Why senescence is important

Leaf senescence. Annual Review of Plant Biology 58 , — Auxin response factor 2 ARF2 plays a major role in regulating auxin-mediated leaf longevity. Journal of Experimental Botany 61 , — Direct ubiquitination of pattern recognition receptor FLS2 attenuates plant innate immunity.

Science , — Quantitative trait loci analysis of leaf and plant longevity in Arabidopsis thaliana. Journal of Experimental Botany 57 , — High-throughput and computational study of leaf senescence through a phenomic approach. Frontiers in Plant Science 8 , Genetic variation suggests interaction between cold acclimation and metabolic regulation of leaf senescence.

Plant Molecular Biology 87 , — Mizukami Y , Fischer RL. Scientific Reports 6 , Identification of three genetic loci controlling leaf senescence in Arabidopsis thaliana.

The Plant Journal 12 , — The Plant Journal 43 , 29 — Circadian rhythms from flies to human. Modelling transcriptional networks in leaf senescence. NAC transcription factors in senescence: from molecular structure to function in crops. Plants 4 , — Powell AE , Lenhard M. Control of organ size in plants. Current Biology 22 , R — R The Plant Cell 27 , — A transcriptome-wide study on the microRNA- and the Argonaute 1-enriched small RNA-mediated regulatory networks involved in plant leaf senescence.

Plant Biology 18 , — EIN3 and ORE1 accelerate degreening during ethylene-mediated leaf senescence by directly activating chlorophyll catabolic genes in Arabidopsis. PLoS Genetics 11 , e Identification of a novel E3 ubiquitin ligase that is required for suppression of premature senescence in Arabidopsis.

The Plant Journal 59 , 39 — The cytokinin response factors modulate root and shoot growth and promote leaf senescence in Arabidopsis. The Plant Journal 85 , — Phytochrome A and Phytochrome B have overlapping but distinct functions in Arabidopsis development. Arabidopsis cytokinin receptor mutants reveal functions in shoot growth, leaf senescence, seed size, germination, root development, and cytokinin metabolism.

The Plant Cell 18 , 40 — Rougvie AE. Control of developmental timing in animals. Nature Reviews. Genetics 2 , — Nature Communications 5 , Sarvepalli K , Nath U. Hyper-activation of the TCP4 transcription factor in Arabidopsis thaliana accelerates multiple aspects of plant maturation.

The Plant Journal 67 , — The Plant Journal 68 , — Schippers JH. Transcriptional networks in leaf senescence. Current Opinion in Plant Biology 27 , 77 — Control of jasmonate biosynthesis and senescence by miR targets. PLoS Biology 6 , e AraPheno: a public database for Arabidopsis thaliana phenotypes. Nucleic Acids Research 45 , D — D The Plant Cell 24 , — Control of Arabidopsis apical—basal embryo polarity by antagonistic transcription factors. Molecular Plant 7 , — The Plant Journal 71 , — Novel allelic variants in ACD6 cause hybrid necrosis in local collection of Arabidopsis thaliana.

The Genomes Consortium. Thomas H , Stoddart JL. Annual Review of Plant Physiology 31 , 83 — Natural allelic variation underlying a major fitness trade-off in Arabidopsis thaliana. Activation of the Arabidopsis thaliana immune system by combinations of common ACD6 alleles. PLoS Genetics 10 , e Circadian activity rhythms and mortality: the study of osteoporotic fractures.

Journal of the American Geriatrics Society 58 , — Early senescence and cell death in Arabidopsis saul1 mutants involves the PAD4 -dependent salicylic acid pathway. Comprehensive dissection of spatiotemporal metabolic shifts in primary, secondary, and lipid metabolism during developmental senescence in Arabidopsis. Sugars, senescence, and ageing in plants and heterotrophic organisms. Journal of Experimental Botany 60 , — ORE9, an F-box protein that regulates leaf senescence in Arabidopsis.

The Plant Cell 13 , — Plant leaf senescence and death — regulation by multiple layers of control and implications for aging in general. Journal of Cell Science , — Programming of plant leaf senescence with temporal and inter-organellar coordination of transcriptome in Arabidopsis. The Arabidopsis homolog of human minor spliceosomal protein UK plays a crucial role in U12 intron splicing and plant development.

Time zones: a comparative genetics of circadian clocks. Nature Reviews Genetics 2 , — Disrupting the circadian clock: gene-specific effects on aging, cancer, and other phenotypes. Aging 3 , — JAZ7 negatively regulates dark-induced leaf senescence in Arabidopsis.

Mitogen-activated protein kinase 6 mediates nuclear translocation of ORE3 to promote ORE9 gene expression in methyl jasmonate-induced leaf senescence. Journal of Experimental Botany 67 , 83 — Plant Science , 57 — Journal of Experimental Botany 66 , — The Plant Journal 84 , — Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.

Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Multi-layered regulation of leaf senescence. Newly emerging regulatory mechanisms of leaf senescence. Senescence programs and fitness.

