Maximum Life Research Articles

Evolutionary analysis of the mTOR pathway provide insights into lifespan extension across mammals

BackgroundLifespan extension has independently evolved several times during mammalian evolution, leading to the emergence of a group of long-lived animals. Though mammalian/mechanistic target of rapamycin (mTOR) signaling pathway is shown as a central regulator of lifespan and aging, the underlying influence of mTOR pathway on the evolution of lifespan in mammals is not well understood.ResultsHere, we performed evolution analyses of 72 genes involved in the mTOR network across 48 mammals to explore the underlying mechanism of lifespan extension. We identified a total of 20 genes with significant evolution signals unique to long-lived species, including 12 positively selected genes, four convergent evolution genes, and five longevity associated genes whose evolution rate related to the maximum lifespan (MLS). Of these genes, four positively selected genes, two convergent evolution genes and one longevity-associated gene were involved in the autophagy response and aging-related diseases, while eight genes were known as cancer genes, indicating the long-lived species might have evolved effective regulation mechanisms of autophagy and cancer to extend lifespan.ConclusionOur study revealed genes with significant evolutionary signals unique to long-lived species, which provided new insight into the lifespan extension of mammals and might bring new strategies to extend human lifespan.

Study on the Influences of Adding Rare Earth Ce on the Precipitation Behaviors of TiN Inclusions in 20CrMnTi.

The morphologies and sizes of TiN inclusions in gear steel 20CrMnTi have a significant impact on its service performance. This paper selects rare earth Ce to modify TiN inclusions in 20CrMnTi. The inclusions are analyzed by SEM (scanning electron microscope), EBSD (electron back-scattered diffraction), EDS (energy disperse spectroscopy), and OTS statistical software, and Thermo-Calc software is used to calculate the inclusion formations. The inclusions of MgAlO4-Ce and CeAlO3 can be formed when rare earth Ce is added into 20CrMnTi, which becomes TiN nucleation core after precipitation. Without the addition of rare earth Ce, square TiN inclusions ranging from 2 to 5 μm account for 60% of the total inclusions in 20CrMnTi. After adding rare earth Ce, the TiN inclusions in 20CrMnTiCe account for 36.7% of the total inclusions. Due to the new phase formations of MgAlO4-TiN and CeAlO3-TiN with sizes less than 2 μm, the titanium-containing inclusions are refined. Fatigue tests are conducted on the steels before and after the addition of Ce. The average fatigue lives of 20CrMnTi do not reach 107 times, and the deviations between the maximum and minimum fatigue lives are great. Large-sized TiN are the main inclusions that affect the fatigue performance of 20CrMnTi. The average fatigue lives of 20CrMnTiCe exceed 107 times, and the deviations of the fatigue lives are smaller than those of 20CrMnTi.

DNA methylation networks underlying mammalian traits.

Using DNA methylation profiles (n = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in HOXL subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.

Experimental Study and 3D Optimization of Small-Scale Solar-Powered Radial Turbine Using 3D Printing Technology

Small-Scale Turbines (SSTs) are among the most important energy-extraction-enabling technologies in domestic power production systems. However, owing to centrifugal forces, the high rotating speed of SSTs causes excessive strains in the aerofoil portions of the turbine blades. In this paper, a structural performance analysis is provided by combining Finite Element Methods (FEM) with Computational Fluid Dynamics (CFD). The primary objective was to examine the mechanical stresses of a Small-Scale Radial Turbine (SSRT) constructed utilizing 3D printing technology and a novel plastic material, RGD 525, to construct a SSRT model experimentally. After introducing a suitable turbine aerodynamics model, the turbine assembly and related loads were translated to a structural model. Subsequently, a structural analysis was conducted under various loading situations to determine the influence of different rotational speed values and blade shapes on the stress distribution and displacement. Maximum von Mises and maximum main stresses are significantly affected by both the rotor rotational speed and the working fluid input temperature, according to the findings of this research. The maximum permitted deformation, on the other hand, was more influenced by rotational speed, while the maximum allowable fatigue life was more influenced by rotating speed and fluid intake temperature. Also, the region of the tip shroud in the rotor had greater deflection values of 21% of the blade tip width.

