ARTICLE | doi:10.20944/preprints202309.2114.v1
Subject: Biology And Life Sciences, Aging Keywords: Human; lifespan; aging; consciousness; brain; integration
Online: 30 September 2023 (17:55:59 CEST)
Human longevity is an important but difficult goal due to the extreme complication of human body. If people could repeatedly transfer their consciousness from old bodies to new ones, their lifespan might be prolonged extremely. However, there are several difficulties which prevent the achievement of such a technique. In this paper, we propose an approach that can transfer human consciousness indirectly, and avoid or significantly relieve those difficulties. The strategy of our approach is to integrate the consciousnesses of two bodies (old and new) into a unique consciousness. By doing so, the consciousness is extended to the new body. After that, the consciousness shrinks and remains in the new body when the old body dies. This may also apply to integrating more than two bodies of human, or animal, or even across different species. After investigating thousands of literatures, we find quite strong evidence (related discoveries and technologies) that can support the proposed approach and its advantages. Beside prolonging human lifespan, the approach could also have other meaningful applications.
ARTICLE | doi:10.20944/preprints202309.1569.v1
Subject: Biology And Life Sciences, Aging Keywords: longevity; healthspan; lifespan; nutraceuticals; C. elegans
Online: 22 September 2023 (11:43:17 CEST)
Aging is a complex process associated with tissue degeneration and an increased risk of age-related diseases. This study aimed to evaluate the impact of Terasen®, a nutraceutical containing standardized extracts of Euterpe oleracea, Myrciaria dubia, and purified oil of Bixa orellana and Astrocaryum aculeatum on the lifespan of Caenorhabditis elegans, a widely used model organism for aging research. The findings demonstrated that Terasen® exhibited significant antioxidant activity and influenced the feeding behavior of C. elegans, leading to a reduced pharyngeal pumping rate and a decreased number of offspring produced by treated individuals. Notably, Terasen® also displayed a remarkable ability to extend the lifespan of C. elegans. These findings suggest that Terasen® may possess promising anti-aging effects in vivo, warranting further investigation.
REVIEW | doi:10.20944/preprints202308.1851.v1
Subject: Biology And Life Sciences, Aging Keywords: aging theories; gerontology; genetics; lifespan; evolvability; ageing
Online: 28 August 2023 (10:01:19 CEST)
Programmed aging refers to the idea that mammals (and some other multiparous sexually reproducing organisms) evolved complex biological mechanisms that cause gradually increasing fitness deterioration and internally limit individual organism lifetimes. The rationale is that this process enhances the survival (non-extinction) of a species population. Evolvability theories propose that mammals have evolved design characteristics that aid their ability to evolve, that is, reduce the time required for a particular increment of evolutionary adaptation and/or increase the precision with which the adaptation can be performed. Because an increase in evolvability aids a population in escaping extinction, evolution selects the associated design characteristics. Both of these concepts conflict with traditional (Darwinian) theory regarding the nature of evolution. However, more recent genetics discoveries have exposed rich detail regarding the nature of the evolution process including the fact that biological inheritance involves the transmission of organism design information from parent to descendant in digital form. These discoveries have acted to support both programmed aging and evolvability theories. Acquisition traits are those that depend for their evolutionary (fitness) value on the acquisition of something that gradually accumulates during an organism’s life but is not transmitted genetically to descendants. This situation causes these traits including language, immunity, intelligence, and social status to represent a special need for evolvability and programmed aging.
ARTICLE | doi:10.20944/preprints202308.1556.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: patient’s preferences; quality of life; lifespan; gender
Online: 22 August 2023 (10:22:49 CEST)
In view of the increasing age of cardiac surgery patients, questions arise about the expected postoperative quality of life and the hoped-for prolonged life expectancy. Little is known so far about this weighting by the patients concerned. This study aims to obtain information on the patient’s preferences. Between 2015 and 2017, data from 1349 consecutive patients from seven heart centers in Germany undergoing cardiac surgery were analyzed. Baseline data regarding the patient’s situation as well as a questionnaire regrading quality of life versus lifespan were taken preoperatively. Patients were divided by age into 4 groups: below 60, 60-70, 70-80, and above 80 years. As a result, if one had to decide between quality of life and length of life, about 60% of the male patients decided for quality of life, independent of their age. On the other hand, female patient’s decision for quality of life increased significantly with age, from 51% in the group below sixty to 76% in the group above eighty years. This finding suggests that the female patients adapt their preferences with age whereas male patients do not. This should impact further treatment decisions of elderly patients in cardiac surgery within a shared decision-making process.