Conclusions and future challenges. New insights into the regulation of leaf senescence in Arabidopsis. These results suggest that PhHD-Zip plays an important role in regulating petunia flower senescence. Moreover, a transcriptome study reported that several genes involved in ABA biosynthesis, catabolism, and signaling pathways were induced by exogenous cytokinins BA treatment Trivellini et al. In the experiment reported by Chang et al.

These results suggest that in addition to the ethylene pathway, the cytokinins seem to be strongly involved in the regulation of ABA biosynthesis and its degradation in flower tissues, thus ABA plays a primary role in petunia flower senescence.

The fruit is the development of the ovary after the fertilization and protects the seeds until complete maturation. The seeds represent the germ plasm of the plants and are responsible for the dissemination of the species. From an ecological point of view, fruits during the unripe stage represent an organ that must be protected from insects or frugivores.

A fruit must be unattractive and its green color allows the camouflage itself with leaves. The ripening of fruits is a unique coordination of various biochemical and developmental pathways regulated by ethylene, which affects color, texture, nutritional quality and aroma of fruits Barry and Giovannoni, During ripening in climacteric fruits, the ethylene regulates firmness and color changes involving chlorophyll reduction, increase in carotenoids or anthocyanins, sugars, and biosynthesis of volatile organic compounds VOCs.

Ethylene is tightly correlated with the VOCs biosynthesis, which increases in ripe fruit and enhances the attraction of frugivores. The inhibition of ethylene biosynthesis reduces production of VOCs and reduces the aroma of fruits Figure 2. It has been found that transgenic apples expressing antisense genes for ACS or ACO produced lower VOCs and in particular, the strongest reduction was observed in the esters, which were 3—4 fold lower compared with WT Dandekar et al.

The exogenous application of ethylene reconverted the VOCs evolution. This result indicates that ethylene inhibits the key steps of volatile biosynthesis. The study with the application of 1-MCP or AVG demonstrated that ethylene regulates VOCs biosynthesis directly through the pathway of volatile biosynthesis and indirectly through the ethylene perception. In fact, apricots Prunus armeniaca treated with ethylene biosynthesis inhibitor, such as AVG, strongly reduced the VOCs biosynthesis, while the 1-MCP, an ethylene action inhibitor, enhanced the evolution of aldehydes Valdes et al.

A Schematic and simplified ethylene and VOCs biosynthesis during fruit development. VOCs biosynthesis derive from different pathways such as phenylpropanoids, fatty acid, and carotenoids degradation. B The main enzymes involved in cell wall degradation during fruit ripening and senescence. The action of these enzymes induces loss of firmness and softening. In climacteric fruits, ethylene biosynthesis increases and shows a peak corresponding to respiration pattern, while in non-climacteric fruits the ethylene declines with fruit ripening and senescence.

The tomato has been used as a model plant for studying the role of ethylene in fruit ripening. The transition from unripe to ripe fruit induces several biochemical changes that involve ethylene biosynthesis and perception. Unripe fruits produce a low amount of ethylene and are insensitive to exogenous ethylene. Hence, ethylene treatments do not induce the fruit ripening system 1. At the beginning of ripening, ethylene production increases and induces an increase of autocatalytic biosynthesis.

These fruits, in this development stage, if exposed to exogenous ethylene show a burst of ethylene production and ripen faster system 2.

Fruits are classified in system 1 when they produce a low amount of ethylene and tissues are insensitive to exogenous ethylene Alexander and Grierson, The delay of ethylene increase is the most common strategy used in post-harvest for prolonging the storage and increasing the shelf life.

The inhibition of ethylene biosynthesis or action usually leads to an extension of shelf life of the climacteric fruits. Ethylene regulates fruit ripening by affecting the ACS and ACO genes and the fruit specific polygalacturonase, involved in the depolymerization of cell wall pectin during ripening Smith et al. It affects pectin methylesterase PME , which provides accessibility to pectin by polygalacturonase and phytoene synthase responsible for the pigmentation of many fruits and flowers Koch and Nevins, ; Fray and Grierson, Cloned mRNAs that accumulate in the unripe tomato fruits exposed to exogenous ethylene were investigated through blot hybridization experiment.

The expression of cloned genes was developmentally regulated by the ethylene during fruit ripening, with more mRNAs produced by these genes in ripe fruits than in unripe fruits and the increase in mRNA was repressed by norbornadiene, an ethylene action inhibitor Lincoln et al. Gene expression analysis of Never-ripe Nr and additional tomato receptor homologs indicated that Nr and LeETR4 transcripts were most abundant in the ripen fruit tissues Zhou et al. Alba et al.

The mutation of the ethylene receptor Nr , which reduces ethylene sensitivity and inhibits ripening, also influenced fruit morphology, seed number, ascorbate accumulation, carotenoid biosynthesis, ethylene evolution, and the expression of many genes during fruit maturation, indicating that ethylene governed multiple aspects of development both prior and during fruit ripening in tomato Alba et al. In tomato, the E8 gene plays a role in the negative regulation of ethylene biosynthesis through repression of ethylene signal transduction.