Assessment of Shelf life of Chrysanthemum (Dendranthema x grandiflora Tzelev.) var. Marigold Flowers as Influenced by Phenophase Based Irrigation and Nutrition Schedule

The present investigation was conducted in the Division of Flower and Medicinal Crops at the ICAR-Indian Institute of Horticultural Research, Bengaluru, to evaluate the influence of phenophase based irrigation and fertigation schedules on shelf life of chrysanthemum (Dendranthema x grandiflora Tzelev.) var. Marigold. The experiment comprised of three main plots (irrigation regimes) and five sub plots (nutrient regimes) and was laid out in split plot design with three replications. Irrigation regime at 0.8, 1.0 and 1.2 ER at vegetative, bud and flowering phases, respectively along with weekly fertigation of NPK @ 75:112.5:75 kg /ha (75% RDF) in three split doses of 40:20:20 % NPK during vegetative phase, 30:40:40 % NPK during bud phase and 30:40:40% NPK during flowering phase, recorded the maximum shelf life of flowers (12.15 days) whereas, the minimum shelf life (7.60 days) was observed in the irrigation regime at 0.6,0.8 and 1.0 ER at vegetative, bud and flowering phases, respectively along with conventional method soil application of recommended dose of fertilizer (100:150:100 Kg NPK/ha).The shelf life of flowers had significantly high positive association with the physiological parameters of the plant viz., relative water content (0.728), transpiration rate (0.201), single flower weight (0.559) and stomatal conductance rate (0.492). Whereas, the photosynthetic rate (0.214), diameter of the flower head (0.269) and estimated flower yield (0.047) were significantly and positively correlated with shelf life of flowers. However, the days taken for bud appearance (-0.250) was negatively associated with shelf life of flowers.

(Re-)Examining age and growth increments of the clam Venus verrucosa

Warty venus Venus verrucosa is a commercially important bivalve species that is widely distributed in the Mediterranean Sea. Understanding the main biological characteristics of exploited species, including their age and growth dynamics, are crucial for fisheries assessment, monitoring programmes and sustainable resource management. In this study, we analysed the age of the largest V. verrucosa specimens collected in Pag Bay, eastern Adriatic Sea, to investigate the maximal lifespan of this species. We used images of acetate peel replicas of the shell hinge region to visualize and count the growth increments. Radiocarbon content (14C) of selected shell material was analysed to corroborate the long lifespan derived from counting the growth lines in acetate peel replicas of etched shell sections. The maximum estimated lifespan of the analysed V. verrucosa specimens was 29 years, which is more than a decade longer than previously known. Pronounced variations in growth rates were noted among specimens of similar size, clearly indicating that shell size is not a reliable indicator of age for this species. Therefore, caution is advised when using the size-frequency distribution of the population to interpret the age structure of V. verrucosa.

Abstract P2002: Variability In The Relationship Between Heart Rate And Automatic Breathing Rate Throughout The Mouse Lifespan

