Aging & Longevity

Implications of stress-induced gene expression for hematopoietic stem cell aging studies

1 month 1 week ago
A decline in hematopoietic stem cell (HSC) function is believed to underlie hematological shortcomings with age; however, a comprehensive molecular understanding of these changes is currently lacking. Here we provide evidence that a transcriptional signature reported in several previous studies on HSC aging is linked to stress-induced changes in gene expression rather than aging. Our findings have strong implications for the design and interpretation of HSC aging studies.
Anna Konturek-Ciesla

Adipose-tissue regulatory T cells are a consortium of subtypes that evolves with age and diet

1 month 1 week ago
Foxp3^(+)CD4^(+) regulatory T (Treg) cells found within tissues regulate local immunity, inflammation, and homeostasis. Tregs in epididymal visceral adipose tissue (eVAT) are critical regulators of local and systemic inflammation and metabolism. During aging and under obesogenic conditions, eVAT Tregs undergo transcriptional and phenotypic changes and are important for containing inflammation and normalizing metabolic indices. We have employed single-cell RNA sequencing, single-cell Tra and Trb...
Andrés R Muñoz-Rojas

Correlates of life course physical activity in participants of the Baltimore longitudinal study of aging

1 month 1 week ago
Physical activity is consistently associated with better health and longer life spans. However, the extent to which length and intensity of exercise across the life course impact health outcomes relative to current activity is undefined. Participants of the Baltimore Longitudinal Study of Aging were asked to categorize their level of physical activity in each decade of life from adolescence to the current decade. In linear mixed effects models, self-reported past levels of physical activity were...
Ann Zenobia Moore

Senolytic treatment alleviates doxorubicin-induced chemobrain

1 month 1 week ago
Doxorubicin (Dox), a widely used treatment for cancer, can result in chemotherapy-induced cognitive impairments (chemobrain). Chemobrain is associated with inflammation and oxidative stress similar to aging. As such, Dox treatment has also been used as a model of aging. However, it is unclear if Dox induces brain changes similar to that observed during aging since Dox does not readily enter the brain. Rather, the mechanism for chemobrain likely involves the induction of peripheral cellular...
Vivekananda Budamagunta

Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development

1 month 1 week ago
Heart failure (HF) causes substantial morbidity and mortality but its pathobiology is incompletely understood. The proteome is a promising intermediate phenotype for discovery of novel mechanisms. We measured 4877 plasma proteins in 13,900 HF-free individuals across three analysis sets with diverse age, geography, and HF ascertainment to identify circulating proteins and protein networks associated with HF development. Parallel analyses in Atherosclerosis Risk in Communities study participants...
Amil M Shah

Lipid droplets, autophagy, and ageing: A cell-specific tale

1 month 2 weeks ago
Lipid droplets are the essential organelle for storing lipids in a cell. Within the variety of the human body, different cells store, utilize and release lipids in different ways, depending on their intrinsic function. However, these differences are not well characterized and, especially in the context of ageing, represent a key factor for cardiometabolic diseases. Whole body lipid homeostasis is a central interest in the field of cardiometabolic diseases. In this review we characterize lipid...
Alice Maestri

Synergistic interplay of UV radiation and urban particulate matter induces impairment of autophagy and alters cellular fate in senescence-prone human dermal fibroblasts

1 month 2 weeks ago
Skin aging is a complex process influenced by intrinsic factors and environmental stressors, including ultraviolet (UV) radiation and air pollution, among others. In this study, we investigated the effects of UVA and UVB radiation, combined with urban particulate matter (UPM), on human dermal fibroblasts (HDF). We show here that treatment of HDF with a subcytotoxic dose of UVA/UVB results in a series of events leading to mitochondrial dysfunction, increased ROS levels, and DNA damage. These...
Lena Guerrero-Navarro

Cholesterol biosynthetic pathway induces cellular senescence through ERRα

1 month 2 weeks ago
Cellular senescence is a cell program induced by various stresses that leads to a stable proliferation arrest and to a senescence-associated secretory phenotype. Accumulation of senescent cells during age-related diseases participates in these pathologies and regulates healthy lifespan. Recent evidences point out a global dysregulated intracellular metabolism associated to senescence phenotype. Nonetheless, the functional contribution of metabolic homeostasis in regulating senescence is barely...
Dorian V Ziegler

Identification of aberrant luminal progenitors and mTORC1 as a potential breast cancer prevention target in BRCA2 mutation carriers

1 month 2 weeks ago
Inheritance of a BRCA2 pathogenic variant conveys a substantial life-time risk of breast cancer. Identification of the cell(s)-of-origin of BRCA2-mutant breast cancer and targetable perturbations that contribute to transformation remains an unmet need for these individuals who frequently undergo prophylactic mastectomy. Using preneoplastic specimens from age-matched, premenopausal females, here we show broad dysregulation across the luminal compartment in BRCA2^(mut/+) tissue, including...
Rachel Joyce