The expression of the gene increased during ripening and its antisense repression resulted in an increased ethylene evolution but delayed ripening Penarrubia et al. The relationship between ethylene and auxin in the fruit development has been studied.

Auxins are involved in fruit development and inhibit ripening Brady, The exogenous application of auxins in different fruits delayed the senescence such as observed in Bartlett pears Pyrus communis ; Frenkel and Dyck, , banana Musa acuminate ; Purgatto et al.

The application of auxin lowered the ethylene production in sliced apples Malus domestica , if applied at pre-climacteric phase, while enhancing its biosynthesis at the climacteric stage Lieberman et al. There exists a crosstalk between auxin and ethylene; and Bleecker and Kende pointed out that auxins can stimulate the biosynthesis of more climacteric ethylene through its inductive action on the expression of the key enzyme ACS Abel and Theologis, Ethylene and auxins are tightly related during fruit senescence.

The free auxin increases during senescence and stimulates ethylene biosynthesis. Further studies are required to understand the ethylene sensitivity changes after 1-MCP treatment.

The nature and transcriptional response of CTG led to discovering a rise in free auxin in the 1-MCP treated fruits. The exogenous application of cytokinins or compounds with cytokinins-like activity increased the sugar content of fruits and induced earlier ripening. Recent studies have shown that CPPU delayed the ethylene increase during fruit ripening and also delayed central placenta softening Ainalidou et al.

In avocado, the application of isopentenyl adenosine increased the ethylene and fruit ripening Bower and Cutting, The studies regarding the role of cytokinins in the plant senescence are available in the literature, but the relationship between cytokinins and ethylene during fruit ripening and senescence has not yet completely been elucidated and needs further investigations.

In tomato fruit, ABA biosynthesis occurs via carotenoids degradation pathways and the key enzyme is the 9- cis -epoxycarotenoid dioxygenase NCED. The ABA content increases following the biosynthesis of carotenoids during ripening. These changes are associated with ripening and also with ethylene production. The exogenous application of ABA increases ethylene biosynthesis Mou et al.

These results suggest that ABA can be a trigger for ethylene production and influence fruit ripening Zhang et al. In banana fruit, ABA stimulates ripening independently from the ethylene. ABA application increases all hydrolases, which can enhance the softening, with exception to the polygalacturonase activity Lohani et al. Interestingly, these authors provide new insights into the regulatory mechanism underlying tomato fruit development and ripening with the ethylene involved in the downstream signal transduction of ABA and sucrose, as a negative regulator of ASR gene expression, which influenced the expression of several cell wall and ripening-related genes leading to fruit softening.

The relationship of other phytohormones such as ABA and GA with ethylene during fruit senescence needs to be elucidated. The loss of firmness or softening of fruits is a very important quality parameter.

The softening is due to cell wall degradation induced from several enzymes that are synergistically activated. Almost all these enzymes are encoded by multi-genes family, which regulates the spatial-temporal activation of these enzymes. Ethylene plays a crucial role in regulating these genes and enzymes during ripening and senescence. The cell wall degradation is facilitated by expansins that are proteins, which are involved in the enlargement of cell matrix. This phenomenon occurs during cell wall growth and disruption.

The action of these enzymes has been found to be tightly associated with the fruit ripening and senescence Civello et al. The expansins are tightly dependent on pH. The transcription of these enzymes is carried out by gene families, which have been isolated and characterized in several plant species. Different isoforms can provide the expansins action during plant growth and fruit senescence, linking the development stage with the activation of specific isoforms. The inhibition of ethylene biosynthesis also reduced and inhibited the EXP1 gene expression Rose et al.

The activation of the expansin EXP1 has also been shown in other climacteric fruits such as banana Trivedi and Nath, Pectin methylesterase is an enzyme activated before fruit ripening and catalyzes the de-esterification of pectin, by removing the methyl group C-6 of galacturonic acid and allows the polygalacturonase action.

The PME has an important role during fruit senescence and cell wall degradation with loss of firmness. This enzyme is stimulated by ethylene and inhibited by ethylene inhibitors such as 1-MCP El-Sharkawy et al.

This enzyme is activated after the action of PME and is also induced by ethylene. In antisense ACC synthase tomato, the exposure to ethylene rapidly increased transcript accumulation of the PG. The gene expression of PG was directly correlated with ethylene concentrations used Sitrit and Bennett, Bananas treated with ethylene increased the activity of this enzyme, while the use of 1-MCP reduced its activity Lohani et al.

Analogous results were observed in mango treated with ethylene for inducing ripening or treated with 1-MCP for delaying ripening Chourasia et al. The cell wall degrading enzymes is sequentially activated during ripening and senescence.

Ethylene is one key regulator of these enzymes at transcriptional and post-transcriptional level Figures 2A,B. It may be summarized that ethylene plays a key role in plant growth and development. The action of ethylene in the growth and development may not be isolated. It triggers the network of signaling pathways and influences through the interaction with other phytohormones regulation of several processes.