Background: Autonomic neural surveillance maintains a symphonic relationship between heart and breathing rhythms. We have established how heart beat interval variability changes across mouse lifespan (6 months - 30 months) in the presence and absence of double autonomic blockade (Baltimore Longitudinal Study on Aging in Mice, BLSAM; Geroscience 2022, PMID: 35759167). Objective: To determine how the automatic breathing rate (BR) changes with age in the same BLSAM cohort, and whether the BR and Heart Rate (HR) track each other in the presence and absence of double autonomic blockade across the lifespan of individual mice. Methods: The BLSAM cohort consists of 58 mice in which HR and BR were assessed from the EKG (under light anesthesia) at 3-month intervals, beginning at 6 months of age until the end of life (30 months of age). EKG was recorded in the presence and absence double autonomic blockade (i.p injection of atropine, 0.5mg/kg, and propranolol, 1mg/kg). Data were analyzed via a mixed ANOVA. Results: The BR remained stable until approximately 21 months of age, and then became sharply reduced between 21 and 30 months of age (Fig. A). The pattern of HR change over the adult life span was similar to that of BR (Fig. B). Both HR and BR were significantly (p<0.05) reduced in the presence of double autonomic blockade (arrows in figs). The relative magnitude of BR reduction beyond 21 months of age was substantially greater than the relative reduction in HR over this age range, resulting in a marked increase in HR/BR Ratio (Fig. C), which was also significantly impacted by autonomic function. Conclusion: Thus, beginning at approximately the 70% of maximum mice lifespan, the harmony between heart rhythm and breathing rhythm gradually deteriorates.

Optimization of CNC Milling Parameters Based on Tool Life and Process Carbon Emission Prediction Models

Aiming at the problems of short tool life and high carbon emission in the process of CNC milling, a multi-objective optimization method of process parameters based on the BP neural network and NSGA-II algorithm is proposed. Based on the data sets generated by CNC milling under different process parameters, with tool life and process carbon emissions as outputs and different process parameter combinations as inputs, a BP neural network-based tool life and process carbon emissions prediction model is constructed. Taking the maximum tool life and minimum process carbon emission as the optimization goals, the NSGA-II process parameter multi-objective optimization main model is constructed. The model is then used as the objective function of the main model and optimized to obtain the Pareto optimal solution set. The optimal solution decision is made on the Pareto optimal solution set using the Topsis method, and the optimal process parameter combination is obtained. The optimization results show that the method can accurately predict the tool life and process carbon emission of CNC milling. It can also effectively optimize the process parameters, which provides a new method for the low-carbon optimization of CNC milling parameters.

FROM POPULATIONAL OBSERVATIONS TO AN ASSESSMENT OF THEIR STATE: EXPERIENCE FROM A COMPREHENSIVE STUDY ON THE DEMOGRAPHIC PARAMETERS OF THE WESTERN SIBERIAN POPULATION OF THE EUROPEAN PIED FLYCATCHER, <i>FICEDULA HYPOLEUCA</i> (MUSCICAPIDAE, PASSERIFORMES)

Key demographic parameters were calculated using the European pied flycatcher (Ficedula hypoleuca) as a model species for the study of bird population ecology. In the Tomsk Region, southeastern part of western Siberia, birds nesting in nest boxes situated in natural forests for 22 years were continuously studied. Where possible, life tables, probability models (CJS), and population matrix models were employed in the calculation of demographics. A comprehensive study of population characteristics made it possible to compare them with the results of other research and to demonstrate the degree of divergence in the estimation of demographic parameters obtained using different methods. On average, nestlings successfully left their nests in 87.6% of breeding attempts. The percentage of immigrants, residents, and autochthons in the static age distribution of females amounted to 41.7, 25.3, and 33.0%, respectively, vs 30.8, 25.3, and 43.9% in males, The maximum age for female autochthons was 7 years, compared to 8 years for male autochthons. Male residents lived to be x + 5 years old, while female residents lived to be x + 7 years old. Autochthonous males and females showed about the same local survival rates. These were the highest in yearlings (0.54) and gradually decreased with the age of individuals. The local survival rate of males of unknown origins is comparable to that of autochthonous males. Females of unknown origins had the lowest local survival rates. Birds could start nesting as young as one year old and as old as six years. Ringing revealed that 68.9% of males started breeding in their first year of life, compared to 59.9% of females that started in their first year. Only 39.2% of females and 46.3% of males among the birds that survived and returned to our control sites started breeding as yearlings, vs 66.9% of two-year-old females and 71.1% of males. The proportion of the birds that returned to their birth place amounted to 11.1%. Females produced 9.1 fledglings on average per lifetime, vs 9.6 fledglings for males. The minimum life expectancy for fledglings was 1.2–1.49 and 1.2–1.62 years, vs the maximum life expectancy for individuals that survived for one year, which was 1.94 and 1.96 years for males and females, respectively. For males and females, the generation time was 3.13–3.32 and 3.18–3.39 years, respectively. The sensitivity and elasticity analysis of the population growth rate based on the constructed projection matrix revealed that it was the survival rate of juvenile and sexually mature individuals between one and two years of age that primarily drove the population growth rate. Using the demographic data obtained for the species’ population in natural habitats in the Southeast of western Siberia and the population matrix model constructed on its basis, we believe it is possible to compare the state of populations inhabiting ecosystems, both unspoiled and disturbed (transformed), in various areas across the distribution range of the European pied flycatcher.

