Cellular senescence is a double-edged sword in regulating aged immune responses to influenza.

Clearance of senescent cells has demonstrated therapeutic potential in the context of chronic age-related diseases. Little is known, however, how clearing senescent cells affects the ability to respond to an acute infection and form quality immunological memory. We aimed to probe the effects of clearing senescent cells in aged mice on the immune response to influenza (flu) infection. We utilized a p16 trimodality reporter mouse model (p16-3MR) to allow for identification and selective clearance of p16-expressing cells upon administration of ganciclovir (GCV). While p16-expressing cells may exacerbate dysfunctional responses to a primary infection, our data suggest they may play a role in fostering memory cell generation. We demonstrate that although clearance of p16-expressing cells enhanced viral clearance, this also severely limited antibody production in the lungs of flu-infected aged mice. 30 days later, there were fewer flu-specific CD8 memory T cells and lower levels of flu-specific antibodies in the lungs of GCV-treated mice. Furthermore, GCV-treated mice were unable to mount an optimal memory response and demonstrated increased viral load following heterosubtypic challenge. These results suggest that targeting senescent cells may potentiate primary responses while limiting the ability to form durable and protective immune memory with age.

In vivo structural connectivity of the reward system along the hippocampal long axis.

Recent work has identified a critical role for the hippocampus in reward-sensitive behaviors, including motivated memory, reinforcement learning, and decision-making. Animal histology and human functional neuroimaging have shown that brain regions involved in reward processing and motivation are more interconnected with the ventral/anterior hippocampus. However, direct evidence examining gradients of structural connectivity between reward regions and the hippocampus in humans is lacking. The present study used diffusion MRI (dMRI) and probabilistic tractography to quantify the structural connectivity of the hippocampus with key reward processing regions in vivo. Using a large sample of subjects (N = 628) from the human connectome dMRI data release, we found that connectivity profiles with the hippocampus varied widely between different regions of the reward circuit. While the dopaminergic midbrain (ventral tegmental area) showed stronger connectivity with the anterior versus posterior hippocampus, the ventromedial prefrontal cortex showed stronger connectivity with the posterior hippocampus. The limbic (ventral) striatum demonstrated a more homogeneous connectivity profile along the hippocampal long axis. This is the first study to generate a probabilistic atlas of the hippocampal structural connectivity with reward-related networks, which is essential to investigating how these circuits contribute to normative adaptive behavior and maladaptive behaviors in psychiatric illness. These findings describe nuanced structural connectivity that sets the foundation to better understand how the hippocampus influences reward-guided behavior in humans.

Evolutionary history influences the microbiomes of a female symbiotic reproductive organ in cephalopods.

Many female squids and cuttlefishes have a symbiotic reproductive organ called the accessory nidamental gland (ANG) that hosts a bacterial consortium involved with egg defense against pathogens and fouling organisms. While the ANG is found in multiple cephalopod families, little is known about the global microbial diversity of these ANG bacterial symbionts. We used 16S rRNA gene community analysis to characterize the ANG microbiome from different cephalopod species and assess the relationship between host and symbiont phylogenies. The ANG microbiome of 11 species of cephalopods from four families (superorder: Decapodiformes) that span seven geographic locations was characterized. Bacteria of class Alphaproteobacteria, Gammaproteobacteria, and Flavobacteriia were found in all species, yet analysis of amplicon sequence variants by multiple distance metrics revealed a significant difference between ANG microbiomes of cephalopod families (weighted/unweighted UniFrac, Bray-Curtis, P = 0.001). Despite being collected from widely disparate geographic locations, members of the family Sepiolidae (bobtail squid) shared many bacterial taxa including (~50%) Opitutae (Verrucomicrobia) and Ruegeria (Alphaproteobacteria) species. Furthermore, we tested for phylosymbiosis and found a positive correlation between host phylogenetic distance and bacterial community dissimilarity (Mantel test r = 0.7). These data suggest that closely related sepiolids select for distinct symbionts from similar bacterial taxa. Overall, the ANGs of different cephalopod species harbor distinct microbiomes and thus offer a diverse symbiont community to explore antimicrobial activity and other functional roles in host fitness.IMPORTANCEMany aquatic organisms recruit microbial symbionts from the environment that provide a variety of functions, including defense from pathogens. Some female cephalopods (squids, bobtail squids, and cuttlefish) have a reproductive organ called the accessory nidamental gland (ANG) that contains a bacterial consortium that protects eggs from pathogens. Despite the wide distribution of these cephalopods, whether they share similar microbiomes is unknown. Here, we studied the microbial diversity of the ANG in 11 species of cephalopods distributed over a broad geographic range and representing 15-120 million years of host divergence. The ANG microbiomes shared some bacterial taxa, but each cephalopod species had unique symbiotic members. Additionally, analysis of host-symbiont phylogenies suggests that the evolutionary histories of the partners have been important in shaping the ANG microbiome. This study advances our knowledge of cephalopod-bacteria relationships and provides a foundation to explore defensive symbionts in other systems.