The understanding of the crosstalk between ethylene and other phytohormones in regulating growth and senescence could provide a promising strategy to manipulate the content of these hormones through molecular techniques in order to get specific plant responses.

During plant life, the transition from vegetative to reproductive stages and senescence is largely influenced by ethylene and its interplay with other plant hormones.

This networking not only influences the ethylene concentration but also tissues sensitivity. There are few studies focusing on the molecular changes in plant tissues after the combined treatments of ethylene with other plant hormones. These studies should be extended to different organs and development stages to deeply understand the intricate network affecting relevant agronomic traits such as yield, longevity, and appearance morphology.

The discovery of new synergistic or antagonist relationships among ethylene and other hormones can have great potential to support cell division and differentiation processes during plant development, to enhance crop yield by delaying aging and prolong shelf-life of flowers and maintain the quality of climacteric fruits. Moreover, the equilibrium between the ethylene biosynthesis and its perception influences the crop adaptability and performance under different stress conditions.

It has been shown that other plant hormones can positively or negatively influence this equilibrium. The interplay of ethylene and plant hormones on plant performance should also be investigated at the post-translation level.

NI and MK wrote on the role of ethylene in leaf, flower and fruit growth and development and its interaction with other hormones in the process, together with the introduction. NK suggested the concept of the manuscript, wrote the abstract and looked over the whole manuscript order and language and contributed to the overall look of the manuscript. AFe, AT, and AFr wrote on the role of ethylene in leaf, flower and fruit senescence and its interaction with other hormones in the process.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer BVDP and handling Editor declared their shared affiliation, and the handling Editor states that the process nevertheless met the standards of a fair and objective review. Abel, S. Early genes and auxin action. Plant Physiol. Abeles, F. Ethylene in Plant Biology , 2nd Edn. Google Scholar.

Achard, P. The plant stress hormone ethylene controls floral transition via DELLA-dependent regulation of floral meristem-identity genes. Integration of plant responses to environmentally activated phytohormonal signals. Science , 91— Plant Cell 15, Adamczyk, B. Plant J. Aharoni, N. Ethylene as a regulator of senescence in tobacco leaf discs. Aida, R.

Extension of flower longevity in transgenic torenia plants incorporating ACC oxidase transgene. Plant Sci. Ainalidou, A. Integrated analysis of metabolites and proteins reveal aspects of the tissue-specific function of synthetic cytokinin in kiwifruit development and ripening.

Alba, R. Transcriptome and selected metabolite analyses reveal multiple points of ethylene control during tomato fruit development. Plant Cell 17, — Alexander, L. Ethylene biosynthesis and action in tomato: a model for climacteric fruit ripening. An, F. Plant Cell 22, — Anderson, L. Effects of abscisic acid on growth and leaf development in american pondweed Potamogeton nodosus POIR. Bar, M. Leaf development and morphogenesis. Development , — Barry, C.

Ethylene and fruit ripening. Plant Growth Regul. Bauchot, A. Effect of aminocyclopropanecarboxylic acid oxidase antisense gene on the formation of volatile esters in Cantaloupe Charentais melon cv. Food Chem. Belimov, A. Rhizosphere bacteria containing 1-aminocyclopropanecarboxylate deaminase increase yield of plants grown in drying soil via both local and systemic hormone signalling. New Phytol. Beyer, E. A potent inhibitor of ethylene action in plants. Binder, B.

The copper transporter RAN1 is essential for biogenesis of ethylene receptors in Arabidopsis. Bleecker, A. The ethylene-receptor family from Arabidopsis: structure and function.

B , — Insensitivity to ethylene conferred by a dominant mutation in Arabidopsis thaliana. Science , — Ethylene: a gaseous signal molecule in plants. Cell Dev. Bower, J. Avocado fruit development and ripening physiology. Brady, C. Fruit ripening. Breitel, D. PLoS Genet. Brown, K. Ethylene and abscission.

Buchanan-Wollaston, V. The molecular biology of leaf senescence. The molecular analysis of leaf senescence - a genomics approach. Plant Biotechnol. Burg, S. Ethylene, plant senescence and abscission. Auxin-induced ethylene formation: its relation to flowering in the pineapple.

Science , Calderini, O. Delay of leaf senescence in Medicago sativa transformed with the ipt gene controlled by the senescence-specific promoter SAG Plant Cell Rep.

Carabelli, M. Canopy shade causes a rapid and transient arrest in leaf development through auxin-induced cytokinin oxidase activity.

Genes Dev. Chang, H. Overproduction of cytokinins in petunia flowers transformed with P-SAG IPT delays corolla senescence and decreases sensitivity to ethylene. Chang, X. A petunia homeodomain-leucine zipper protein, PhHD-Zip, Plays an important role in flower senescence.