Effect of Sucrose and Aluminium Sulphate on Vase Life of Cut Chrysanthemum (Dendranthema grandiflora) cv. Fireside Cushion

The present investigation was laid out in Completely Randomized design (CRD) with 10 treatments and each replicated thrice. The treatment T7 ‘Sucrose 2% + Aluminium sulphate @ 200 ppm reported significantly better performance compared to other treatments, in terms of water uptake (6.79g/stem), flower diameter (6.00 cm), weight of spikes (42.50 g), spike length (11.50 cm), spike diameter (2.33 mm), total solution consumption (36.00 ml), vase life (15 days), gross returns (72 Rs/treatment) and net returns (27 Rs/treatment). The highest B:C ratio (1.80) was also found in the same treatment T7 i.e., Sucrose 2 % + Aluminium sulphate @ 200 ppm and also attained maximum vase life among the treatments.

The Evolution and Ecology of Oxidative and Antioxidant Status: A Comparative Approach in African Mole-Rats.

The naked mole-rat of the family Bathyergidae has been the showpiece for ageing research as they contradict the traditional understanding of the oxidative stress theory of ageing. Some other bathyergids also possess increased lifespans, but there has been a remarkable lack of comparison between species within the family Bathyergidae. This study set out to investigate how plasma oxidative markers (total oxidant status (TOS), total antioxidant capacity (TAC), and the oxidative stress index (OSI)) differ between five species and three subspecies of bathyergids, differing in their maximum lifespan potential (MLSP), resting metabolic rate, aridity index (AI), and sociality. We also investigated how oxidative markers may differ between captive and wild-caught mole-rats. Our results reveal that increased TOS, TAC, and OSI are associated with increased MLSP. This pattern is more prevalent in the social-living species than the solitary-living species. We also found that oxidative variables decreased with an increasing AI and that wild-caught individuals typically have higher antioxidants. We speculate that the correlation between higher oxidative markers and MLSP is due to the hypoxia-tolerance of the mole-rats investigated. Hormesis (the biphasic response to oxidative stress promoting protection) is a likely mechanism behind the increased oxidative markers observed and promotes longevity in some members of the Bathyergidae family.

Solar-assisted hybrid oil heating system for heavy refinery products storage

The purpose of this study is to investigate the potential use of solar energy within an oil refinery to reduce its fossil fuel consumption and greenhouse gas emissions. A validated ASPEN HYSYS model was used to investigate the products produced from heavy crude oil in the refinery. Using TRNSYS software, the proposed Parabolic Trough Collector (PTC)-based solar heating system paired with the boiler is modelled. Sensible thermal energy storage (TES) system is integrated into the refinery's process heating to handle the intermittent nature of solar energy. It was discovered that 463 m2 of the PTC area coupled with a 15000-L TES tank can result in a maximum life cycle cost savings of 21.046 thousand USD for an annual heat supply of 116,944 MWh to generate steam at a temperature of 200–220 °C. In the proposed hybrid heating system, the yearly solar fraction is determined to be 26.99% and the payback period is 8.77 years with the average solar irradiance of 900 W/m2. In addition, the system can yearly reduce greenhouse gas (GHG) emissions by about 34.045 tonnes of CO2 equivalents.