Comparative cardiotoxicity assessment of bisphenol chemicals and estradiol using human induced pluripotent stem cell-derived cardiomyocytes.

Bisphenol A (BPA) is commonly used to manufacture consumer and medical-grade plastics. Due to health concerns, BPA substitutes are being incorporated-including bisphenol S (BPS) and bisphenol F (BPF)-without a comprehensive understanding of their toxicological profile. Previous studies suggest that bisphenol chemicals perturb cardiac electrophysiology in a manner that is similar to 17ß-estradiol (E2). We aimed to compare the effects of E2 with BPA, BPF, and BPS using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Cardiac parameters were evaluated using microelectrode array (MEA) technology and live-cell fluorescent imaging. Cardiac metrics remained relatively stable after exposure to nanomolar concentrations (1-1000 nM) of E2, BPA, BPF, or BPS. At higher micromolar concentrations, chemical exposures decreased the depolarization spike amplitude, and shortened the field potential, action potential duration, and calcium transient duration (E2 ≥ BPA ≥ BPF ≫ BPS). Cardiomyocyte physiology was largely undisturbed by BPS. BPA-induced effects were exaggerated when coadministered with an L-type calcium channel (LTCC) antagonist or E2, and reduced when coadministered with an LTCC agonist or an estrogen receptor alpha antagonist. E2-induced effects were not exaggerated by coadministration with an LTCC antagonist. Although the observed cardiac effects of E2 and BPA were similar, a few distinct differences suggest that these chemicals may act (in part) through different mechanisms. hiPSC-CM are a useful model for screening cardiotoxic chemicals, nevertheless, the described findings should be validated using a more complex ex vivo and/or in vivo model.

Mothers' and fathers' depressive symptoms across four years postpartum: An examination of between- and bidirectional within-person relations.

BACKGROUND: Both mothers and fathers are at risk for experiencing postpartum depressive symptoms shortly after the birth of a child. Previous studies suggest mothers' and fathers' depressive symptoms to be interrelated. This study examined bidirectional relations between mothers' and fathers' depressive symptoms across four years postpartum. METHODS: Longitudinal data for this study were collected across five waves from 485 mothers and 359 fathers of infants when infants were on average 6 months-old until children were 54 months-old (1-year lags). Mothers and fathers reported on their depressive symptoms using the Center for the Epidemiological Studies Short Depression Scale (CES-D 10). A random intercept cross-lagged panel model (RICLPM) was specified to examine the bidirectional relations between mothers' and fathers' depressive symptoms over time. RESULTS: At the between-person level, mothers' and fathers' depressive symptoms were positively associated. At the within-person level, unique carry-over effects were found for mothers and fathers in that when reporting higher depressive symptoms than their trait levels, they were more likely to report higher depressive symptoms one year later. Moreover, intermittent cross-lagged effects were observed from mothers' depressive symptoms to fathers' depressive symptoms during toddlerhood. LIMITATIONS: The sample was not racially or structurally diverse thereby limiting the generalizations of the findings. CONCLUSIONS: After the birth of a child, mothers and fathers are at risk for experiencing chronic depressive symptoms which can have implications for individual, couple and child health. Mothers' depressive symptoms are related to fathers' depressive symptoms over time.

Outcomes and outcome measures utilised in randomised controlled trials of postoperative caesarean delivery pain: a scoping review.