Chen, L. Transformation of broccoli Brassica oleracea var. Chen, M. Chen, W. Cheng, Y. Auxin synthesized by the YUCCA flavin monooxygenases is essential for embryogenesis and leaf formation in Arabidopsis. Plant Cell 19, — Chourasia, A. Differential expression of pectate lyase during ethylene-induced postharvest softening of mango Mangifera indica var. Civello, P. An expansin gene expressed in ripening strawberry fruit.

Dandekar, A. Effect of down-regulation of ethylene biosynthesis on fruit flavor complex in apple fruit. De Grauwe, L. Novel mechanisms of ethylene-gibberellin crosstalk revealed by the gai eto double mutant.

Plant Signal. De Martinis, D. Silencing gene expression of the ethylene-forming enzyme results in a reversible inhibition of ovule development in transgenic tobacco plants. Plant Cell 11, — Dong, C. Dubois, M. Dugardeyn, J. To grow or not to grow: what can we learn on ethylene-gibberellin cross-talk by in silico gene expression analysis? Eda, M. This is a result of damage occurring in repair-resistant regions of the genome known as DNA segments with chromatin alterations reinforcing senescence, such as telomeres Rodier et al.

Given the key roles of p53, additional regulatory layers exist. Recently, the interaction between Forkhead box protein O4 FOXO4 and p53 has been shown to play an important role in modulating p53 localization and transcriptional activity during senescence Baar et al. Interestingly FOXO transcription factors regulate aging, with FOXO activity in Drosophila melanogaster leading to delayed aging in response to disrupted protein homeostasis and oxidative stress Demontis and Perrimon, Given this unusual concentration of three tumor suppressors in barely 35 kb, this locus plays a key regulatory role and is frequently mutated in cancer Gil and Peters, ; Kim and Sharpless, However, most of these are found in noncoding regions, and the precise mechanism of action is unclear.

In particular, p16 INK4a is considered an aging biomarker. With exceptions such as during senescence-induced during development , p16 INK4a is also one of the best markers of senescence. An analysis of the pathways regulating p16 INK4a shows coincidences with those controlling development. This has been argued to formulate the theory that aging might be driven by gradual functional decay of developmental pathways Martin et al. Besides growth arrest, the production of a complex mixture of secreted factors, termed the SASP or senescence-messaging secretome, is the most relevant phenotypic program implemented in senescent cells.

The specific combination of secreted factors is thought to depend on the cell type and the senescent inducer. However, many of the key effectors of the SASP and its regulatory mechanism seemed to be shared. DNA damage Rodier et al. There are additional layers of SASP regulation. There is also a global remodeling of enhancers in senescent cells, and the recruitment of BRD4 to superenhancers adjacent to SASP genes is needed for their induction Tasdemir et al.

The SASP is responsible for many of the positive and negative functions attributed to senescent cells Fig. One of the major functions of the SASP is to recruit the immune system to eliminate senescent cells. In general terms, the effects are positive. During tumor initiation, SASP-mediated immune recruitment acts as an extrinsic tumor suppressor mechanism Xue et al. In contrast, SASP-mediated recruitment of immature myeloid cells has immune suppressive effects on prostate and liver cancer Di Mitri et al.

In addition, the SASP can stimulate tumorigenesis by promoting angiogenesis e. Specific components of the SASP have other physiological functions, such as contributing to fibrotic tissue remodeling, whereby matrix metalloproteinases MMPs contribute to degrade fibrotic plaques in the ECM that may be beneficial in the context of liver fibrosis and wound healing Krizhanovsky et al.

Recently, it has been postulated that senescent cells accumulating in response to tissue damage can also promote stemness and reprogramming Ritschka et al. However, how this fits with the increased number of senescent cells but decreased stemness potential observed during aging is unclear. On the other hand, factors secreted by senescent cells can reinforce the senescent phenotype, potentially exacerbating senescence during aging.

Moreover, senescent cells can also induce a so-called paracrine senescence response Acosta et al. This autocrine reinforcement or paracrine transmission of senescence could potentially explain some of the detrimental effects of aberrant accumulation of senescent cells during aging. During aging, the SASP is thought to be partially responsible for persistent chronic inflammation, also known as inflammaging, that contributes to multiple age-related phenotypes.

This contribution of SASP in inflammaging is beginning to be investigated using senolytic models. The direct elimination of senescent cells in aged kidney Baker et al. It would be pertinent in future aging therapies to understand how specific aspects of the SASP contribute to the deterioration or protection of tissues.

Although the contribution of senescence to aging has been long suspected, only recently has the connection been confirmed. This has been made possible by the use of molecular biomarkers of senescence and the establishment of novel genetic models to study the role of senescent cells in vivo. Furthermore, p16 INK4a accumulates during aging.

Its knockout also mitigates functional decline and proliferative exhaustion upon HSC transplantation Janzen et al. The possible detrimental effects cause by p16 INK4a overexpression may be outweighed by their clear tumor suppressive benefits, with a threefold reduction in tumor incidence Matheu et al.

