Aging & Longevity

Alzheimer's disease (AD) is the most prevalent form of dementia worldwide. It is a multifaceted condition resulting from interplay of genetic mutations (e.g., APP, PSEN1, PSEN2) that account for less than 5% of cases, several genetic risk variants such as APOE4, TREM2, CD33, CLU, SORL1, and CR1 contribute to disease susceptibility and epigenetic factors, which may mediate the influence of environmental and lifestyle factors over time. Other critical contributors such as aging, protein misfolding...

Aging is associated with increased retinal cell apoptosis, which contributes to decreases in retinal function. Apoptotic retinal cell clearance relies on microglial efferocytosis, but the impact of aging on this process has not been fully elucidated. In this study, we aimed to shed light on this by using single-cell RNA sequencing (sc-RNA-seq) to compare young and aged mouse retinal transcriptional profiles, in which 74,412 retinal cells from young and aged mice were classified into 10...

The aberrant expression of S100A11 has been identified in various malignancies but its functional roles and underlying mechanisms in colorectal cancer (CRC) have not been fully elucidated. Therefore, this study was designed to investigate the expression of S100A11 and its functional significance in CRC, indicating that S100A11 is significantly upregulated and correlates with poor survival outcomes in CRC. Functionally, S100A11 knockdown in CRC cell lines inhibited cell proliferation, invasion,...

Large-scale genomic studies focusing on the genetic contribution to human aging have mostly relied on cross-sectional data. With the release of longitudinally curated aging phenotypes by the UK Biobank (UKBB), it is now possible to study aging over time at genome-wide scale. In this work, we evaluated the suitability of competing models of change in realistic simulation settings, performed genome-wide association scans on simulation-validated measures of age-related deweekcline, and followed up...

Obesity-related osteoarthritis (OA) and the molecular mechanisms governing multiple joint structural changes that occur with obesity are not well understood. This study investigated the progression of obesity in mice and validated the results using human joint samples post-arthroplasty. The results show that obesity is associated with the degeneration of the cartilage layer and abnormal remodeling of the subchondral bone layer, and this occurs alongside aging and DNA damage in chondrocytes,...

CONCLUSIONS: LGBQ women were more likely than straight women to be exposed to breast cancer risk factors, which were compounded by lower screening and facing health care access barriers. It is crucial to identify interventions for screening and risk reduction that are accessible and effective for LGBQ women, particularly bisexual/queer women and those aging into screen-eligibility.

Replicative senescence occurs in response to shortened telomeres and is triggered by ATM and TP53-mediated DNA damage signaling that blocks replication. hTERT lengthens telomeres, which is thought to block damage signaling and the onset of senescence. We find that normal diploid fibroblasts expressing hTERT mutants unable to maintain telomere length do not initiate DNA damage signaling and continue to replicate, despite having telomeres shorter than senescent cells. The TRF1 and TRF2 DNA binding...

Aging-related retinal degeneration and vision loss have been severely affecting the elderly worldwide. Previously, we showed that the m⁶A reader YTHDF2 is a negative regulator for dendrite development and protection of retinal ganglion cells (RGC) in mice. Here, we further show that conditional ablation of Ythdf2 protects the retina from RGC dendrite shrinking and vision loss in aged mice. Additionally, we identify Hspa12a and Islr2 as the potential YTHDF2 target mRNAs mediating these effects....

"Biological aging clocks"-composite molecular markers thought to capture an individual's biological age-have been traditionally developed through bulk-level analyses of mixed cells and tissues. However, recent evidence highlights the importance of gaining single-cell-level insights into the aging process. Microglia are key immune cells in the brain shown to adapt functionally in aging and disease. Recent studies have generated single-cell RNA-sequencing (scRNA-seq) datasets that...

The X-linked histone demethylase, UTX (KDM6A), is a master regulator of gene enhancers, though its role in self-renewing epithelia like the skin is not well understood. Here, we find that UTX is a key regulator of skin differentiation via the regulation of retinoic acid (RA) signaling, an essential metabolic pathway in both skin homeostasis, as well as in the treatment of an array of skin conditions ranging from cancer and acne to aging. Through deletion of Utx in the skin, we demonstrate direct...