BACKGROUND: Inadequately treated postoperative pain following caesarean delivery can delay recovery and the ability to care for a newborn. Effectiveness studies of interventions to treat postoperative caesarean delivery pain measure different outcomes, limiting data pooling for meta-analysis. We performed a comprehensive review of existing outcomes with the aim of recommending core outcomes for future research. METHODS: A scoping review to identify all outcomes reported in randomised controlled trials (RCTs) and clinical trial registries of interventions to treat or prevent postoperative caesarean delivery pain, with postoperative pain as a primary outcome measure. We searched PubMed, Web of Science, CINAHL, LILACS, Embase, CDSR and CRCT for studies from May 2016 to 2021. Outcomes were extracted and frequencies tabulated. RESULTS: Ninety RCTs and 11 trial registries were included. In total, 392 outcomes (375 inpatient and 17 outpatient) were identified and categorised. The most reported outcome domain was analgesia (n = 242/375, 64.5%), reported in 96% of inpatient studies, with analgesic consumption accounting for 108/375, 28.8% of analgesia outcomes. The second most common domain was pain intensity (n = 120/375, 32%), reported in 97% of inpatient studies, using the visual analogue scale (68/120, 59%) and the numerical reporting scale (37/120, 25%). Maternal and neonatal adverse effects accounted for 65/375 (17.3%) and 19/375 (5.1%) of inpatient outcomes, respectively. CONCLUSIONS: Outcomes reported in RCTs for postoperative caesarean delivery pain vary widely. The results of this review suggest that standardisation is needed to promote research efficiency and aid future meta-analyses to identify optimal postoperative caesarean delivery pain management.

Registry-derived stage (RD-Stage) for capturing cancer stage at diagnosis for endometrial cancer.

BACKGROUND: Capture of cancer stage at diagnosis is important yet poorly reported by health services to population-based cancer registries. In this paper we describe current completeness of stage information for endometrial cancer available in Australian cancer registries; and develop and validate a set of rules to enable cancer registry medical coders to calculate stage using data available to them (registry-derived stage or 'RD-Stage'). METHODOLOGY: Rules for deriving RD-stage (Endometrial carcinoma) were developed using the American Joint Commission on Cancer (AJCC) TNM (tumour, nodes, metastasis) Staging System (8th Edition). An expert working group comprising cancer specialists responsible for delivering cancer care, epidemiologists and medical coders reviewed and endorsed the rules. Baseline completeness of data fields required to calculate RD-Stage, and calculation of the proportion of cases for whom an RD stage could be assigned, was assessed across each Australian jurisdiction. RD-Stage (Endometrial cancer) was calculated by Victorian Cancer Registry (VCR) medical coders and compared with clinical stage recorded by the patient's treating clinician and captured in the National Gynae-Oncology Registry (NGOR). RESULTS: The necessary data completeness level for calculating RD-Stage (Endometrial carcinoma) across various Australian jurisdictions varied from 0 to 89%. Three jurisdictions captured degree of spread of cancer, rendering RD-Stage unable to be calculated. RD-Stage (Endometrial carcinoma) could not be derived for 64/485 (13%) cases and was not captured for 44/485 (9%) cases in NGOR. At stage category level (I, II, III, IV), there was concordance between RD-Stage and NGOR captured stage in 393/410 (96%) of cases (95.8%, Kendall's coefficient = 0.95). CONCLUSION: A lack of consistency in data captured by, and data sources reporting to, population-based cancer registries meant that it was not possible to provide national endometrial carcinoma stage data at diagnosis. In a sample of Victorian cases, where surgical pathology was available, there was very good concordance between RD-Stage (Endometrial carcinoma) and clinician-recorded stage data available from NGOR. RD-Stage offers promise in capturing endometrial cancer stage at diagnosis for population epidemiological purposes when it is not provided by health services, but requires more extensive validation.

Coral reefs in peril in a record-breaking year.

Climate change and its impacts on coral reefs have reached unchartered territory.

Impact of senolytic treatment on immunity, aging, and disease.

Cellular senescence has been implicated in the pathophysiology of many age-related diseases. However, it also plays an important protective role in the context of tumor suppression and wound healing. Reducing senescence burden through treatment with senolytic drugs or the use of genetically targeted models of senescent cell elimination in animals has shown positive results in the context of mitigating disease and age-associated inflammation. Despite positive, albeit heterogenous, outcomes in clinical trials, very little is known about the short-term and long-term immunological consequences of using senolytics as a treatment for age-related conditions. Further, many studies examining cellular senescence and senolytic treatment have been demonstrated in non-infectious disease models. Several recent reports suggest that senescent cell elimination may have benefits in COVID-19 and influenza resolution and disease prognosis. In this review, we discuss the current clinical trials and pre-clinical studies that are exploring the impact of senolytics on cellular immunity. We propose that while eliminating senescent cells may have an acute beneficial impact on primary immune responses, immunological memory may be negatively impacted. Closer investigation of senolytics on immune function and memory generation would provide insight as to whether senolytics could be used to enhance the aging immune system and have potential to be used as therapeutics or prophylactics in populations that are severely and disproportionately affected by infections such as the elderly and immunocompromised.

