Integrating cellular senescence with the concept of damage accumulation in aging: Relevance for clearance of senescent cells

Understanding the aging process and ways to manipulate it is of major importance for biology and medicine. Among the many aging theories advanced over the years, the concept most consistent with experimental evidence posits the buildup of numerous forms of molecular damage as a foundation of the aging process. Here, we discuss that this concept integrates well with recent findings on cellular senescence, offering a novel view on the role of senescence in aging and age‐related disease. Cellular senescence has a well‐established role in cellular aging, but its impact on the rate of organismal aging is less defined. One of the most prominent features of cellular senescence is its association with macromolecular damage. The relationship between cell senescence and damage concerns both damage as a molecular signal of senescence induction and accelerated accumulation of damage in senescent cells. We describe the origin, regulatory mechanisms, and relevance of various damage forms in senescent cells. This view on senescent cells as carriers and inducers of damage puts new light on senescence, considering it as a significant contributor to the rise in organismal damage. Applying these ideas, we critically examine current evidence for a role of cellular senescence in aging and age‐related diseases. We also discuss the differential impact of longevity interventions on senescence burden and other types of age‐related damage. Finally, we propose a model on the role of aging‐related damage accumulation and the rate of aging observed upon senescent cell clearance.     

The migration of mitochondrial DNA fragments to the nucleus affects the chronological aging process of Saccharomyces cerevisiae

Migration of fragmented mitochondrial DNA (mtDNA) to the nucleus has been shown to occur in multiple species including yeast, plants, and mammals. Several human diseases, including Pallister–Hall syndrome and mucolipidosis, can be initiated by mtDNA insertion mutagenesis of nuclear DNA. In yeast, we demonstrated that the rate of mtDNA fragments translocating to the nucleus increases during chronological aging. The yeast chronological lifespan (CLS) is determined by the survival of nondividing cell populations. Whereas yeast strains with elevated migration rates of mtDNA fragments to the nucleus showed accelerated chronological aging, strains with decreased mtDNA transfer rates to the nucleus exhibited an extended CLS. Although one of the most popular theories of aging is the free radical theory, migration of mtDNA fragments to the nucleus may also contribute to the chronological aging process by possibly increasing nuclear genomic instability in cells with advanced age.     

Age‐related AMP‐activated protein kinase alterations: From cellular energetics to longevity

5’ adenosine monophosphate‐activated protein kinase (AMPK) is a key regulator of energy in the cell, which allows the cell/organism to survive with deficit of ATP. Since AMPK is involved in the adaptation to caloric restriction, the role of age‐related changes in AMPK activity in both the aging organism and the aging cell is actively investigated in gerontology. Studies on yeast, worms, flies, rodents, and primates have demonstrated an important effect of this regulator on key signalling pathways involved in the aging process. In some cases, researchers conclude that AMPK promotes aging. However, in our opinion, in such cases, we observe a disturbance in the adaptive ability because of the prolonged cell/organism presence in stressful conditions because the functional capacity of any adaptation system is limited. Interestingly, AMPK can regulate metabolic processes in noncell‐autonomous manner. The main effects of AMPK activation in the cell are realized in restriction of proliferation and launching autophagy. In tissues of an aging organism, the ability of AMPK to respond to energy deficit decreases; this fact is especially critical for organs that contain postmitotic cells. In this review, we have tried to consider the involvement of AMPK in age‐related changes in the cell and in the organism.     

南亚热带不同演替阶段森林优势树种叶片构建成本与机械抗性的协同关系

为探究不同演替阶段森林优势种叶片资源获取策略的差异以及叶片构建成本与机械抗性的关系,对我国南亚热带不同演替阶段森林14优势种的叶片构建成本、机械抗性、角质层厚度和比叶重等结构性状进行测定。结果表明,与演替早期相比,演替晚期优势种具有更高的单位面积叶片构建成本、叶片撕裂力以及穿透力,但其叶片最大光合速率较低;同时,单位面积叶片构建成本与机械抗性呈显著正相关关系,而叶片角质层厚度、比叶重等结构性状也与叶片构建成本、机械抗性均呈显著正相关。因此,从叶片能量投资策略上反映了南亚热带森林演替进程中叶片构建成本与机械抗性的协同关系。     

The collaborative study on the genetics of alcoholism: Sample and clinical data

The collaborative study on the genetics of alcoholism (COGA) is a multi-site, multidisciplinary project with the goal of identifying how genes are involved in alcohol use disorder and related outcomes, and characterizing how genetic risk unfolds across development and in conjunction with the environment and brain function. COGA is a multi-generational family-based study in which probands were recruited through alcohol treatment centers, along with a set of community comparison families. Nearly 18,000 individuals from >2200 families have been assessed over a period of over 30 years with a rich phenotypic battery that includes semi-structured psychiatric interviews and questionnaire measures, along with DNA collection and electrophysiological data on a large subset. Participants range in age from 7 to 97, with many having longitudinal assessments, providing a valuable opportunity to study alcohol use and problems across the lifespan. Here we provide an overview of data collection methods for the COGA sample, and details about sample characteristics and comorbidity. We also review key research findings that have emerged from analyses of the COGA data. COGA data are available broadly to researchers, and we hope this overview will encourage further collaboration and use of these data to advance the field.     