One of the biggest hindrances to investigating senescence in vivo has been the lack of robust, consistent markers. However, these may yield mixed results. The use of additional senescence markers, such as lipofuscin, which accumulates in the cytoplasm of senescent cells, could be applied to bridge this gap Sharpless and Sherr, Another useful tool that has emerged is the use of bioluminescent senescence reporters.

With the advent of p16 INK4a -LUC mice expressing a luciferase reporter under the control of a p16 INK4a promoter, there is now confirmation that multiple tissues show an exponential age-related increase in p16 INK4a expression that correlates with higher levels of proinflammatory factors or SASP components Yamakoshi et al.

Establishing causality of a gene in diseases such as cancer is usually a matter of generating appropriate knockout or overexpression mouse models. Seminal studies by Baker et al. The elimination of senescent cells improved several age-associated conditions, delayed tumor formation, and ameliorated the side effects of chemotherapy Baker et al. These studies have finally confirmed that senescence causes, or at least contributes to, aging.

There is clear evidence suggesting how the SASP participates in the clearance of premalignant cells or contributes to tumor progression Kang et al. The detrimental role for chronic inflammation during aging is further supported by clinical data Libby, ; Brunt et al.

Aging phenotypes such as frailty Soysal et al. The increased levels of chronic inflammation in these instances are collectively termed inflammaging Franceschi and Campisi, The reason for such increases in levels of proinflammatory molecules remains unknown.

Although accumulated damage and lifelong antigenic load may undoubtedly contribute to this increase in inflammation, senescence may also help mediate inflammaging.

This contribution of senescence to inflammaging may be via several coalescing effects, the first being through the SASP. As damage accumulates in tissues, the number of senescent cells and their SASP also increases. This process is usually resolved by clearance of the senescent cells by the immune system Kang et al.

In aged individuals, however, senescence also contributes to a decline in immune function termed immunosenescence, thereby compromising the clearance of senescent cells and exacerbating inflammation. Emerging studies using genetic systems or drugs ablating senescent cells suggest that the elimination of senescent cells reduces inflammation across tissues Baker et al.

Future studies will need to establish the causal link between the SASP, chronic inflammation, and tissue dysfunction. These might require the generation of novel mouse models that take advantage of our knowledge on SASP regulation. Now that a general causative role for senescence during aging has been established, the next step is to identify how senescence contributes to different age-related pathologies such as glaucoma Liton et al.

Thanks to the use of senolytic drugs and genetic models for senescence ablation, we are progressing quickly in that task. Senescence is a strong tumor suppressor mechanism that limits cancer initiation through both cell-intrinsic Collado and Serrano, and cell-extrinsic mechanisms Kang et al.

Senescent cells can contribute to tumor progression by enhancing the proliferative potential of cancer cells Krtolica et al. Therefore, the increased numbers of senescent cells present in aged tissues could contribute to the increased incidence of cancer with age. Supporting this, a delayed onset in tumor formation is observed when senescent cells are eliminated Baker et al.

Senolytic therapy also reduces the incidence of metastasis, the leading cause of cancer-related deaths Demaria et al. Aged individuals often display a reduced glomerular filtration rate and cortical volume that can result in glomerulosclerosis and nephron atrophy, both of which are associated with increased expression of p16 INK4a and p53 Melk et al.

Senescence has detrimental effects in most renal diseases analyzed Sturmlechner et al. Ablation of senescent cells protects against glomerulosclerosis and improves kidney function in aged mice Baker et al. One of the largest risk factors for the development of type 2 diabetes is age. Fibrosis is a pathological condition whereby tissue accumulates ECM proteins such as collagen, resulting in tissue scarification, usually in response to damage. Senescence appears to have both beneficial and detrimental roles during fibrosis and wound healing.

The detrimental nature of senescence in IPF was recently demonstrated using senolytics. Elimination of senescent fibroblasts in a mouse model of lung fibrosis reduced expression of profibrotic SASP components and improved pulmonary function Schafer et al. Cirrhosis is the pathological outcome from liver fibrosis and nonalcoholic fatty liver disease, which in turn is a result of hepatic steatosis, the abnormal accumulation of lipids in hepatocytes Pellicoro et al.

Senescence is associated with liver fibrosis Kim et al. The risk of developing nonalcoholic fatty liver disease increases with age Hardy et al. Rice transcription factor OsMYB delays leaf senescence by down-regulating abscisic acid accumulation and signaling.

Deferral of leaf senescence with calcium. Characterization of senescence-associated protease activities involved in the efficient protein remobilization during leaf senescence of winter oilseed rape. Plant Sci. In vivo participation of red chlorophyll catabolite reductase in chlorophyll breakdown. Chlorophyll breakdown: Pheophorbide a oxygenase is a Rieske-type iron-sulfur protein, encoded by the accelerated cell death 1 gene.

Chlorophyll breakdown in senescent Arabidopsis leaves. Characterization of chlorophyll catabolites and of chlorophyll catabolic enzymes involved in the degreening reaction. Regulated expression of an isopentenyltransferase gene IPT in peanut significantly improves drought tolerance and increases yield under field conditions.