Comparative cardiotoxicity assessment of bisphenol chemicals and estradiol using human induced pluripotent stem cell-derived cardiomyocytes.

Background: Bisphenol A (BPA) is commonly used to manufacture consumer and medical-grade plastics. Due to health concerns, BPA substitutes are being incorporated - including bisphenol S (BPS) and bisphenol F (BPF) - without a comprehensive understanding of their toxicological profile. Objective: Previous studies suggest that bisphenol chemicals perturb cardiac electrophysiology in a manner that is similar to 17ß-estradiol (E2). We aimed to compare the effects of E2 with BPA, BPF, and BPS using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Methods: Cardiac parameters were evaluated using microelectrode array (MEA) technology and live-cell fluorescent imaging at baseline and in response to chemical exposure (0.001-100 µM). Results: Cardiac metrics remained relatively stable after exposure to nanomolar concentrations (1-1,000 nM) of E2, BPA, BPF, or BPS. At higher micromolar concentrations, chemical exposures resulted in a decrease in the depolarizing spike amplitude, shorter field potential and action potential duration, shorter calcium transient duration, and decrease in hiPSC-CM contractility (E2 > BPA > BPF >> BPS). Cardiomyocyte physiology was largely undisturbed by BPS exposure. BPA-induced effects were exaggerated when co-administered with an L-type calcium channel antagonist (verapamil) or E2 - and reduced when co-administered with an L-type calcium channel agonist (Bay K8644) or an estrogen receptor alpha antagonist (MPP). E2-induced effects generally mirrored those of BPA, but were not exaggerated by co-administration with an L-type calcium channel antagonist. Discussion: Collectively across multiple cardiac endpoints, E2 was the most potent and BPS was the least potent disruptor of hiPSC-CM function. Although the observed cardiac effects of E2 and BPA were similar, a few distinct differences suggest that these chemicals may act (in part) through different mechanisms. hiPSC-CM are a useful model for screening cardiotoxic chemicals, nevertheless, the described in vitro findings should be validated using a more complex ex vivo and/or in vivo model.

Senolytic treatment with dasatinib and quercetin does not improve overall influenza responses in aged mice.

Age is the greatest risk factor for adverse outcomes following influenza (flu) infection. The increased burden of senescent cells with age has been identified as a root cause in many diseases of aging and targeting these cells with drugs termed senolytics has shown promise in alleviating many age-related declines across organ systems. However, there is little known whether targeting these cells will improve age-related deficits in the immune system. Here, we utilized a well characterized senolytic treatment with a combination of dasatinib and quercetin (D + Q) to clear aged (18-20 months) mice of senescent cells prior to a flu infection. We comprehensively profiled immune responses during the primary infection as well as development of immune memory and protection following pathogen reencounter. Senolytic treatment did not improve any aspects of the immune response that were assayed for including: weight loss, viral load, CD8 T-cell infiltration, antibody production, memory T cell development, or recall ability. These results indicate that D + Q may not be an appropriate senolytic to improve aged immune responses to flu infection.

Adolescent Independent Eating Occasions, Dietary Intake, and Parenting Practices During the COVID-19 Pandemic: A Qualitative Study of Parents and Adolescents From Households With Low Income.

OBJECTIVE: Examine how experiencing the coronavirus disease 2019 (COVID-19) pandemic influenced adolescent independent eating occasions (iEOs) and iEO-related parenting practices from the perspective of parents and adolescents METHODS: Cross-sectional remote interviews were conducted for this basic qualitative research study. Participants were a purposive sample of multiracial/ethnic adolescents aged 11-14 years and their parents from households with low income (n = 12 dyads) representing 9 US states. The main outcome measures were iEOs and iEO-related parenting practices. Data were analyzed using directed content analysis. RESULTS: About half of the parents indicated that their adolescents had more iEOs during the COVID-19 pandemic and that there were changes in the types of foods consumed during iEOs. In contrast, most adolescents indicated their iEOs had not changed remarkably in frequency or foods consumed since the onset of the pandemic. Most parents reported no change in how they taught their adolescents about healthy food, the rules for foods/beverages permitted during iEOs, or how they monitored what their adolescents ate during iEOs; adolescent reports were in general agreement. Most parents indicated that family members were home together more often during the pandemic, which increased cooking frequency. CONCLUSIONS AND IMPLICATIONS: The effect of the COVID-19 pandemic on adolescents' iEOs varied, and the parenting practices used to influence iEOs remained stable during the pandemic. Families experienced having more time together and cooking at home more often.