Aging is the primary risk factor for Alzheimer's disease (AD), and the aging brain shares many characteristics with the early stages of AD. This study investigates the interplay between aging and amyloid-beta (Aβ) induced pathology. We developed an AD-like in vivo model, using the stereotactic injection of Aβ(1-42) oligomers into the hippocampi of aged mice. Cognitive impairments were assessed using a Y maze. Immunohistochemical and protein analyses were conducted to evaluate neuronal survival,...

DNA damage is a serious threat to cellular viability, and it is implicated as the major cause of normal ageing. Hence, targeting DNA damage therapeutically may counteract age-related cellular dysfunction and disease, such as neurodegenerative conditions and cancer. Identifying novel DNA repair mechanisms therefore reveals new therapeutic interventions for multiple human diseases. In neurons, non-homologous end-joining (NHEJ) is the only mechanism available to repair double-stranded DNA breaks...

To address the challenges of an ageing population, it is important to promote health by identifying factors for healthy ageing. The aim of this study was to investigate the bidirectional association between physical activity (PA) and sleep in healthy Japanese super-seniors over the age of 80. For approximately 1 year, 124 participants wore wearable devices and answered daily lifestyle questionnaires. PA was defined as daily step count and minutes in light activity. Sleep was measured using 24-h...

Pneumococcal vaccination is crucial in preventing Streptococcus pneumoniae infections in older adults. However, vaccine responses often diminish with age. This study investigates serotype-specific IgM and IgG responses in relation to opsonophagocytic activity (OPA) following thirteen-valent pneumococcal conjugate (PCV13) vaccination in younger (26-49 y; n = 44), middle-aged (50-64 y; n = 71), and older adults (65-98 y; n = 141). Both OPA and IgM responses declined with age, while IgG responses...

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide expressed in the nervous system and also in various peripheral tissues, including the musculoskeletal system. PACAP has an important function in the regulation of chondrogenesis and plays a protective role in cartilage oxidative and mechanical stress. PACAP knockout (KO) mice show early signs of aging and osteoarthritis in knee joint articular cartilage. Its specific, most potent receptor is the PAC1 receptor, the...

Neurodegenerative diseases, such as amyotrophic lateral sclerosis, are often associated with mutations in stress granule proteins. Aberrant stress granule condensate formation is associated with disease, making it a potential target for pharmacological intervention. Here, we identified lipoamide, a small molecule that specifically prevents cytoplasmic condensation of stress granule proteins. Thermal proteome profiling showed that lipoamide stabilizes intrinsically disordered domain-containing...

Aging negatively impacts central nervous system function; however, there is limited information about the cellular impact of aging on peripheral nervous system function. Importantly, injury to vulnerable peripheral axons of dorsal root ganglion (DRG) neurons results in somatosensory dysfunction, such as pain, at higher rates in aged individuals. Cellular senescence is common to both aging and injury and contributes to the aged pro-inflammatory environment. We discovered DRG neuron senescence in...

CONCLUSION: The integration of the MPI into multidisciplinary taking care of old patients with hip fractures may provide a structured approach for individualizing treatment decisions, considering aspects such as prognosis, functional autonomy, and cognitive status. Further studies are needed to validate the long-term outcomes of this approach.

As the Pacific Plate migrates over the mantle plume below Hawai'i, magma flux decreases, resulting in changes in eruptive volume, style, and composition. It is thought that melt storage becomes deeper and ephemeral with the transition from highly voluminous tholeiitic (shield stage) to the less voluminous alkaline (post-shield and rejuvenation stages) magmatism. To quantitatively test this, we applied high-precision fluid inclusion barometry via Raman spectroscopy to samples from representative...

CONCLUSIONS: Loss of drug subsidies after Medicaid disenrollment was associated with higher mortality among low-income Medicare beneficiaries. (Funded by the National Institute on Aging and others.).