A transcriptome-wide study on the microRNA- and the Argonaute 1-enriched small RNA-mediated regulatory networks involved in plant leaf senescence. Plant Biol. EIN3 and ORE1 accelerate degreening during ethylene-mediated leaf senescence by directly activating chlorophyll catabolic genes in Arabidopsis. PLoS Genet. Diverse range of gene activity during Arabidopsis thaliana leaf senescence includes pathogen-independent induction of defense-related genes.

Maize expressing the sunflower transcription factor HaHB11 has improved productivity in controlled and field conditions. Identification of a novel chloroplast protein AtNYE1 regulating chlorophyll degradation during leaf senescence in Arabidopsis. Reverse genetic identification of CRN1 and its distinctive role in chlorophyll degradation in Arabidopsis. J Integr Plant Biol. Delayed leaf senescence induces extreme drought tolerance in a flowering plant. Robatzek S, Somssich IE.

Senescence-associated proteases in plants. Physiol Plant. Stress-induced senescence and plant tolerance to abiotic stress. Sakakibara H. Cytokinins: activity, biosynthesis, and translocation. Multilayered regulation of membrane-bound ONAC is essential for abscisic acid-induced leaf senescence in rice. Rice ONAC inhibits leaf senescence and increases salt tolerance and tiller angle. The plant circadian clock: from a simple timekeeper to a complex developmental manager.

Cold Spring Harb Perspect Biol. Light perception: a matter of time. Mg-dechelation of chlorophyll a by Stay-Green activates chlorophyll b degradation through expressing non-yellow coloring 1 in Arabidopsis thaliana. Pheophytin pheophorbide hydrolase pheophytinase is involved in chlorophyll breakdown during leaf senescence in Arabidopsis. Control of jasmonate biosynthesis and senescence by miR targets. PLoS Biol. Schreiber A, Peter M. Substrate recognition in selective autophagy and the ubiquitin—proteasome system.

Highly oxidized peroxisomes are selectively degraded via autophagy in Arabidopsis. Shiloh Y, Ziv Y. The ATM protein kinase: regulating the cellular response to genotoxic stress, and more. Nat Rev Mol Cell Biol. Natural variations at the Stay-Green gene promoter control lifespan and yield in rice cultivars.

Shu K, Yang W. E3 ubiquitin ligases: ubiquitous actors in plant development and abiotic stress responses. Cytokinin biochemistry in relation to leaf senescence. Endogenous cytokinin levels and exogenous applications of cytokinins in relation to sequential leaf senescence of tobacco.

Onge K, Chen J, et al. Senescence-induced ectopic expression of the A. Association of BrERF72 with methyl jasmonate-induced leaf senescence of Chinese flowering cabbage through activating JA biosynthesis-related genes. Hortic Res. Thomas H, Ougham H. The stay-green trait. Altered membrane lipase expression delays leaf senescence. Biochem Soc Trans. Tollenaar M.

Physiological basis of genetic improvement of maize hybrids in Ontario from to Crop Sci. Molecular mechanisms of DNA damage and repair: progress in plants. Crit Rev Biochem Mol Biol. A NAC gene regulating senescence improves grain protein, zinc, and iron content in wheat. Ueda H, Kusaba M. Strigolactone regulates leaf senescence in concert with ethylene in Arabidopsis.

Ueda M, Seki M. Histone modifications form epigenetic regulatory networks to regulate abiotic stress response. Transcription analysis of Arabidopsis membrane transporters and hormone pathways during developmental and induced leaf senescence.

Van Wijk KJ. Protein maturation and proteolysis in plant plastids, mitochondria, and peroxisomes. In: Merchant SS, editor. Annual review of plant biology, vol. HvPap-1 C1A protease actively participates in barley proteolysis mediated by abiotic stresses.

Vierstra RD. The ubiquitin—26S proteasome system at the nexus of plant biology. Vijg J. Somatic mutations and aging: a re-evaluation. Mutat Res. Early senescence and cell death in Arabidopsis saul1 mutants involve the PAD4-dependent salicylic acid pathway. Fitness analyses of Arabidopsis thaliana mutants depleted of FtsH metalloproteases and characterization of three FtsH6 deletion mutants exposed to high light stress, senescence and chilling.

The role and regulation of autophagy and the proteasome during aging and senescence in plants. Identification and fine mapping of a stay-green gene Brnye1 in pakchoi Brassica campestris L. Theor Appl Genet. Defect in Brnym1, a magnesium-dechelatase protein, causes a stay-green phenotype in an EMS-mutagenized Chinese cabbage Brassica campestris L.

Wang SH, Blumwald E. Stress-induced chloroplast degradation in Arabidopsis is regulated via a process independent of autophagy and senescence-associated vacuoles. The H3K27me3 demethylase REF6 promotes leaf senescence through directly activating major senescence regulatory and functional genes in Arabidopsis. WRKY55 transcription factor positively regulates leaf senescence and the defense response by modulating the transcription of genes implicated in the biosynthesis of reactive oxygen species and salicylic acid in Arabidopsis.

