Aging & Longevity

With advancements in veterinary care and the growing recognition of pets as integral member of the family, the lifespans of dogs and cats have significantly increased, leading to a higher prevalence of age-related conditions, including cognitive dysfunction syndrome (CDS). CDS adversely impacts pets' quality of life and presents emotional and practical challenges for owners. Given its similarities to Alzheimer's disease in humans, CDS has gained attention as a target for nutrition-based...

Photobiomodulation (PBM) therapy, a non-thermal light therapy using nonionizing light sources, has shown therapeutic potential across diverse biological processes, including aging and age-associated diseases. In 2023, scientists from the National Institute on Aging (NIA) Intramural and Extramural programs convened a workshop on the topic of PBM to discuss various proposed mechanisms of PBM action, including the stimulation of mitochondrial cytochrome C oxidase, modulation of cell membrane...

Cells are subjected to dynamic mechanical environments which impart forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and the SASP is not well understood. Here, we show that mechanical tension, modeled using cell culture substrate...

If a shortened lifespan is evolutionarily advantageous, it becomes more likely that nature will strive to change it accordingly, affecting how we understand aging. Premature mortality because of aging would seem detrimental to the individual, but under what circumstances can it be of value? Based on a relative incremental increase in fitness, simulations were performed to reveal the benefit of death. This modification allows for continuous evolution in the model and establishes an optimal...

In Huntington's disease (HD), striatal projection neurons (SPNs) degenerate during midlife; the core biological question involves how the disease-causing DNA repeat (CAG)(n) in the huntingtin (HTT) gene leads to neurodegeneration after decades of biological latency. We developed a single-cell method for measuring this repeat's length alongside genome-wide RNA expression. We found that the HTT CAG repeat expands somatically from 40-45 to 100-500+ CAGs in SPNs. Somatic expansion from 40 to 150...

CONCLUSIONS: In persons with CSS, NfL and the Aβ(40)/Aβ(42)-ratio were related to mortality and incident stroke, respectively, whereas associations of GFAP with adverse outcomes varied by ApoE genotype. These biomarkers might play a role in linking aging, cardiovascular and neurodegenerative diseases.

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Pubertal timing is highly variable and is associated with long-term health outcomes. Phenotypes associated with pubertal timing include age at menarche, age at voice break, age at first facial hair and growth spurt, and pubertal timing seems to have a shared genetic architecture between the sexes. However, puberty phenotypes have primarily been assessed separately, failing to account for shared genetics, which limits the reliability of the purported health implications. Here, we model the common...

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Sarcopenia, the pathological age-related loss of muscle mass and strength, contributes to physical decline, frailty, and diminished healthspan. The impact of sarcopenia is expected to rise as the aging population grows, and treatments remain limited. Therefore, novel approaches for enhancing physical function and strength in older adults are desperately needed. Recent evidence suggests that deficits in motor neuron excitability contribute significantly to age-related weakness. Accordingly, we...

Ageing is the primary driver of age-associated chronic diseases and conditions. Asian populations have traditionally been underrepresented in studies understanding age-related diseases. Thus, the Ageing BIOmarker Study in Singaporeans (ABIOS) aims to characterise biomarkers of ageing in Singaporeans, exploring associations between molecular, physiological, and digital biomarkers of ageing. This is a single-centre, cross-sectional study that recruits healthy community-dwelling adults (≥ 21 years)...

Biological age estimation from DNA methylation and determination of relevant biomarkers is an active research problem which has predominantly been tackled with black-box penalized regression. Machine learning is used to select a small subset of features from hundreds of thousands of CpG probes and to increase generalizability typically lacking with ordinary least-squares regression. Here, we show that such feature selection lacks biological interpretability and relevance in the clocks of the...

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CONCLUSIONS: Physical activity could reduce the risk of all-cause/cardiovascular mortality and was mediated by vitamin D in older Chinese adults.

Colorectal cancer (CRC) constitutes the second leading cause of cancer-related death worldwide and advanced CRCs are resistant to targeted therapies, chemotherapies and immunotherapies. p38α (Mapk14) has been suggested as a therapeutic target in CRC; however, available p38α inhibitors only allow for insufficient target inhibition. Here we describe a unique class of p38α inhibitors with ultralong target residence times (designated ULTR-p38i) that robustly inhibit p38α downstream signaling and...

Myelin loss induces neural dysfunction and contributes to the pathophysiology of neurodegenerative diseases, injury conditions, and aging. Because remyelination is often incomplete, better understanding endogenous remyelination and developing remyelination therapies that restore neural function are clinical imperatives. Here, we use in vivo two-photon microscopy and electrophysiology to study the dynamics of endogenous and therapeutic-induced cortical remyelination and functional recovery after...

Fracture is an under-recognized but common complication of diabetes mellitus, with an incidence approaching twofold in type 2 diabetes mellitus (T2DM) and up to sevenfold in type 1 diabetes mellitus (T1DM) compared with that in the general population. Both T1DM and T2DM induce chronic hyperglycaemia, leading to the accumulation of advanced glycosylation end products that affect osteoblast function, increased collagen crosslinking and a senescence phenotype promoting inflammation. Together with...

Female individuals who are post-menopausal present with higher incidence of knee osteoarthritis (KOA) than male counterparts; however, the mechanisms underlying this disparity are unknown. The most commonly used preclinical models lack human-relevant menopausal phenotypes, which may contribute to our incomplete understanding of sex-specific differences in KOA pathogenesis. Here we chemically induced menopause in middle-aged (14-16 months) C57/BL6N female mice. When we mapped the trajectory of...

D-β-hydroxybutyrate, BHB, has been previously proposed as an anti-senescent agent in vitro and in vivo in several tissues including vascular smooth muscle. Moreover, BHB derivatives as ketone esters alleviate heart failure. Here, we provide evidence of the potential therapeutic effect of BHB on Hutchinson-Gilford progeria syndrome (HGPS), a rare condition characterized by premature aging and heart failure, caused by the presence of progerin, the aberrant protein derived from LMNA/C gene c.1824C...