Barriers to Healthy Family Dinners and Preventing Child Obesity: Focus Group Discussions with Parents of 5-to-8-Year-Old Children.

BACKGROUND: Although numerous physical and mental health benefits for children have been linked to family dinners, many families still do not have regular family meals together. This study sought to identify the barriers that keep families from having dinners together. METHODS: We interviewed 42 parents of 5-to-8-year-old children in small focus groups to identify barriers and challenges that keep families from having healthy and consistent dinners together. RESULTS: Parents reported the main barriers were time (e.g., time strain and overscheduling, mismatched schedules, long work hours, etc.), lack of meal planning or failure to follow plans, lack of skills (e.g., cooking skills or nutritional awareness), external factors (e.g., daycare, schools, or extended family, and competing with advertising), and food-related challenges (e.g., picky eating, food allergies). Parents also suggested potential solutions to overcome these barriers. CONCLUSIONS: Overall, parents had a desire to have family dinners with their children, but they felt that there are many barriers keeping them from establishing or maintaining consistent family mealtimes. Future research, as well as child obesity prevention and intervention efforts, should consider these barriers and suggested solutions in efforts to promote healthy and consistent family meals as a means of lowering the prevalence of childhood obesity.

Other treatments for CSP.

Caesarean scar pregnancy (CSP) is an increasingly common clinical conundrum. The non-curettage surgical management of CSP can be categorised into hysteroscopic, vaginal, laparoscopic, and open removal modalities and the choice of treatment is surgeon-dependent. A systematic review of original studies reporting surgical treatment outcomes of CSP until March 2023 was conducted to evaluate the non-curettage surgical management of this highly morbid condition. A total of 60 studies of mostly weak methodological quality were identified involving 6720 CSP cases. Success rates were generally high across all treatment modalities although highest in vaginal and laparoscopic excisional approaches. Morbidity was most associated with haemorrhage although unplanned hysterectomy rates remained low across all treatment groups. Subsequent pregnancies are associated with morbidity despite being underreported and the impact of CSP treatment on future pregnancy is poorly understood. Substantive study heterogeneity precludes meta-analyses of pooled data and treatment superiority has not been demonstrated.

Activities and social contact as antecedents to sleep onset time in U.S. adolescents.

This study evaluated adolescents' evening patterns in activities, social contact, and location to better understand antecedents to adolescents' sleep onset time (SOT). The SOT is important for sleep duration and related health outcomes. Using a nationally representative sample of 15- to 18-year-old adolescents from the American Time Use Survey (N = 10,341; 47% female; 57% white), structural equation modeling demonstrated that late SOTs mediated links between evening activities, social contact, locations, and shorter sleep durations. Passive leisure, time in public locations, and time with friends late in the evenings were associated with later SOTs, whereas homework and active leisure did not. Parents and practitioners can use this information to carefully evaluate evening activities, social contact, and location to support healthy SOTs for adolescents across time.

The effect of metformin on influenza vaccine responses in nondiabetic older adults: a pilot trial.

