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Understanding how secreted factors from aged tissue, often referred to as the senescence-associated secretome, reshape cellular phenotypes remains a major challenge due to the complexity of downstream molecular cascades. Here, we present a computational framework for in silico perturbation modeling designed to predict distinct transcriptional responses to age-specific extracellular environmental cues. We exemplify applications of this framework using articular chondrocytes exposed to secretomes...

Aging is a complex biological phenomenon. Because health can vary greatly even among persons of the same chronological age, biological age, an integrative measure of physiological and molecular deterioration, may be a more useful construct for promoting longevity. Biological aging does not represent a "fixed" process; rather, it can be reversible. Many markers of biological aging exist. Epigenetic clocks use patterns of aging-related DNA methylation to predict morbidity and mortality, but other...

The progressive decline of skeletal muscle (SkM) regeneration is a central feature of ageing. In sarcopenia, the age-related loss of muscle mass and function is driven by exhaustion and dysfunction of resident muscle stem cells and by degenerative remodeling of their regenerative niche, including cellular senescence, chronic inflammation, and fibro-adipogenic conversion. Accordingly, cell-based therapies aim to reverse this regenerative failure through direct myofiber replacement, paracrine...

Age-related skeletal muscle decline contributes substantially to loss of physical independence and impaired metabolic health, yet its trajectory varies considerably among individuals. Fundamental determinants of muscle function, including architecture, cellular composition, and metabolic capacity, are established during prenatal and early postnatal development. During these windows, skeletal muscle exhibits substantial plasticity in response to parental physiological and metabolic states,...

CONCLUSIONS: Post-glucose FGF21 response is associated with lower habitual sucrose intake in older adults, but this association is attenuated among individuals with GDS. These observations may inform integrated endocrine and psychological approaches to mitigating nutritional imbalance in late-life depression.

Ageing is associated with impairments in muscle force-generating capacity and tendon mechanical properties, yet its effects on stretch-shortening cycle (SSC) function remain unclear. We combined in vivo ultrasonography with dynamometric and kinematic measurements to investigate the muscle-tendon mechanisms underpinning SSC performance in older adults. Fourteen young (28 ± 5 years) and fifteen older adults (67 ± 3 years) performed electrically evoked plantarflexion contractions on an isokinetic...

The extracellular matrix (ECM) undergoes extensive alterations during aging, yet its contribution to organismal aging remains partially understood. Emerging evidence now identifies elastin-derived fragments as bioactive matrikines that function as systemic drivers of inflammaging and aging, rather than passive byproducts of tissue degradation. This Viewpoint examines recent findings on elastin-derived fragments in the context of matrikine biology and aging, highlighting their emerging roles as...

This systematic review investigates the mediating factors in the relationship between ambient air pollution exposure and cognitive aging. We identified 16 studies examining 72 unique exposure-mediator-outcome associations for six pollutants (PM2.5, PM10, NO2, NOX, black carbon, and PM1 components). The most studied pollutant was PM2.5 (65% of analyses). Cognitive outcomes included memory, cognitive processing speed, and clinically diagnosed conditions such as dementia incidence. Potential...

With the ageing of the global population, age-related cardiovascular diseases have become a significant burden on global public health. Traditional Chinese Medicine (TCM) possesses a deep theoretical foundation and extensive clinical experience in delaying age-related vascular diseases. However, a systematic synthesis of modern scientific evidence in this field remains lacking. This article provides a systematic review of research progress on the molecular mechanisms of TCM interventions in...

Physical exercise is a potent modifier of CNS aging, but its relationship with the cyclin-dependent kinase inhibitor p21 (CDKN1A) is neither uniformly suppressive nor equivalent to cellular senescence. Direct evidence remains sparse and preclinical. Sustained physiological exercise reduced hippocampal or cortical p21-associated signatures in models of metabolic distress, natural aging, and amyloid pathology. Conversely, acute treadmill exercise transiently increased hippocampal Cdkn1a, while...

Pancreatic cancer patients with at least 21 natural teeth survived nearly two years longer after surgery than those with fewer teeth in a study of 339 people. Researchers suspect tooth loss may reflect decades of inflammation, frailty, nutrition, and other factors tied to the body’s overall resilience.

Scientists have linked a specific gut bacterium, Roseburia inulinivorans, to stronger muscles in both humans and mice. Older adults who carried it had 29% greater handgrip strength, while treated mice gained about 30% more grip strength and developed larger, more fast-twitch muscle fibers. The bacterium was also less common in older people. Researchers say it could eventually become a probiotic candidate for helping combat age-related muscle loss.

A few minutes of sprinting may reshape the bloodstream far more dramatically than a much longer moderate workout. Six 30-second sprints altered nearly a quarter of the blood proteins measured and more than 200 metabolites, while 90 minutes of moderate cycling produced far smaller immediate changes. Many of the proteins affected by sprinting were also associated with lower risks of obesity, type 2 diabetes, and other metabolic diseases.

A hormone already known for curbing appetite and supporting weight loss may have a surprising second job: protecting the liver from inflammation and scarring. Researchers at McMaster University found that GDF15 activates a previously unknown brain-to-liver pathway that triggers the release of glucocorticoids, helping calm immune activity in the liver.

AI may be able to predict how strongly someone will respond to a vaccine before they receive it. By analyzing antibody patterns in more than 4,000 people, researchers found signs of “immune readiness” that helped distinguish strong responders from weak ones. Surprisingly, even some healthy people responded poorly, while some immunosuppressed people mounted strong responses.

Immunosenescence is not a uniform decline but a trajectory shaped jointly by age and sex. Using continuous high-dimensional immunophenotyping, we show that aging T cells accumulate a senescent signature of CD28 loss and CD57 gain, and that males reach an inverted CD4:CD8 ratio earlier and more severely than females. We argue that age-by-sex stratification should guide vaccination and geroprotective strategies in an aging population.

Aging biomarkers can potentially allow researchers to rapidly monitor the impact of an aging intervention without the need for decade-spanning trials. However, before the use of aging biomarkers, such as epigenetic clocks, as surrogate endpoints, their responsiveness to interventions that target aging must be tested. Here we curate TranslAGE, a harmonized database of 51 public and private longitudinal interventional studies, and calculate a consistent set of 16 prominent epigenetic clocks for...

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Frailty and cognitive impairments frequently co-occur in older adults. It remains unclear whether this overlap reflects shared underlying biological mechanisms or parallel but distinct disease pathways. We hypothesize that physical weakness and cognitive impairment share circulating markers already in an early disease stage. We therefore recruited and analyzed a relatively healthy population with partially overlapping pre-frailty and mild cognitive impairment (MCI), and applied a multi-omics...