REVIEW | doi:10.20944/preprints202307.1278.v1
Subject: Biology And Life Sciences, Aging Keywords: evolution, evolvability, biology, gerontology, lifespan, senescence, genetics
Online: 19 July 2023 (04:18:37 CEST)
As recently as 2002 programmed aging in mammals was widely thought to be theoretically impossible based on generally accepted concepts regarding the evolution process. However, as described in this article, genetics discoveries, results of selective breeding, and other direct evidence strongly support the idea that aging creates an evolutionary advantage and that therefore complex biological mechanisms evolved that control mammal aging. Like similar life-cycle programs that control reproduction, growth, and menopause the aging program can adjust the aging trait during an individual’s life to compensate for temporary or local changes in external conditions that alter the optimum lifespan for a particular species population. In addition, genetics discoveries strongly support the evolvability concept to the effect that sexually reproducing species can evolve design features that increase their ability to evolve, and that aging is one such feature.
ARTICLE | doi:10.20944/preprints202212.0326.v1
Subject: Biology And Life Sciences, Aging Keywords: C. elegans; drug; infection; lifespan; liposome; methodology
Online: 19 December 2022 (06:47:56 CET)
Liposome-mediated delivery is a possible means to overcome several shortcomings with C. elegans as a model for identifying and testing drugs that retard aging. These include interactions between drugs and the nematodes’ bacterial food source, and failure of drugs to be taken up into nematode tissues. To explore this, we have tested liposome-mediated delivery of a range of fluorescent dyes and drugs in C. elegans. Liposome encapsulation led to enhanced effects on lifespan, using smaller quantities of compound, and enhanced uptake of three dyes into the gut lumen. However, one dye (Texas red) did not cross into nematode tissues, indicating that liposomes cannot ensure uptake of any compound. Of six compounds previously reported to extend lifespan (vitamin C, N-acetylcysteine, glutathione (GSH), trimethadione, thioflavin T (ThT) and rapamycin), this effect was reproduced for the latter four in a condition-dependent manner. For GSH and ThT, antibiotics abrogated life extension, implying a bacterially-mediated effect. With GSH, this was attributable to reduced early death from pharyngeal infection, and associated with alterations of mitochondrial morphology in a manner suggesting a possible innate immune training effect. By contrast, ThT exhibited antibiotic effects. For rapamycin, significant increases in lifespan were only seen when bacterial proliferation was prevented. These results document the utility and limitations of liposome-mediated drug delivery for C. elegans. They also show how nematode-bacteria interactions can determine the effects of compounds on C. elegans lifespan in a variety of ways.
REVIEW | doi:10.20944/preprints202102.0491.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: mTORC1; mTORC2; rapamycin; rapalog; aging; lifespan; longevity
Online: 22 February 2021 (15:34:25 CET)
Inhibition of mTORC1 (mechanistic Target Of Rapamycin Complex 1) signaling promotes health and longevity in diverse model organisms. Over the past decade, excitement has built over the possibility that treatment with the mTORC1 inhibitor rapamycin can be utilized to treat or prevent age-related disease in humans. However, concerns over the side effects of rapamycin on immunity and metabolism have precluded the routine use of rapamycin as a geroprotective therapy. Here, we discuss the evidence that these negative side effects of rapamycin are largely mediated by off-target inhibition of a second mTOR Complex (mTORC2). Further, we discuss how intermittent treatment with rapamycin, specific dietary regimens, and new molecules may provide routes to the safer and more selective inhibition of mTORC1. We conclude that the time is ripe for the development of therapies based on the safe and selective inhibition of mTORC1 for the treatment or prevention of diseases of aging.