BACKGROUND: Aging is associated with progressive declines in immune responses leading to increased risk of severe infection and diminished vaccination responses. Influenza (flu) is a leading killer of older adults despite availability of seasonal vaccines. Geroscience-guided interventions targeting biological aging could offer transformational approaches to reverse broad declines in immune responses with aging. Here, we evaluated effects of metformin, an FDA approved diabetes drug and candidate anti-aging drug, on flu vaccination responses and markers of immunological resilience in a pilot and feasibility double-blinded placebo-controlled study. RESULTS: Healthy older adults (non-diabetic/non-prediabetic, age: 74.4 ± 1.7 years) were randomized to metformin (n = 8, 1500 mg extended release/daily) or placebo (n = 7) treatment for 20 weeks and were vaccinated with high-dose flu vaccine after 10 weeks of treatment. Peripheral blood mononuclear cells (PBMCs), serum, and plasma were collected prior to treatment, immediately prior to vaccination, and 1, 5, and 10 weeks post vaccination. Increased serum antibody titers were observed post vaccination with no significant differences between groups. Metformin treatment led to trending increases in circulating T follicular helper cells post-vaccination. Furthermore, 20 weeks of metformin treatment reduced expression of exhaustion marker CD57 in circulating CD4 T cells. CONCLUSIONS: Pre-vaccination metformin treatment improved some components of flu vaccine responses and reduced some markers of T cell exhaustion without serious adverse events in nondiabetic older adults. Thus, our findings highlight the potential utility of metformin to improve flu vaccine responses and reduce age-related immune exhaustion in older adults, providing improved immunological resilience in nondiabetic older adults.

Parenting Practices Are Associated With Adolescent Food Choices During Independent Eating Occasions.

BACKGROUND: Frequency of independent eating occasions (iEOs) has been linked to intake of unhealthy foods and overweight or obesity among adolescents. Parenting practices involving modeling healthy food intake and making healthy foods available have been associated with healthy food intake among adolescents; however, little is known about these associations during iEOs. OBJECTIVE: To determine whether parenting practices involving structure (monitoring, availability, modeling, and expectations), lack of structure (indulgence), and autonomy support reported by adolescents or parents were associated with adolescent iEO intake of junk foods, sugar-sweetened beverages (SSBs), sugary foods, and fruit and vegetables. DESIGN: Cross-sectional study measuring parenting practices and adolescent iEO food choices via an online survey and adapted food frequency questionnaire. PARTICIPANTS/SETTING: Parent/adolescent dyads (n = 622) completed surveys (November-December 2021) using a national Qualtrics panel database. Adolescents were 11 to 14 years of age and had iEOs at least weekly. MAIN OUTCOME MEASURES: Primary measures included parent- and adolescent-reported frequency of food parenting practices and adolescent-reported iEO intake of junk foods, sugary foods, SSBs, and fruits and vegetables. STATISTICAL ANALYSES PERFORMED: Multivariable linear regression models were used to examine associations between parenting practices and iEO intake of foods/beverages, adjusting for adolescent's age, sex, race and ethnicity, iEO frequency, parent's education and marital status, and household food security status. Bonferroni multiple comparison corrections were conducted. RESULTS: More than half of parents were female (66%) and 35 to 64 years of age (58%). Adolescents/parents identified as White/Caucasian (44%/42%), Black/African American (28%/27%), Asian (21%/23%), and Hispanic ethnicity (42%/42%). Positive associations were observed among adolescent-reported and parent-reported autonomy support, monitoring, indulgence and expectations parenting practices, and adolescent-reported daily iEO intake frequencies of junk foods, sugary foods, and fruits and vegetables (P < 0.001). CONCLUSIONS: Structural and autonomy support parenting practices were positively associated with both healthy and unhealthy iEO food intake by adolescents. Interventions to improve adolescent iEO intake could promote positive practices associated with healthy food consumption.

Cellular Senescence is a Double-Edged Sword in Regulating Aged Immune Responses to Influenza.

Clearance of senescent cells has demonstrated therapeutic potential in the context of chronic age-related diseases. Little is known, however, how clearing senescent cells affects the ability to respond to an acute infection and form quality immunological memory. We aimed to probe the effects of clearing senescent cells in aged mice on the immune response to influenza (flu) infection. We utilized a p16 trimodality reporter mouse model (p16-3MR) to allow for identification and selective deletion of p16-expressing senescent cells upon administration of ganciclovir (GCV). While p16-expressing senescent cells may exacerbate dysfunctional responses to a primary infection, our data suggest they may play a role in fostering memory cell generation. We demonstrate that although deletion of p16-expressing cells enhanced viral clearance, this also severely limited antibody production in the lungs of flu-infected aged mice. 30 days later, there were fewer flu-specific CD8 memory T cells and lower levels of flu-specific antibodies in the lungs of GCV treated mice. GCV treated mice were unable to mount an optimal memory response and demonstrated increased viral load following a heterosubtypic challenge. These results suggest that targeting senescent cells may potentiate primary responses while limiting the ability to form durable and protective immune memory with age.