Photosynthetic induction times in shade-tolerant species with long and short-lived leaves

In the understory of a tropical rainforest, light flecks can contribute 10–80% of the total light flux. We investigated the capacity of eight shade-tolerant species to use light flecks by examining the time required for full induction of photosynthesis during an artificial light fleck. CO₂ fixation rates were measured with a portable LiCor gas-exchange system for plants growing in the field on Barro Colorado Island, Panama. In all species induction to 50% of maximum CO₂ fixation occurred quickly, from 1 to 3 min. In species with short leaf lifetimes (1 year), induction to 90% of maximum also occurred quickly, in 3–6 min. In contrast, the species with longer lived leaves (>4 years) required 11–36 min for induction to 90% of maximum. Induction times for leaves from gap and understory plants of the same species were indistinguishable. Elevated CO₂ did not eliminate the slow induction phase of long-lived leaves. This suggests that slow induction did not result from stomatal limitation. O₂ evolution, measured on excised leaf disks, induced in 3–4 min in species with short-lived leaves, and 4–8 min in species with long-lived leaves. The rapid induction of O₂ evolution indicates that the slower induction of CO₂ fixation in long-lived leaves was not caused by a delay in the induction of electron transport. Activation of rubisco may be the major factor limiting response times in species with long-lived leaves. Species from Panama with short-lived leaves had remarkably rapid induction times that are comparable to those of algae or higher plant chloroplasts. We also found that understory forest plants induced two to seven times more quickly than did potted plants.     

幼虫密度对美国白蛾生活史参数的影响

美国白蛾Hyphantria cunea原产于北美地区,1979年首次在我国辽宁省丹东地区发现,目前已扩散至江苏省南京市等地区,并有进一步扩散的趋势。由于其寄主范围广,适应能力强,危害严重,因此给我国林业生产造成了重大损失。美国白蛾1~4龄幼虫常聚集危害,4龄后开始破网分散危害。本文旨在探明幼虫密度变化对其生活史参数的影响,为解析美国白蛾种群动态变化规律提供科学依据。于温度25℃±1℃和光周期16 L∶8 D条件下,设置5头、10头、20头、40头和80头幼虫/容器5个密度处理组,待幼虫化蛹和成虫羽化后,分别检测幼虫龄期与成活率、蛹的体型（体长和体宽）与体重及成活率、成虫体型（成虫头幅宽度、前翅长度和后足腿节长度）与寿命及繁殖力等生活史参数。结果表明,幼虫密度增加缩短了幼虫发育历期,同时降低了幼虫成活率。幼虫密度增加对蛹重、蛹长、雌蛹宽度及蛹成活率有明显的负效应,但对雄蛹宽度无显著影响。幼虫密度增加对雌虫头幅宽度、雌虫繁殖力、成虫寿命与卵直径具明显负面影响,对雄虫头幅宽度与雌虫前翅长度无显著影响,对成虫后足腿节长度、雄虫前翅长度则具正面影响。因此,本研究表明幼虫密度对美国白蛾不同阶段的生活史参数具调控作用,其中幼虫密度增加对幼虫成活率、蛹的体型与体重及成活率、雌虫繁殖力与卵直径及成虫寿命的负面影响对其种群适合度可能是不利的;然而,成虫对幼虫密度增加会采取一定的适应策略,高密度条件下羽化的成虫具较长的后足腿节与前翅长度以提高其迁移扩散半径,有助于减轻子代种内竞争压力,进而提高种群适合度。     

For better or worse: reduced adult lifespan following early-life stress is transmitted to breeding partners

Stressful conditions early in life can give rise to exaggerated stress responses, which, while beneficial in the short term, chronically increase lifetime exposure to stress hormones and elevate disease risk later in life. Using zebra finches Taeniopygia guttata, we show here that individuals whose glucocorticoid stress hormones were experimentally increased for only a brief period in early post-natal life, inducing increased stress sensitivity, had reduced adult lifespans. Remarkably, the breeding partners of such exposed individuals also died at a younger age. This negative effect on partner longevity was the same for both sexes; it occurred irrespective of the partner's own early stress exposure and was in addition to any longevity reduction arising from this. Furthermore, this partner effect continued even after the breeding partnership was terminated. Only 5 per cent of control birds with control partners had died after 3 years, compared with over 40 per cent in early stress-early stress pairs. In contrast, reproductive capability appeared unaffected by the early stress treatment, even when breeding in stressful environmental circumstances. Our results clearly show that increased exposure to glucocorticoids early in life can markedly reduce adult life expectancy, and that pairing with such exposed partners carries an additional and substantial lifespan penalty.