ARTICLE | doi:10.20944/preprints202101.0262.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: lifespan; aging; radioresistance; ionizing radiation; Agronaute; Piwi; Drosophila melanogaster
Online: 14 January 2021 (08:07:44 CET)
Small RNAs are essential for the coordination of many cellular processes, including the regulation of gene expression patterns, the prevention of genomic instability, and the suppression of mutagenic transposon activity. These processes determine aging, longevity, and sensitivity of cells and an organism to stress factors (particularly, ionizing radiation). The biogenesis and activity of small RNAs are provided by proteins of the Argonaute family. These proteins participate in the processing of small RNA precursors and the formation of an RNA-induced silencing complex. However, the role of Argonaute proteins in the regulation of lifespan and radioresistance remains poorly explored. We studied the effect of knockdown of Argonaute genes (AGO1, AGO2, AGO3, piwi) in various tissues on the Drosophila melanogaster lifespan and survival after the γ-irradiation at a dose of 700 Gy. In most cases, these parameters were reduced or did not change significantly in flies with tissue-specific RNA interference. Surprisingly, piwi knockdown in both the fat body and the nervous system caused a lifespan increase. But changes in radioresistance depended on the tissue in which the gene was knocked out. In addition, analysis of changes in retrotransposon levels and expression of stress response genes allowed us to determine associated molecular mechanisms.
ARTICLE | doi:10.20944/preprints202305.2036.v1
Subject: Environmental And Earth Sciences, Pollution Keywords: Multi-generation; Net Reproductive Rate (R0); Hatching delay; lifespan; acetylcholinesterase
Online: 30 May 2023 (04:20:02 CEST)
Two monophyletic Daphnia species (Daphnia magna and D. similis) were exposed to a sub-lethal concentration of Pb (50 µg/L) for nine generations under two food regimes (usual and restricted) and analysed for acetylcholinesterase (AChE) activity, hatching delay and lifespan, and Net Reproductive Rate (R0) at subcellular, individual and population levels, respectively. At the sixth generation, Pb acclimated neonates were moved to a clean media for three more generations to check for recovery. D. magna showed no Pb effect on Net Reproductive Rate (R0). However, Pb stimulated reproduction, reduced lifespan and decreased AChE activity. Hatching delay and lifespan did not improve during the recovery process, indicating genetic adaptation. Food restriction reduced R0, lifespan, delayed hatching, and increased AChE activity; opposite outcomes were shown for D. similis. Full recovery shown by R0 suggests a physiological acclimation of D. similis. Under food restriction, the animals exhibited a reduction of R0 and lifespan, delayed hatching and increased AChE activity; however, with no Pb effect. The recovery process under food restriction showed that D. similis might not cope with Pb exposure, indicating failed recovery. Such outcomes indicate that a model species' sensitivity may not represent another's sensitivity.
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: nitric oxide; nitrates; dietary potassium nitrate; Drosophila melanogaster; longevity; lifespan
Online: 29 January 2021 (14:20:31 CET)
The recently defined and yet rather new topic of Healthy aging is gathering more attention on the global stage. With world’s population getting older - it is rapidly becoming very important to develop and maintain functional abilities in older age and develop mechanisms to protect senior population from chronic diseases. One of the most effective components, as well as, one may call - process involved in, and strongly associated with aging is recently discovered and Nobel prize awarded - nitric oxide as a signaling molecule, which followed by later discoveries showed to have a positive metabolic, immune and anti-inflammatory effects. One of the most debated topics of the last decade in the scientific community is nitrates, one of the pathways involved in nitric oxide production. Thus, the objective of this study was to evaluate effect of different potassium nitrate concentrate supplementation on Drosophila melanogaster longevity. 0,5-3% potassium nitrate medium was analyzed on the life span and motor function in different groups consisting of 100 females fruit flies each. In this assay, female fly species supplemented with potassium nitrate diet showed life span increase by 18.6% and 5.1% with 1% and 2% KNO3- respectively with a positive impact on locomotor function. In conclusion, we found that low concentration of potassium nitrate medium increased lifespan and locomotor function in Drosophila melanogaster.
