Aging & Longevity

No abstract

Cellular senescence is a key driver of age-related pathologies. Our study focuses on PTCHD4, a transmembrane protein with previously undefined physiological functions in aging processes. We found that PTCHD4 expression was increased across multiple cellular senescence models and showed an age-associated increase in mouse tissues and human lung transcriptomic datasets. Functionally, PTCHD4 deficiency attenuated senescence progression, whereas its overexpression promoted this process. In vivo,...

As societies age, a deeper understanding of ageing-related factors that contribute to longevity is needed. We therefore investigated possible longevity factors (social, medical, and biological) in relation to parental longevity (PL) and polygenic longevity scores (PGLSs). We examined 1126 70-year-olds from the Swedish population-based Gothenburg H70 Birth Cohort study in 2014-2016 (response rate 72%), with follow-up in 2019-2022 (response rate 77.6%). Comprehensive examinations included...

Long-term humoral immunity relies on long-lived plasma cells in the bone marrow (BM). However, the processes governing plasma cell transport, positioning, and longevity within the BM niche remain poorly understood, especially in humans. Most existing knowledge comes from mouse studies or limited human-based models, which makes translating findings to human biology challenging. Here, we introduce a physiologically relevant human bone marrow-on-a-chip (hBMOC) model to investigate the behavior and...

Ovarian aging leads to permanent reproductive senescence and systemic hormonal changes that predispose women to age-associated comorbidities. Despite these observations, the intrinsic mechanisms driving age-related ovarian decline are poorly defined. Mitochondrial DNA (mtDNA) mutations and instability are strongly associated with aging; however, it remains unknown if naturally occurring mitochondrial genetic variation influences the trajectory of ovarian aging. To address this, we compared two...

Ultraviolet (UV)-induced skin photoaging is driven by cellular senescence and chronic inflammation. Although the secretome (SCT) derived from human umbilical cord mesenchymal stem cells (hUC-MSC SCT) exhibits regenerative potential, its role in combating photoaging remains to be elucidated. In this study, we show that SCT markedly ameliorates photoaging in UV-exposed mice, restoring epidermal barrier function, dermal collagen integrity, senescence-associated markers, and systemic inflammatory...

Ecological theories predict a fundamental trade-off between fast growth and the probability of achieving longevity, with far-reaching consequences for ecosystem resilience and carbon residence time. Tree-ring studies have revealed a globally consistent negative relationship between growth rate and lifespan, yet comparable large-scale evidence for such trade-offs beyond trees remains scarce, largely due to methodological limitations. Here, we exploit annual growth rings formed by secondary...

Certain forms of mitochondrial impairment confer longevity, while disease-associated mitochondrial dysfunction triggers pathogenesis. The adaptive pathways that distinguish benefit from pathology remain unclear. Here we reveal that longevity induced by mitochondrial Complex I/nuo-6 mutation in C. elegans is dependent on the endoplasmic reticulum (ER) Ca^(2+) channel, InsP3R. To explain this connection, we test multiple candidate links between Ca^(2+) and mitochondrial homeostasis previously...

CONCLUSIONS AND IMPLICATIONS: Age and gender are critical modifiers of functional recovery after hip fracture. The vulnerability of 70 to 79 year olds and the increasing ADL disability during recovery of the oldest-old underscore the need for age-specific rehabilitation strategies in aging populations like China.

Senescent cells, which are normally cleared by the immune system but accumulate with age, contribute to multiple disorders including metabolic dysfunction and impaired fitness. While immune checkpoint inhibitors have been well studied in cancer, the role of programmed cell death ligand 2 (PD-L2) in non-cancerous, age-associated cellular senescence remains unclear. We found that PD-L2 is upregulated in isolated senescent human cells and during aging, and senolytics can remove age-associated,...

Population aging is accompanied by a rising burden of metabolic disorders, including obesity, type 2 diabetes (T2D), metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiovascular complications. Aging is also associated with broad remodeling of the immune system, characterized by reduced protective capacity together with persistent low-grade inflammatory activity, commonly discussed in terms of immunosenescence and inflammaging. In this narrative review, informed by a...

Insulin-like growth factor-1 (IGF-1) plays a crucial role in brain health and cognitive function, with levels varying across APOE genotypes, a major risk factor for Alzheimer's disease. Here, cross-lagged path modeling was used to examine longitudinal associations between IGF-1 levels, cognitive performance, and sociodemographic factors across APOE genotypes in 1247 older adults from the Rancho Bernardo Study of Healthy Aging. Distinct association patterns emerged across genotypes. Both IGF-1...

Blood pressure, muscle function and central adiposity are routinely measurable but are usually examined as separate risk domains. We analysed harmonised data from the China Health and Retirement Longitudinal Study (CHARLS), the English Longitudinal Study of Ageing (ELSA) and the Health and Retirement Study (HRS) to test whether a rule-based vascular-muscle-adiposity adverse-count phenotype was associated with incident stroke in middle-aged and older adults. The baseline analytic cohort included...

CONCLUSION: BZBS improved skeletal muscle mass and function, trabecular bone microarchitecture, and bone mechanical properties in female Ercc1^(+/-) mice and reduced the skeletal muscle expression of proteins associated with atrophy and senescence. These improvements may be associated with increased whole-body energy metabolism and spontaneous locomotor activity, as well as lower circulating levels of myostatin and FSH and higher levels of E2. These findings provide preclinical support for...

SUMOylation is a reversible post-translational modification increasingly recognized for its role in coordinating cellular responses to metabolic stress during aging. Emerging evidence indicates that it functions beyond a conventional modification, representing an adaptive stress‑responsive regulatory network that integrates metabolic, oxidative, inflammatory, and proteotoxic signals. Rather than acting on isolated pathways, this network finely tunes mitochondrial function, proteostasis, genome...

With advancing age comes declines in physical, cognitive, and cardiovascular function, leading to decreased performance in activities of daily living and eventual loss of independence. Exercise may delay this decline. High-intensity interval training (HIIT) consists of intense activity periods interspersed with bouts of active recovery. Previously, we demonstrated that HIIT preserved physical function in male mice across the lifespan. In the current work, we extend our prior investigations to...

Candidate biomarkers of biologic aging include p16^(INK4a) (p16) expression in peripheral blood T cells, a marker of cellular senescence, and whole-blood DNA methylation (DNAm) clocks, markers of epigenetic aging. Both have been associated with age-accelerating conditions, including cancer and chemotherapy, but their relationship has been inadequately studied. Biomarkers were evaluated in women with early breast cancer (n = 251) and non-cancer controls (n = 49). T-cell p16 expression and five...

Circulating folate, vitamin B12, and homocysteine reflect one-carbon (1-C) metabolism, a pathway central to methylation and cellular maintenance, but longitudinal evidence linking these biomarkers to biological aging remains limited, particularly in low- and middle-income populations. We examined associations of 1-C biomarkers with clinical biomarker-based Phenotypic Age and DNA methylation-based measures of accelerated biological aging among adults aged ≥ 60 years in the Longitudinal Aging...

CONCLUSIONS: In this multinational cohort, the findings revealed the associations of individual- and country-level factors with healthy working lives, underscoring the necessity for measures aimed at extending healthy working lives to align with country-specific social, economic and employment contexts. Besides, interventions targeting individual modifiable risk factors should be warranted through life-course.

Platinum-based drugs cause mutations and liver aging in children treated for cancer.