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Impact of immunosenescence and inflammaging on the effects of immune checkpoint inhibitors

Cancer Pathogenesis and Therapy 2024年第1期2卷 24-30页

作者： Chuandong Hou Zining Wang Xuechun Lu Medical School of Chinese PLA Beijing 100853China Department of Hematology The Second Medical Center&National Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijing 100853China

Immune checkpoint inhibitors(ICIs)are employed in immunotherapeutic applications for patients with weakened immune systems and can improve the ability of T cells to kill cancer cells.Although ICIs can potentially treat different types of cancers in various groups of patients,their effectiveness may differ among older individuals.The reason ICIs are less effective in older adults is not yet clearly understood,but age-related changes in the immune system,such as immunosenescence and inflammation,may play a role.Therefore,this review focuses on recent advances in understanding the effects of immunosenescence and inflammation on the efficacy of ICIs.

关键词： Immunosenescence inflammaging Immune checkpoint inhibitor

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Metabolic reprogramming in inflammaging and aging in T cells

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Life Metabolism 2023年第5期2卷 17-24页

作者： Alessio Bevilacqua Ping-Chih Ho Fabien Franco Department of Fundamental Oncology University of Lausanne1007 LausanneSwitzerland Ludwig Institute for Cancer Research University of Lausanne1066 EpalingesSwitzerland

Aging represents an emerging challenge for public health due to the declined immune responses against pathogens, weakened vaccination efficacy, and disturbed tissue homeostasis. Metabolic alterations in cellular and systemic levels are also known to be cardinal features of aging. Moreover, cellular metabolism has emerged to provide regulations to guide immune cell behavior via modulations on signaling cascades and epigenetic landscape, and the aberrant aging process in immune cells can lead to inflammaging, a chronic and low-grade inflammation that facilitates aging by perturbing homeostasis in tissues and organs. Here, we review how the metabolic program in T cells is influenced by the aging process and how aged T cells modulate inflammaging. In addition, we discuss the potential approaches to reverse or ameliorate aging by rewiring the metabolic programming of immune cells.

关键词： immunometabolism inflammaging T cells

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Estrogen rapid effects:a window of opportunity for the aging brain?

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Neural Regeneration Research 2022年第8期17卷 1629-1632页

作者： Ivanny Marchant Jana Stojanova Lilian Acevedo Pablo Olivero Laboratorio de Modelamiento en Medicina Escuela de MedicinaUniversidad de ValparaísoViña del MarChile Interdisciplinary Centre for Health Studies(CIESAL) Universidad de ValparaísoViña del MarChile Servicio de Neurología Hospital Carlos van Buren ValparaísoChile Laboratorio de Estructura y Función Celular Escuela de MedicinaFacultad de MedicinaUniversidad de ValparaísoValparaísoChile Centro Interoperativo en Ciencias Odontológicas y Médicas Universidad de ValparaísoValparaísoChile

Estrogen produces several beneficial effects in healthy neurological tissues and exhibits cardioprotective effects.Hormone therapy has been widely used to treat menopausal estrogen deficiency for more than 80 years.Despite high initial expectations of cardioprotective effects,there has been substantial distrust following important randomized clinical trials,such as the Women’s Health Initiative.Subsequently,the timing of treatment in relation to the onset of menopause came under consideration and led to the proposal of the timing hypothesis,that early initial treatment is important,and benefits are lost as the timing since menopause becomes prolonged.Subsequent analyses of the Women’s Health Initiative data,together with more recent data from randomized and observational trials,consistently show reductions in coronary heart disease and mortality in younger menopausal women.Regarding cognitive function,the timing hypothesis is consistent with observations from basic and animal studies.There is some clinical evidence to support the benefits of hormonal therapy in this context,though skepticism remains due to the paucity of clinical trials of substantial length in younger menopausal women.It is likely that the effects of estrogens on cognitive performance are due to rapid mechanisms,including mechanisms that influence Ca2+homeostasis dynamics,provide protection in a hostile environment and reduce inflammatory signals from neural tissues.In the future,inflammatory profiles accounting for early signs of pathological inflammation might help identify the‘window of opportunity’to use estrogen therapy for successful cognitive protection.