BASICS OF BIOLOGY OF AGING FOR MSU NON-BIOLOGISTS

The history of the creation of the course of lectures “Basics of the Biology of Aging” at the School of Biology of Lomonosov Moscow State University, as well as at the Department of Life Science and Engineering of Harbin Institute of Technology is brie y described. In the process of teaching this course, the author got the impression that its main provisions may also be of interest to students of non-biological specialties, who have recently been quite often involved in the work on the implementation of gerontological grants. This is largely determined, apparently, by the signi cantly increased funding for this kind of research in recent years. In turn, this is a consequence of the fact that the average life span of people in developed countries has increased dramatically over the past decades. However, the maximum life span has not changed much (it is now the same as it was thousands of years ago, it is just that the chances of living to the age of a centenarian have become much greater). If earlier people often died at an early age from various diseases not related to age (mainly infectious diseases), now, due to signi cant advances in medicine, most people live to old age. As a result, death “from aging” is becoming more common. At the same time, many people have a very vague idea of what aging is, what are its mechanisms and how to ght it. In this regard, in 2022, an interschool elective course of lectures was organized at MSU for students of any departments of the university, except for the School of Biology itself. It is called “Basics of the biology of aging, or everything you wanted to know about aging (but were afraid to ask).” The material of the lectures was specially adapted for students who are not biologists by their main specialty. The main emphasis in the course, consisting of 12 lectures, is made on the fundamental de nitions and methodical/methodological approaches used in gerontology. The article lists the questions submitted for the students’ test and brie y analyzes its results.

Long-Term Behavior of Nanoclay/TiO2 Nanoparticles Modified Carbon/Glass Fiber–Reinforced Hybrid Composites

Abstract Polymer composites are widely used as a primary structural material in lightweight construction industries due to their high strength-to-weight ratio and low cost. However, the mechanical properties get degraded when exposed to adverse environmental conditions. Hybridization of nanofillers and fibers can improve the hygroscopic behavior of polymer composites. In this work, the long-term performance of nanoclay/titanium dioxide–modified carbon/glass-reinforced hybrid composites under a seawater environment was investigated. The specimens were immersed in seawater (100 % relative humidity, 32°C) for 90 days. The effect of moisture absorption on the specimens was evaluated using water absorption, tensile, and flexural tests. Experimental results showed that the addition of nanofillers and carbon/glass hybridization had a significant impact on the water barrier properties and decay in mechanical properties. The residual life of the laminates under humid environmental conditions was predicted using an exponential function. Constituent materials and duration of exposure had a significant impact on the property’s degradation. The test findings showed that the (90°G/0°G/90°C)S sequenced laminate at 2 wt. % of nanofillers had a maximum residual life of 1,619 days under tensile loading and 3,051 days under flexural loading after 90 days of aging.

Evaluation of comparative parasitic efficiency and biology of hymenopteran egg parasitoids, Trichogramma chilonis and T. japonicum on Corcyra cephalonica and Helicoverpa armigera