ARTICLE | doi:10.20944/preprints201908.0063.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: matreotype; proteomics; transcriptomics; lifespan; extracellular matrix; ECM; collagen; MMP; homeostasis
Online: 5 August 2019 (14:22:17 CEST)
Accumulation of damage is generally considered the cause of aging. Interventions that delay aging mobilize mechanisms that protect and repair cellular components. Consequently, research has been focused on studying the protective and homeostatic mechanisms within cells. However, in humans and other multicellular organisms, cells are surrounded by extracellular matrices (ECM), which are important for tissue structure, function and intercellular communication. During aging, components of the ECM become damaged through fragmentation, glycation, crosslinking, and accumulation of protein aggregation, all of which contribute to age-related pathologies. Interestingly, placing senescent cells into a young ECM rejuvenates them and we found that many longevity-assurances pathways re-activate de-novosynthesis of ECM proteins during aging. This raises the question of what constitutes a young ECM to reverse aging or maintain health? In order to make inroads to answering this question, I suggest a systems-level approach of quantifying the matrisome or ECM compositions reflecting health, pathology, or phenotype and propose a novel term, the “matreotype”, to describe this. The matreotype is defined as the composition and modification of ECM or matrisome proteins associated with or caused by a phenotype, such as longevity, or a distinct and acute physiological state, as observed during aging or disease. Every cell type produces its unique ECM. Interestingly, cancer-cell types can even be identified based on their unique ECM composition. Thus, the matreotype reflects cellular identity and physiological status. Defined matreotypes could be used as biomarkers or prognostic factors for disease or health status during aging with potential relevance for personalized medicine. Treatment with biologics that alter ECM-to-cell mechanotransduction might be a strategy to reverse age-associated pathologies. An understanding of how to reverse from an old to a young matreotype might point towards novel strategies to rejuvenate cells and help maintain tissue homeostasis to promote health during aging.
COMMUNICATION | doi:10.20944/preprints202301.0334.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: serotonin; pcpa; cystamine; dinophilida; invertebate models; aging; maternal serotonin; lifespan longevity
Online: 18 January 2023 (10:22:43 CET)
Serotonin (5-HT) is crucial molecule in animal kingdom. It is involved in control of multiple processes. It might act via transmembrane receptors or via postranslational protein modification (serotonylation). D. gyrociliatus is a marine worm-like invertebrate with quite short lifespan. In this study lifetime experiments were performed. We incubated freshly laid eggs, adult females lifelong in HTP, PCPA and cystamine. Every week we monitored the survived individuals. This was lifelong (about 5 moth) monitoring. The survival analysis demonstrated that PCPA and cystamine reduce lifespan longevity drastically and even in F1 offsprings from mothers with reduced level of serotonin. HTP incubation to the contary extended mean lifespan longevity up to 22 % even in F1 offsprings from mothers with extended levels of serotonin. Thus, our results demonstrated that serotonin impacts lifespan longevity and moreover the level of serotonin in mother organism affects offspring lifespan longevity.
ARTICLE | doi:10.20944/preprints202103.0205.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Niemann-Pick type C; soluble epoxide hydrolase; autophagy; cognitive decline; lifespan; inflammation; cholesterol; sphingolipids
Online: 5 March 2021 (21:48:31 CET)
Niemann-Pick type C (NPC) disease is a childhood autosomal recessive inherited rare neuro-degenerative disease, characterized by the accumulation of cholesterol and glycosphingolipids, implicating the autophagy-lysosome system. Inhibition of soluble epoxide hydrolase (sEH), an enzyme that metabolizes epoxy fatty acids (EpFAs) to 1,2-diols, exerts beneficial effects in mod-ulating inflammation and autophagy, critical features of the NPC disease. This study aimed to evaluate the effects of UB-EV-52 a sEH inhibitor (sEHi) in the Npc mouse model by administering for 4 weeks (5 mg/kg/day). Behavioral and cognitive assays (open field test (OF), elevated plus maze (EPM), novel object recognition test (NORT) and object location test (OLT) demonstrated that treatment produced an improvement in short- and long-term memory as well as in spatial memory. Moreover, the treatment with UB-EV-52 increased body weight and the lifespan by 25% and re-duced gene expression of the inflammatory markers (i.e. Il-1β and Mcp1) and improved oxidative stress (OS) markers (iNOS and Hmox1) in the treated Npc mice group. Regarding the autophagic markers, we surprisingly found significantly reduced levels of the ratio LC3B-II/LC3B-I and a significant reduction of brain protein levels of lysosomal-associated membrane protein-1 (LAMP-1) in Npc mice treated group compared to non-treated. Lipid profile analysis showed a significant reduction in lipid storage in the liver and some slight changes in brain tissue in treated Npc mice compared to non-treated groups. Thus, Our results suggest that the pharmacological inhibition of sEH ameliorates most of NPC’s characteristic traits in mice, demonstrating that sEH can be considered a potential therapeutic target for this condition.
