore, we investigate the overlap in adherence to ten diet quality scores, and examine the associations of these scores with both biological aging markers and DNA methylation profiles. We use...

Non-communicable diseases (NCDs) dominate global mortality yet remain pervasive despite extensive prevention efforts, suggesting current explanatory frameworks may be incomplete. We propose the "Adaptive Cost Hypothesis": many NCDs represent not primarily lifestyle-mismatch diseases but rather inevitable trade-offs inherent in adaptive epigenetic programming optimized for reproductive success within ancestral human lifespans of 40-60 years. Early-life adversity calibrates immune, metabolic, and...

Transcranial direct current stimulation (tDCS) targeting the primary motor cortex (M1) has previously been shown to enhance motor learning in older adults. However, findings across studies are inconsistent, which may be partly due to variability in stimulation parameters and montages across experimental protocols. We aimed to replicate the effect of 1 mA conventional anodal tDCS over the M1 hotspot during one session of motor sequence learning on retention (24 h) compared to sham stimulation in...