The forecasted prevalence of comorbidities and multimorbidity in people with HIV in the United States through the year 2030: A modeling study

1 month 2 weeks ago
CONCLUSIONS: The PEARL forecasts suggest a continued rise in comorbidity and multimorbidity prevalence to 2030, marked by heterogeneities across race/ethnicity, gender, and HIV acquisition risk subgroups. HIV clinicians must stay current on the ever-changing comorbidities-specific guidelines to provide guideline-recommended care. HIV clinical directors should ensure linkages to subspecialty care within the clinic or by referral. HIV policy decision-makers must allocate resources and support...
Keri N Althoff

Mathematical recapitulation of the end stages of human ovarian aging

1 month 2 weeks ago
Ovarian aging in women can be described as highly unpredictable within individuals but predictable across large populations. We showed previously that modeling an individual woman's ovarian reserve of primordial follicles using mathematical random walks replicates the natural pattern of growing follicles exiting the reserve. Compiling many simulations yields the observed population distribution of the age at natural menopause (ANM). Here, we have probed how stochastic control of primordial...
Sean D Lawley

OXR1 maintains the retromer to delay brain aging under dietary restriction

1 month 2 weeks ago
Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd, the fly homolog of OXR1, which influenced lifespan and mtd expression in response to DR. Knockdown in adulthood inhibited DR-mediated lifespan extension in female flies. We found that mtd/OXR1 expression declines with age and it interacts with the retromer, which regulates trafficking of proteins and lipids. Loss of mtd/OXR1 destabilized the retromer, causing improper protein trafficking...
Kenneth A Wilson

Cell type-specific regulation of m<sup>6</sup> A modified RNAs in the aging Drosophila brain

1 month 2 weeks ago
The aging brain is highly vulnerable to cellular stress, and neurons employ numerous mechanisms to combat neurotoxic proteins and promote healthy brain aging. The RNA modification m⁶ A is highly enriched in the Drosophila brain and is critical for the acute heat stress response of the brain. Here we examine m⁶ A in the fly brain with the chronic stresses of aging and degenerative disease. m⁶ A levels dynamically increased with both age and disease in the brain, marking integral neuronal identity...
Alexandra E Perlegos

Age-regulated cycling metabolites are relevant for behavior

1 month 2 weeks ago
Circadian cycles of sleep:wake and gene expression change with age in all organisms examined. Metabolism is also under robust circadian regulation, but little is known about how metabolic cycles change with age and whether these contribute to the regulation of behavioral cycles. To address this gap, we compared cycling of metabolites in young and old Drosophila and found major age-related variations. A significant model separated the young metabolic profiles by circadian timepoint, but could not...
Jessica E Schwarz

Nutritional regulation of microbiota-derived metabolites: Implications for immunity and inflammation

1 month 2 weeks ago
Nutrition profoundly shapes immunity and inflammation across the lifespan of mammals, from pre- and post-natal periods to later life. Emerging insights into diet-microbiota interactions indicate that nutrition has a dominant influence on the composition-and metabolic output-of the intestinal microbiota, which in turn has major consequences for host immunity and inflammation. Here, we discuss recent findings that support the concept that dietary effects on microbiota-derived metabolites potently...
Mohammad Arifuzzaman

TRIM22 induces cellular senescence by targeting PHLPP2 in hepatocellular carcinoma

1 month 2 weeks ago
The ubiquitin-proteasome system is a vital protein degradation system that is involved in various cellular processes, such as cell cycle progression, apoptosis, and differentiation. Dysregulation of this system has been implicated in numerous diseases, including cancer, vascular disease, and neurodegenerative disorders. Induction of cellular senescence in hepatocellular carcinoma (HCC) is a potential anticancer strategy, but the precise role of the ubiquitin-proteasome system in cellular...
Donghee Kang

Disruption of lysosomal proteolysis in astrocytes facilitates midbrain organoid proteostasis failure in an early-onset Parkinson's disease model

1 month 2 weeks ago
Accumulation of advanced glycation end products (AGEs) on biopolymers accompanies cellular aging and drives poorly understood disease processes. Here, we studied how AGEs contribute to development of early onset Parkinson's Disease (PD) caused by loss-of-function of DJ1, a protein deglycase. In induced pluripotent stem cell (iPSC)-derived midbrain organoid models deficient for DJ1 activity, we find that lysosomal proteolysis is impaired, causing AGEs to accumulate, α-synuclein (α-syn)...
Gustavo Morrone Parfitt
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