Aim: To evaluate the comparative parasitic efficiency and biology of Trichogrammatid wasps on noble laboratory host Corcyra cephalonica as well as on Helicoverpa armigera, the cosmopolitan, polyphagous and precarious insect pest of many cultivated crops. Methodology: The biology of Trichogramma chilonis and T. japonicum, their sex ratio, and parasitic efficiency were studied. Host insects were reared on artificial diet to obtain their eggs for initiating the experiment. Egg-card pieces were prepared with the irradiated eggs of respective host insects. Egg-cards were introduced into the tubes containing freshly emerged adult parasitoids. Parasitized egg-cards (Trichocards) were kept separately in plastic tube to study the biological attributes and percent parasitization of the parasitoids. Egg cards of different host eggs taking eggs of different age groups were prepared to study the effect of age of host eggs on the biological efficiency of the parasitoids. Results: Irrespective of Trichogramma species, the duration (d) of eggs to adult period was more when reared on the eggs of H. armigera than on the eggs of C. cephalonica. Maximum life stage duration of T. chilonis and T. japonicum from egg to adult was 8.2 days and 10.2 days, respectively, when reared on H. armigera eggs. There was maximum parasitization (84.8%) of fresh eggs of C. cephalonica by T. chilonis as compared to the egg parasitization of 73.4% by T. japonicum. Likewise, extreme parasitization of fresh eggs of H. armigera was recorded as 62.4% when parasitized by T. chilonisas against 59.7% parasitization by T. japonicum. Interpretation: According to the study, H. armigera eggs have the finest biological and parasitic features in terms of the highest adult longevity, sex ratio, mean progeny female-1, and mean adult egg-1, making them the best for mass production of the egg parasitoids, T. chilonis. Key words: Corcyra cephalonica, Host eggs, Helicoverpa armigera, Parasitization, Trichogramma

Aging Rate Indicators: Speedometers for Aging Research in Mice.

A "biomarker of aging" is conceptualized as an index of how far an individual has moved along the path from youth to old age. In contrast, an aging rate indicator (ARI) represents a measure of speed, rather than distance, that is, a measure of how rapidly the individual is moving toward the phenotypic changes typical of old age. This essay presents and reviews recent data suggesting common characteristics of slow-aging mice, whether the slowed aging is caused by a mutant allele, the calorie restriction diet, or drugs that slow aging and extend mean and maximal lifespan. Some of the candidate ARIs, shared by nine varieties of slow-aging mice, are physiological changes seen in fat, fat-associated macrophages, muscle, liver, brain, and plasma. Others are molecular measurements, reflecting activity of mTORC1, selective mRNA translation, or each of six MAP kinases in two distinct MAPK cascades in liver, muscle, or kidney. Changes in ARIs are notable in young adult mice after 8 months of drug or diet exposure, are detectable in mutant mice at least as early as 4-6 months of age, and persist until at least 18-22 months. Many of the candidate ARIs are thought to play an influential role in cognition, inflammation, exercise responses, and control of metabolic rate, and are thus plausible as modulators of age-related physiological and neurological illnesses. In principle, screening for drugs that induce alterations in ARIs in normal young adult mice might facilitate the search for preventive medicines that can retard aging and late-life illnesses in mice or in human populations.

Low-Cycle Fatigue Behavior and Fracture Characteristics of Low-Cost Ti-2Fe-0.1B Alloy

In recent decades, the effect of Fe element addition on titanium alloy has been investigated extensively due to the development of low-cost titanium alloys, as well as B microalloying, which could decrease the grain size of titanium alloys during the casting process. As a key structural material, the study of the fatigue behavior of titanium alloys is crucial and always attractive for scientists. Hence, in this paper, the low cycle fatigue (LCF) behavior and fracture characteristics of a low-cost Ti-2Fe-0.1B alloy with a lamellar structure were investigated systematically, five different strain amplitudes (Δεt/2) in the range from 0.6% to 1.4% were selected to control the LCF process. It was found that the Ti-2Fe-0.1B alloy exhibits continuous cyclic softening behavior in the cycle as a whole at Δεt/2 ≤ 1.2%, while at Δεt/2 = 1.4%, it exhibits slight cyclic hardening at the initial stage of the cycle, then shows cyclic softening. Compared with pure titanium and other typical titanium alloys, the Ti-2Fe-0.1B alloy indicated maximum fatigue life under the same strain amplitude, it can be attributed to the fine grain size result from the effect of Fe element and trace B, which could hinder the dislocation movement and crack propagation.