REVIEW | doi:10.20944/preprints202305.1128.v1
Subject: Biology And Life Sciences, Aging Keywords: Polyamine; Spermine; Spermidine; Lifespan extension; Polyamine-rich food; age-related disease; Inflammation; Gene methylation; LFA-1
Online: 16 May 2023 (08:39:53 CEST)
The human polyamines spermine and spermidine are essential for cell function, and their properties have been extensively studied. However, research results of experiments conducted without understanding the properties of polyamines have been evaluated and published by reviewers who appear to have little knowledge of the properties of polyamines. It is sad that some studies repeat what was done more than half a century ago before polyamines were characterized. First, I explain the basic properties of polyamines that researchers need to know. Then, the relationship between changes in polyamine levels in the body and age- and lifestyle-related diseases is discussed. In addition, the epigenetic mechanism of action of polyamines in relation to healthy longevity and, conversely, age- and lifestyle-related diseases and the progression of senescence are discussed. Spermine, which increases with a polyamine-rich diet, acts to suppress aberrant gene methylation and proinflammatory status associated with aging. Meanwhile, chronic inflammation associated with aging induces the enzyme activity of spermine oxidase, which breaks down spermine and produces acrolein, resulting in reduced spermine levels. Acrolein, a toxic aldehyde that increases with age- and lifestyle-related diseases, is thought to accelerate these diseases.
REVIEW | doi:10.20944/preprints202103.0571.v3
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: diet; calorie restriction; ketosis; fasting; health span; lifespan; metabolic syndrome; insulin resistance; chronic non-communicable diseases; low-calorie; low-carb
Online: 12 April 2021 (13:06:01 CEST)
As Chronic Non-Communicable Diseases (CNCD) increase, preventive approaches become more crucial. In this review, Calorie Restriction (CR) effects on human beings were evaluated, comparing benefits and risks of different CR diets: classic CR vs ketosis-inducing diets, including Intermittent Fasting (IF), Classic Ketogenic Diet (CKD), Fasting Mimicking Diet (FMD), Very-Low-Calorie Ketogenic Diet (VLCKD) and Spanish Ketogenic Mediterranean Diet (SKMD). Special emphasis on Insulin Resistance (IR) was placed, as it mediates Metabolic Syndrome (MS), a risk factor for CNCD, and predicts MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.