关键词： aging cardiovascular prevention cognitive function estrogen hormone treatment inflammaging rapid effects timing hypothesis TRPV1 window of opportunity

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Tissue-specific Gene Expression Changes Are Associated with Aging in Mice

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Genomics, Proteomics & Bioinformatics 2020年第4期18卷 430-442页

作者： Akash Srivastava Emanuel Barth Maria A.Ermolaeva Madlen Guenther Christiane Frahm Manja Marz Otto W.Witte Hans-Berger Department of Neurology University Hospital JenaFriedrich Schiller University Jena07747 JenaGermany Bioinformatics/High Throughput Analysis Friedrich Schiller University Jena07743 JenaGermany FLI Leibniz Institute for Age Research 07745 JenaGermany

Aging is a complex process that can be characterized by functional and cognitive decline in an individual. Aging can be assessed based on the functional capacity of vital organs and their intricate interactions with one another. Thus, the nature of aging can be described by focusing on a specific organ and an individual itself. However, to fully understand the complexity of aging,one must investigate not only a single tissue or biological process but also its complex interplay and interdependencies with other biological processes. Here, using RNA-seq, we monitored changes in the transcriptome during aging in four tissues(including brain, blood, skin and liver) in mice at9 months, 15 months, and 24 months, with a final evaluation at the very old age of 30 months.We identified several genes and processes that were differentially regulated during aging in both tissue-dependent and tissue-independent manners. Most importantly, we found that the electron transport chain(ETC) of mitochondria was similarly affected at the transcriptome level in the four tissues during the aging process. We also identified the liver as the tissue showing the largest variety of differentially expressed genes(DEGs) over time. Lcn2(Lipocalin-2) was found to be similarly regulated among all tissues, and its effect on longevity and survival was validated using its orthologue in Caenorhabditis elegans. Our study demonstrated that the molecular processes of aging are relatively subtle in their progress, and the aging process of every tissue depends on the tissue’s specialized function and environment. Hence, individual gene or process alone cannot be described as the key of aging in the whole organism.

关键词： Aging RNA-seq analysis inflammaging Electron transport chain Tissue aging

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The role of cofilin in age-related neuroinflammation

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Neural Regeneration Research 2020年第8期15卷 1451-1459页

作者： Amsha S.Alsegiani Zahoor A.Shah Department of Medicinal and Biological Chemistry College of Pharmacy and Pharmaceutical Sciences University of Toledo

Aging brain becomes susceptible to neurodegenerative diseases due to the shifting of microglia and astrocyte phenotypes to an active“pro-inflammatory”state,causing chronic low-grade neuroinflammation.Despite the fact that the role of neuroinflammation during aging has been extensively studied in recent years,the underlying causes remain unclear.The identification of relevant proteins and understanding their potential roles in neuroinflammation can help explain their potential of becoming biomarkers in the aging brain and as drug targets for prevention and treatment.This will eventually reduce the chances of developing neurodegenerative diseases and promote healthier lives in the elderly.In this review,we have summarized the morphological and cellular changes in the aging brain,the effects of age-related neuroinflammation,and the potential role of cofilin-1 during neuroinflammation.We also discuss other factors contributing to brain aging and neuroinflammation.

关键词： aging astrocyte-activation cofilin cofilin inhibitor cofilin/actin rods inflammaging microglial activation neurogenesis neuroinflammation

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Safe Retinol-Like Skin Biological Effect by a New Complex, Enriched with Retinol Precursors

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Journal of Cosmetics, Dermatological Sciences and Applications 2020年第2期10卷 59-75页

作者： Ze’evi Ma’or Dror Cohen Ya’ara La’or-Costa Meital Portugal-Cohen Ahava Dead Sea Laboratories Lod Israel The Skin Research Institute the Dead-Sea and Arava Science Center Masada Israel

Background: Retinol (RE) is deeply involved in skin processes, therefore it is widely formulated in cosmetics, primarily as an anti-aging ingredient. Despite its efficacy, the safety profile of RE is controversial. Objectives: Pretinol (PRE) complex was formulated with two RE precursors, β-Carotene and Niacinamide, in order to deliver retinol-like skin benefits with healthier characteristics, assuming that skin enzymes will enable safe RE supply on spot. Methods: The expression levels of hyaluronic acid, Tumor Necrosis Factor alpha (TNFα) and Interleukin 1 alpha (IL-1α), were measured using various skin models before and after exposure to PRE and RE. Full genome microarray was performed and the affected genes and pathways were analyzed. Results: Following fibroblasts exposure to PRE, the natural synthesis of hyaluronic acid is significantly elevated. Skin safety, demonstrated via cytokines expression on ex-vivo skin, results with TNFα and IL-1α elevation by RE application. In contrary PRE significantly reduces TNFα while IL-1α is not affected. These results establish skin safety advantage of PRE vs RE. Microarray results examined on skin equivalents reveal the involvement of PRE in inflammatory attenuation. Conclusions: Formulating RE precursors as a safe source for RE is partially supported. PRE presents a skin benefit in parallel to RE, while PRE characteristics are suggested to be safer to skin.

关键词： Retinol Hyaluronic Acid β-Carotene Skin inflammaging Irritation

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