Autophagy contributes to leaf starch degradation. Wasternack C. Jasmonates: an update on biosynthesis, signal transduction and action in plant stress response, growth and development.

Ann Bot. The plant PTM viewer, a central resource for exploring plant protein modifications. Spatial patterns and metabolic regulation of photosynthetic parameters during leaf senescence. ORE9, an F-box protein that regulates leaf senescence in Arabidopsis. Extended leaf longevity in the ore-1 mutant of Arabidopsis with a reduced expression of a plastid ribosomal protein gene.

Leaf senescence: systems and dynamics aspects. Plant leaf senescence and death - regulation by multiple layers of control and implications for aging in general.

J Cell Sci. Programming of plant leaf senescence with temporal and inter-organellar coordination of transcriptome in Arabidopsis. Ubiquitin facilitates a quality-control pathway that removes damaged chloroplasts. Plant nt siRNAs mediate translational repression and stress adaptation. Regulation of leaf senescence and crop genetic mprovement. Transcription factor CDF4 promotes leaf senescence and floral organ abscission by regulating abscisic acid and reactive oxygen species pathways in Arabidopsis.

EMBO Rep. The Arabidopsis homolog of human minor spliceosomal protein UK plays a crucial role in U12 intron splicing and plant development. Genome-wide analysis of microRNAs and their target genes related to leaf senescence of rice. Enhancing cytokinin synthesis by overexpressing ipt alleviated drought inhibition of root growth through activating ROS-scavenging systems in Agrostis stolonifera.

Proteomic changes associated with expression of a gene ipt controlling cytokinin synthesis for improving heat tolerance in a perennial grass species. Strigolactone signaling regulates rice leaf senescence in response to a phosphate deficiency. Yamada Y, Umehara M. Possible roles of strigolactones during leaf senescence.

Yamaguchi S. Gibberellin metabolism and its regulation. Rice tillering dwarf mutant dwarf3 has increased leaf longevity during darkness-induced senescence or hydrogen peroxide-induced cell death. Genes Genet Syst. Activation of autophagy by unfolded proteins duringendoplasmic reticulum stress.

Yang Y, Guo Y. Unraveling salt stress signaling in plants. The transcription factor ZmNAC accelerates leaf senescence downstream of the ethylene signalling pathway in maize. Up-regulation of autophagy by low concentration of salicylic acid delays methyl jasmonate-induced leaf senescence.

Involvement of an ethylene response factor in chlorophyll degradation during citrus fruit degreening. Beyond the genetic code in leaf senescence. Autophagy negatively regulates cell death by controlling NPR1-dependent salicylic acid signaling during senescence and the innate immune response in Arabidopsis.

Senescence of aerial parts is impeded by exogenous gibberellic acid in herbaceous perennial Paris polyphylla. AtFtsH6 is involved in the degradation of the light-harvesting complex II during high-light acclimation and senescence. Plant Cell Rep. Eur J Cell Biol. Identification and characterization of a novel stay-green QTL that increases yield in maize. Zhang K, Gan SS. Salicylic acid 3-hydroxylase regulates Arabidopsis leaf longevity by mediating salicylic acid catabolism.

An ABA-regulated and Golgi-localized protein phosphatase controls water loss during leaf senescence in Arabidopsis. Senescence-inducible expression of isopentenyl transferase extends leaf life, increases drought stress resistance and alters cytokinin metabolism in cassava. The Arabidopsis mitochondrial protease FtSH4 is involved in leaf senescence via regulation of WRKY-dependent salicylic acid accumulation and signaling.

Chlorophyll degradation: the tocopherol biosynthesis-related phytol hydrolase in Arabidopsis seeds is still missing. Genetic network between leaf senescence and plant immunity: crucial regulatory nodes and new insights.

Circadian evening complex represses Jasmonate-induced leaf senescence in Arabidopsis. Overexpression of a NAC transcription factor delays leaf senescence and increases grain nitrogen concentration in wheat.

WRKY22 transcription factor mediates dark-induced leaf senescence in Arabidopsis. Mol Cells. Zhu JK. Abiotic stress signaling and responses in plants. Overexpression of salt-induced protein salT delays leaf senescence in rice. Genet Mol Biol. Chloroplast degradation: multiple routes into the vacuole. Cytokinin response factor 6 represses cytokinin-associated genes during oxidative stress. Cytokinin inhibition of leaf senescence.

Plant Signal Behav. Download references. We apologize to our colleagues whose research works are not properly reviewed here because of space limitation. You can also search for this author in PubMed Google Scholar.

All authors read and approved the final manuscript. Correspondence to Ying Miao or Hongwei Guo. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material.

If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Reprints and Permissions. Guo, Y. Leaf senescence: progression, regulation, and application. Mol Horticulture 1, 5 Download citation. Received : 09 February Accepted : 11 March Published : 16 June Anyone you share the following link with will be able to read this content:.