Visualization Of Age Associated Changes In Actin Cables And Mitochondria Case Study

Cytoplasmic streaming is the organised flow of the cytoplasm and its constituents within a living cell (Shimmen et al., 2004). Organelles and important molecules move through the cytosol along the structure of the cytoskeleton (actin filaments and microtubules) with the aid of myosin I, an actin-binding motor protein that plays a part in various cell functions including cell motility and endocytosis (Flavell et al., 2008). Actin microfilaments (F-actin) are the thinnest filaments of the cytoskeleton,

At the National Human Genome Research Institute (NHGRI) they conducted a study on age-related cell damage

1.3: Is the lifespan extension observed in ykl∆ cells due to effects on actin cable stability? Here, the goal is to test whether reducing actin cable stability prevents the lifespan extension produced by deletion of Ykl. We will reduce actin cable stability by mutating tropomyosin. There are two tropomyosin isoforms in yeast, Tpm1 and Tpm2. Both isoforms localize to actin cables. However, Tpm1 stabilizes F-actin in actin cables. In contrast, Tpm2 regulates RACF by inhibiting the binding of myosin to actin within actin cables. Previous studies in mammalian cells indicate that mutations in the actin binding pocket of tropomyosin reduces their ability to bind to and stabilize F-actin. I will generate the same mutations in TPM1 and identify conditions that reduces actin cable abundance to wild-type levels in ykl∆ cells. Lastly, I will test whether restoring the wild-type actin cable levels in ykl∆ cells prevents the lifespan extension originally seen in ykl∆ cells.

elements that play a role in the progression of aging is the decline in satellite cell number,

Question 7: Ca+ would bind to troponin which then allows the G sites in the actin to be exposed causeing myosin heads to form crossbridges which leads to shortening of the sacromere.

in the Nutrition and Metabolic Biology program at Columbia University to explore the connection between nutrients and aging. Aging is an inevitable phenomenon in the human population and contributes to age-associated disorders; however, the root causes of age-associated declines in cellular processes remain unsolved. I joined Dr. Liza Pon’s laboratory to use the power of yeast as a model system to study aging by investigating mother-daughter age asymmetry, the whereby babies are born young, largely independent of the age of their parents. Dr. Pon and her lab established actin cytoskeleton dynamics as an age-determinant, which allows daughter cells to preferentially inherit fitter mitochondria from the mother cell along the actin cytoskeleton. I have also assisted in a related project, which revealed that mitochondrial dynamics also contributes to mitochondrial inheritance through effects on mitochondria anchorage in the bud tip and was recently published in Molecular Biology of the Cell. For my doctoral research, I am characterizing novel open reading frames in the regulation of actin cytoskeleton and mitochondrial quality that results in promoting longevity. The training I received from Dr. Hardwick and MMI have proven crucial in development of my technical and intellectual abilities needed to begin this quest for elucidating a novel mechanism for aging, which can provide insight into future therapies for aging-associated

The western blot containing the three different cell lines expressed an equal amount of actin expressed in all three lanes. This served as a control to ensure the plasmids were inserted correctly and there was no interference of any other gene. The lane with cells from mice group 1 showed darker bands on lines corresponding to the proteins Arg as opposed to the lane with mice group 2 cells. The bands corresponding to the protein Abl appeared to be the same on both lanes, demonstrating that Abl was not being accidentally overexpressed as well. These pieces of information elucidated to us that the Arg gene was being successfully overexpressed in line 1. The bands corresponding to Ras-MAPK were darker for mice group 1 than for group 2, demonstrating that this signal transduction pathway for cell proliferation has been downregulated with the overexpression Arg.

Since our society is facing a strong demographic change towards an elderly population, research focusing on aging is getting more and more attention. However, research proved to be difficult when wanting to identify the different mechanisms, pathways, and processes involved in aging in humans. During aging, physiological and homeostatic functions decrease progressively. Aging results from the interaction of various factors, including genetic background, environment, and stochasticity. Several molecular mechanisms that promote healthy aging have been discovered in model organisms, such as C. elegans. Recent research revealed that extracellular matrix (ECM) integrity declines with aging. This decline correlates with a decline in expression of

It remains to be secured whether manipulations that constrain general protein synthesis affect longevity due to the deteriorated rates of overall protein synthesis. There is overcoming evidence that cellular mechanisms and signaling pathways regulating aging are controlled by mTOR. Above I have mentioned important studies that support a role for both mTOR dependent protein synthesis and autophagy in aging. Further studies are needed to test the importance on human longevity

actin “slid” past each other and neither filament changed in length. In 1957 Allan Huxley

The outcomes of the study, which engaged the use of a extremely accurate biomarker to evaluate biological aging, are presented in Molecular Cell.

Telomerase (TERT) is an enzyme responsible for maintaining the ends of telomeres and reversing the process of telomere shortening in humans by adding a “TTAGGG” polynucleotide to the 3’ end of the telomere. The addition of the “TTAGGG” compensates for inefficiencies in replication of the ends of DNA in eukaryotes. Telomerase is limited to highly proliferative cells such as germ cells and lymphocytes where the telomerase is necessary to maintain telomere length, and the telomeres themselves are not sufficiently long to facilitate such rapid cell division without incurring damage to the DNA. Most somatic cells exhibit no telomerase activity and in cells where telomerase is present telomerase activity is strictly regulated. In cells that exhibit

Ageing affects majority part of the body systems including cells, organs and tissues. It is characterised by the gradual loss of function and eventually affects the whole organism. Many studies on simple model organisms on genetic and molecular biology, many genes and pathways involved in longevity have been identified, helping to depict the molecular scenario of ageing.

Telomeres are directly correlated to the aging of a human body. Although some people might think that shorter telomere lengths are detrimental, the natural shortening of these telomeres are essential to healthy and normal aging. It is natural for cells to divide through mitosis, but each time cells are split telomeres are lost through the process. This is why the telomere maintenance system was evolved to protect the ends of chromosomes (Prescott, Kraft, & Chasman, 2011). Every time a cell is divided, its telomeres are weakened, and stress can accelerate this weakening, and biologically age the person. As a

Aging is the process of becoming older, as we age, multiple mutations occur that concern all the processes of aging well as it compromising a number of different genes. There are many theories of biological aging, such as the Cellular Aging Theory, Immunological Theory, and the Wear and Tear Theory. The Cellular Aging theory describes the process of aging in which cells slow their number of replication, thus giving each species a “biological clock that determines its maximum life span” and how quickly one 's health will deteriorate(Hooyman, 42). After a certain number of years, each cell which follows an apparent biological clock starts to replicate itself less, thus the specific individual or species slowly deteriorates. This theory gives