Longevity toxicity after chronic α -endosulfan exposure in wild population of Drosophila melanogaster Oregon-R (Diptera: Drosophilidae)

The rapid increase in the world population causes different problems such as nutrition and shelter. In this case, people brutally destroy arable land to shelter, and concretization is rapidly spreading. In addition, it is necessary to increase the amount of products to be taken from the limited agricultural areas for the food needs of the increasing population. The decrease in agricultural areas appears as a factor that reduces the amount of product taken from the unit area. In addition, weeds and especially insects reduce the yield, storage, and marketing quality of products obtained from restricted areas. This type of plant products can also be considered a disease carrier vector in the food chain. To increase the yield, various insecticides have been developed against target organisms such as insects and one of these insecticides is α-endosulfan. However, non-target organisms living in the same ecosystem can also be affected by all these insecticides.
 In the present study, it was researched whether the chronic α-endosulfan application has an effect on longevity in non-target organisms. According to the data obtained, α-endosulfan shortened the maximum and mean lifespan in both male and female populations of the Oregon-R wild strain of Drosophila melanogaster based on dose-time interaction. The shortening observed in life span for both populations was statistically significant (p

Acarbose suppresses symptoms of mitochondrial disease in a mouse model of Leigh syndrome.

Mitochondrial diseases represent a spectrum of disorders caused by impaired mitochondrial function, ranging in severity from mortality during infancy to progressive adult-onset disease. Mitochondrial dysfunction is also recognized as a molecular hallmark of the biological ageing process. Rapamycin, a drug that increases lifespan and health during normative ageing, also increases survival and reduces neurological symptoms in a mouse model of the severe mitochondrial disease Leigh syndrome. The Ndufs4 knockout (Ndufs4-/-) mouse lacks the complex I subunit NDUFS4 and shows rapid onset and progression of neurodegeneration mimicking patients with Leigh syndrome. Here we show that another drug that extends lifespan and delays normative ageing in mice, acarbose, also suppresses symptoms of disease and improves survival of Ndufs4-/- mice. Unlike rapamycin, acarbose rescues disease phenotypes independently of inhibition of the mechanistic target of rapamycin. Furthermore, rapamycin and acarbose have additive effects in delaying neurological symptoms and increasing maximum lifespan in Ndufs4-/- mice. We find that acarbose remodels the intestinal microbiome and alters the production of short-chain fatty acids. Supplementation with tributyrin, a source of butyric acid, recapitulates some effects of acarbose on lifespan and disease progression, while depletion of the endogenous microbiome in Ndufs4-/- mice appears to fully recapitulate the effects of acarbose on healthspan and lifespan in these animals. To our knowledge, this study provides the first evidence that alteration of the gut microbiome plays a significant role in severe mitochondrial disease and provides further support for the model that biological ageing and severe mitochondrial disorders share underlying common mechanisms.

Gene expressions associated with longer lifespan and aging exhibit similarity in mammals.

Although molecular features underlying aging and species maximum lifespan (MLS) have been comprehensively studied by transcriptome analyses, the actual impact of transcriptome on aging and MLS remains elusive. Here, we found that transcriptional signatures that are associated with mammalian MLS exhibited significant similarity to those of aging. Moreover, transcriptional signatures of longer MLS and aging both exhibited significant similarity to that of longer-lived mouse strains, suggesting that gene expression patterns associated with species MLS contribute to extended lifespan even within a species and that aging-related gene expression changes overall represent adaptations that extend lifespan rather than deterioration. Finally, we found evidence of co-evolution of MLS and promoter sequences of MLS-associated genes, highlighting the evolutionary contribution of specific transcription factor binding motifs such as that of E2F1 in shaping MLS-associated gene expression signature. Our results highlight the importance of focusing on adaptive aspects of aging transcriptome and demonstrate that cross-species genomics can be a powerful approach for understanding adaptive aging transcriptome.