The convergence of senescence and nutrient sensing during lymphocyte ageing

Immunosurveillance requires the migration of lymphocytes and their activation to induce proliferation and effector function. Effective immunity requires an optimal supply of nutrients to lymphocytes. Cells contain nutrient sensing apparatus such as adenosine 5′-monophosphate-activated protein kinase (AMPK) that surveys intracellular ATP levels. Immunity declines during ageing and one possibility is that the energy balance may be altered in old lymphocytes. This paper summarizes recent data identifying a convergence of senescence and nutrient signalling pathways in lymphocytes that inhibit both T cell and natural killer (NK) cell function during ageing. Significantly, these pathways can be inhibited to enhance the activity of these cells

Induction of T Cell Senescence by Cytokine Induced Bystander Activation

As people around the world continue to live longer, maintaining a good quality of life is of increasing importance. The COVID-19 pandemic revealed that the elderly are disproportionally vulnerable to infectious diseases and Immunosenescence plays a critical role in that. An ageing immune system influences the conventional activity of T cells which are at the forefront of eliminating harmful foreign antigens. With ageing, unconventional end-stage T cells, that exhibit a senescent phenotype, amass. These senescent T cells deviate from T cell receptor (TCR) signaling toward natural killer (NK) activity. The transition toward innate immune cell function from these adaptor T cells impacts antigen specificity, contributing to increased susceptibility of infection in the elderly. The mechanism by which senescent T cells arise remains largely unclear however in this review we investigate the part that bystander activation plays in driving the change in function of T cells with age. Cytokine-induced bystander activation may offer a plausible explanation for the induction of NK-like activity and senescence in T cells. Further understanding of these specific NK-like senescent T cells allows us to identify the benefits and detriments of these cells in health and disease which can be utilized or regulated, respectively. This review discusses the dynamic of senescent T cells in adopting NK-like T cells and the implications that has in an infectious disease context, predominately in the elderly

Targeting Inflammation and Immunosenescence to Improve Vaccine Responses in the Elderly

One of the most appreciated consequences of immunosenescence is an impaired response to vaccines with advanced age. While most studies report impaired antibody responses in older adults as a correlate of vaccine efficacy, it is now widely appreciated that this may fail to identify important changes occurring in the immune system with age that may affect vaccine efficacy. The impact of immunosenescence on vaccination goes beyond the defects on antibody responses as T cell-mediated responses are reshaped during aging and certainly affect vaccination. Likewise, age-related changes in the innate immune system may have important consequences on antigen presentation and priming of adaptive immune responses. Importantly, a low-level chronic inflammatory status known as inflammaging has been shown to inhibit immune responses to vaccination and pharmacological strategies aiming at blocking baseline inflammation can be potentially used to boost vaccine responses. Yet current strategies aiming at improving immunogenicity in the elderly have mainly focused on the use of adjuvants to promote local inflammation. More research is needed to understand the role of inflammation in vaccine responses and to reconcile these seemingly paradoxical observations. Alternative approaches to improve vaccine responses in the elderly include the use of higher vaccine doses or alternative routes of vaccination showing only limited benefits. This review will explore novel targets and potential new strategies for enhancing vaccine responses in older adults, including the use of anti-inflammatory drugs and immunomodulators

Senescent T cells: Beneficial and detrimental roles

As the thymus involutes during aging, the T-cell pool has to be maintained by the periodic expansion of preexisting T cells during adulthood. A conundrum is that repeated episodes of activation and proliferation drive the differentiation of T cells toward replicative senescence, due to telomere erosion. This review discusses mechanisms that regulate the end-stage differentiation (senescence) of T cells. Although these cells, within both CD4 and CD8 compartments, lose proliferative activity after antigen-specific challenge, they acquire innate-like immune function. While this may confer broad immune protection during aging, these senescent T cells may also cause immunopathology, especially in the context of excessive inflammation in tissue microenvironments

The role of senescent T cells in immunopathology

The development of senescence in tissues of different organs and in the immune system are usually investigated independently of each other although during ageing, senescence in both cellular systems develop concurrently. Senescent T cells are highly inflammatory and secrete cytotoxic mediators and express natural killer cells receptors (NKR) that bypass their antigen specificity. Instead they recognize stress ligands that are induced by inflammation or infection of different cell types in tissues. In this article we discuss data on T cell senescence, how it is regulated and evidence for novel functional attributes of senescent T cells. We discuss an interactive loop between senescent T cells and senescent non-lymphoid cells and conclude that in situations of intense inflammation, senescent cells may damage healthy tissue. While the example for immunopathology induced by senescent cells that we highlight is cutaneous leishmaniasis, this situation of organ damage may apply to other infections, including COVID-19 and also rheumatoid arthritis, where ageing, inflammation and senescent cells are all part of the same equation

Differing HLA types influence inhibitory receptor signalling in CMV-specific CD8+ T cells.