REVIEW | doi:10.20944/preprints202306.0228.v2
Subject: Engineering, Electrical And Electronic Engineering Keywords: Prognostics; Ageing; Lithium-Ion Batteries; EV Batteries; Degradation; Electric vehicles; Failure; Solid Electrolyte Interphase; Lifespan Estimation; Battery Performance; Diagnostics; Lifetime Prediction
Online: 21 November 2023 (13:16:44 CET)
Lithium-ion batteries with improved energy densities have made understanding the Solid Electrolyte Interphase (SEI) generation mechanisms that cause mechanical, thermal, and chemical failures more complicated. SEI processes reduce battery capacity and power. Thus, a review of this area's understanding is important. It is essential to know how batteries degrade in EVs to estimate battery lifespan as it goes, predict, and minimize losses, and determine the ideal time for a replacement. Lithium-ion batteries used in EVs mainly suffer two types of degradation: calendar degradation and cycling degradation. Despite the existence of several existing works in the literature, several aspects of battery degradation remain unclear or have not been analyzed in detail. This work presents a systematic review of existing works in the literature. The results of the present investigation provide insight into the complex relationships among various factors affecting battery degradation mechanisms. Specifically, this systematic review examined the effects of time, side reactions, temperature fluctuations, high charge/discharge rates, depth of discharge, mechanical stress, thermal stress, and the voltage relationship on battery performance and longevity. The results revealed that these factors interact in complex ways to influence the degradation mechanisms of batteries. For example, high charge currents and deep discharges were found to accelerate degradation, while low temperatures and moderate discharge depths were shown to be beneficial for battery longevity. Additionally, the results showed that the relationship between cell voltage and State-of-Charge (SOC) plays a critical role in determining the rate of degradation. Overall, these findings have important implications for the design and operation of battery systems, as they highlight the need to carefully manage a range of factors to maximize battery performance and longevity. The result is an analysis of the main articles published in this field in recent years. This work aims to present new knowledge about fault detection, diagnosis, and management of lithium-ion batteries based on battery degradation concepts. The new knowledge is presented and discussed in a structured and comprehensive way.
REVIEW | doi:10.20944/preprints201811.0179.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: calorie restriction mimetics; anti-aging; lifespan extension; glucose metabolism modulation; chitosan; acarbose; SGLT2 inhibitor; 2-deoxy-D-glucose; D-allulose; D-glucosamine
Online: 7 November 2018 (15:26:42 CET)
Calorie restriction (CR) has been shown to prolong the lifespan of humans, but enforcing long-term CR is difficult. Therefore, a compound that reproduces the effect of CR without CR is needed. In this review, we summarize the current knowledge on compounds with CR mimetic (CRM) effects. More than 10 compounds have been listed as CRMs, some of which are conventionally categorized as upstream-type CRMs showing glycolytic inhibition while the others are categorized as downstream-type CRMs that regulate or genetically modulate intracellular signaling proteins. Among these, we focus on upstream-type CRMs and propose their classification as compounds with energy metabolism inhibition effects, particularly glucose metabolism modulation effects. The upstream-type CRMs reviewed include chitosan, acarbose, sodium-glucose cotransporter 2 inhibitors, and hexose analogs such as 2-deoxy-D-glucose, D-glucosamine, and D-allulose, which show anti-aging and longevity effects. Finally, we discuss the molecular definition of upstream-type CRMs.
ARTICLE | doi:10.20944/preprints202310.1134.v1
Subject: Engineering, Electrical And Electronic Engineering Keywords: carbon footprint; performance ratio; photovoltaic array system; PVsyst software; panel orienta-tion; levelized cost of electricity/energy (LCOE); payback period; return on investment (ROI); cost-effectiveness; project lifespan
Online: 18 October 2023 (08:12:42 CEST)
This study addresses the pressing energy constraints in nations like Bangladesh by proposing the implementation of photovoltaic (PV) microgrids. Given concerns about environmental degrada-tion, limited fossil fuel reserves, and volatile product costs, renewable energy sources are gaining momentum globally. Our research focuses on a grid-connected solar PV system model at Char Jazira, Lalpur, Natore, Rajshahi, Bangladesh. Through PVsyst simulation software, we assess the performance ratio (PR) and system losses, revealing an annual solar energy potential of 3375 MWh at Standard Test Condition (STC) efficiency. After considering losses, the system generates 2815 MWh annually, with 2774 MWh exported to the grid. We analyze an average PR of 78.63% and calculate a levelized cost of energy (LCOE) of 2.82 BDT/kWh [1 USD = 110 BDT]. The financial assessment indicates a cost-effective LCOE for the grid-connected PV system, with an annual gross income of 27744 BDT from selling energy to the grid and operating costs of 64060.60 BDT/year. Remarkably, this initiative can prevent 33074.061 tCO2 emissions over the project’s 25-year lifespan.