The dysregulated immune response to CMV constitutes a major force driving T cell immunosenescence and growing evidence suggests that it is not a benign virus in old age. We show here that the PD-1/L pathway defines a reversible defect in CMV specific CD8(+) T cell proliferative responses in both young and old individuals. More specifically, highly differentiated CD45RA(+)CD27(-) CMV-specific CD8(+) T cells exhibit a proliferative deficit compared their central and effector memory counterparts, which is reversed following PD-L blockade. However, we also report that HLA-B(∗)07/TPR specific CD8(+) T cells express higher levels of PD-1 than HLA-A(∗)02/NLV specific cells and HLA-A(∗)02 individuals show a higher proliferative response to PD-L blockade, than HLA-B(∗)07 individuals, which we postulate may be due to the differing functional avidities for these two CMV-specific CD8(+) T cells populations. Nevertheless data presented here demonstrate that CMV-specific CD8(+) T cells can be functionally enhanced by perturbation of the PD-1/L signalling pathway, whose manipulation may provide a therapeutic modality to combat age-associated immune decline

MEMBANGUN KESADARAN PELESTARIAN BIODIVERSITAS MELALUI FOTOGRAFI DI KALANGAN SISWA SMA/MA

Abstrak: Pembelajaran biodiversitas di sekolah menjadi salah satu pembekalan siswa terhadap pemahaman pentingnya pelestarian biodiversitas. Di jenjang SMA, materi biodiversitas telah diperoleh dari kelas X. Namun pembelajarannya masih terbatas pada ranah kognitif, sedangkan ranah afektif atau perilaku masih kurang dituntut. Metode konvensional seperti ceramah dan diskusi turut menyebabkan siswa merasa kurang tertarik untuk memahami pentingnya biodiversitas. Oleh karena itu, dengan metode fotografi diharapkan dapat menumbuhkan semangat konservasi dan pelestarian karena siswa mendokumentasikan makhluk hidup yang berada di sekitar lingkungannya. Tahapan kegiatan meliputi (1) memberikan pretest untuk mengidentifikasi sikap terhadap biodiversitas dalam keseharian, (2) menyampaikan materi secara daring terkait dasar fotografi, teknik fotografi flora dan fauna, serta keberagaman biodiversitas hewan dan tumbuhan, (3) praktik pengambilan foto objek hewan dan tumbuhan yang dikirimkan ke WhatsApp Group, (4) pemateri menelaah foto-foto dan memberikan penilaian serta saran terkait teknik fotografi, dan (5) memberikan posttest untuk ditelusuri kembali sikap yang mungkin muncul terhadap biodiversitas. Hasil yang diperoleh yaitu adanya peningkatan hingga 100% pada beberapa sikap terhadap biodiversitas, yaitu siswa tidak mau mengkonsumsi hewan yang dilindungi, tidak akan pernah membunuh hewan yang dilindungi, tidak akan pernah memetik tanaman/bunga yang dilindungi, dan menolak melakukan jual beli hewan dan tumbuhan yang dilindungi. Siswa juga telah mampu memberikan foto terbaiknya berdasarkan penilaian pemateri. Dengan demikian diharapkan siswa mampu menyampaikan pesan konservasi biodiversitas melalui karya fotonya.  Abstract: Biodiversity learning in schools is one of the supplies for students to understand the importance of biodiversity conservation. In high school, biodiversity subjects have been obtained from tenth grade. However, learning is still limited to the cognitive domain, while the affective or behavioural domains are still less demanded. Conventional methods such as lectures and discussions also cause students to feel less interested in understanding the importance of biodiversity. Therefore, the photography method is expected to foster a spirit of conservation and preservation because students document living things around their environment. The activity stages include (1) giving a pretest to identify attitudes towards biodiversity in daily life, (2) providing online subjects related to basic photography, flora and fauna photography techniques, and diversity of animal and plant biodiversity, (3) the practice of taking photos of animal and plant objects sent to the WhatsApp groups, (4) the trainers reviewing the photos and provide assessments and suggestions related to photography techniques, and (5) giving a posttest to retrace attitudes that may arise towards biodiversity. The results obtained are an increase of up to 100% in some attitudes towards biodiversity, namely students do not want to consume protected animals, will never kill protected animals, will never pick protected plants/flowers, and refuse to buy and sell animals and plants protected. Students have also been able to provide their best photos based on the assessment of the trainers. Thus, students are expected to be able to convey the message of biodiversity conservation through their photographic works.

Senescence of T Lymphocytes: Implications for Enhancing Human Immunity

As humans live longer, a central concern is to find ways to maintain their health as they age. Immunity declines during ageing, as shown by the increased susceptibility to infection by both previously encountered and new pathogens and by the decreased efficacy of vaccination. It is therefore crucial to understand the mechanisms responsible for this decrease in immunity and to develop new strategies to enhance immune function in older humans. We discuss here how the induction of senescence alters leukocyte, and specifically T cell, function. An emerging concept is that senescence and nutrient sensing-signalling pathways within T cells converge to regulate functional responses, and the manipulation of these pathways may offer new ways to enhance immunity during ageing