Cells Yeast

Cells Yeast - Yeast cells are similar to animal cells in their core biochemistry and organelles. We should not be surprised that the 6000 yeast genes include orthologues of insulin-like signaling and other genes in tissue-grade animals (Fig. 1.3A). Fungal genomes diverged from the animals about 1500 million years ago (Cai, 2006). Aging and life span in yeast are studied with two very different experimental models: replicative life span (Piper, 2006; Sinclair et al, 1998) and chronological life span (Fabrizio and Longo, 2003; Fabrizio et al., 2004). The yeast replicative life span is defined by asexual reproduction through the formation of smaller buds on the surface of the mother cell. The intervals between budding lengthen as the replicative life span is approached, at about 20 cell divisions. Oxidatively damaged proteins are retained asymmetrically by the mother cell (Aguilaniu et al, 2003), which may be how the detached buds start the replicative clock at zero, independent of mother cell age. 

sumber: http://www.phys.ksu.edu/gene/photos/lab19.jpg

The replicativelife span model resembles the Hayflick model in that both show limited cloning. The  sterile postreplicative cells may have considerable remaining life span (V. Longo, personal comm). Mechanisms in replicative aging include aunique genomic instability in ribosomal DNA (rDNA) cistrons, through aberrant recombination that causes the accumulation of extra-chromosomal rDNA circles. The rDNA instability is modulated by chromatin condensation under the control of Sir2 (silent information regulator), a NAD-dependent histone deacetylase. Increased Sir2 inhibits the aberrant recombination and extends the replicative life span. Sirtuins and their orthologues have many other metabolic activities in animals (Chapter 3 and 5); e.g., diet restriction activates Sirt1 and modulates lipolysis in mammalian fat (Wolf, 2006).

The chronological life span is defined as the cell viability during prolonged periods with limited external nutrients. Yeast and other autotrophic fungi have evolved adaptive mechanisms in their natural habitats for surviving extended periods of starvation, pending episodes of surfeit. When switched from growth  media to water, yeast cells become hypometabolic, extending their life span several fold to 15–20 days. Mutations in the kinase Sch9 increase life span by increasing stress resistance and glycogen reserves. Sch9, a functional homologue of Akt/PBK, which modulates life span in animals (Fig. 1.3A), also synergizes with Sir2 (Longo and Kennedy, 2006).

Ongoing studies point to the convergence of mechanisms in these seemingly different models, by the shared dependence of replicative and chronological life spans on Sch9, Ras/cyr/PKA, and Tor pathways (Longo and Kennedy, 2006). The formation of rDNA circles may be regarded as a ‘yeast disease of aging’ specific to the replicative senescence mode. Besides these single cell models, yeast can also grow as filaments (pseudohyphae) (Gognies et al, 2006), which enable the invasion of ripe fruit. Dense fungal mats can form, possibly including domains with metabolic gradients. These alternate life history modes with complex morphology have not been studied for aging processes.

Cultured Cell Models and Replicative Senescence

Cultured Cell Models and Replicative Senescence - Unlike cancer cells, diploid somatic cells typically have a finite capacity for propagation during serial culture, shown first for skin fibroblasts (Hayflick and Moorhead, 1961). After a finite number of subcultures (population doublings), cell division ceases and cultures are considered senescent. The ‘Hayflick’ phenomenon extends to many cell types, including vascular endothelia and lymphocytes (Campisi, 2005; Cristofalo et al, 2004; Hayflick, 2000). Although theend-phase cultures are considered ‘senescent,’ post-replicative cells survive many months if media are refreshed (Matsumura et al, 1979). In fact, senescent cultures are highly resistant to apoptosis. Resistance to apoptosis may link back to the insulin pathways that modulate life span (Fig. 1.3), because senescent cell cultures have decreased endocytic uptake of the IGF-binding protein IGFBP-3 (Hampel et al, 2005). It is cogent to Query I that senescent cultures of fibroblasts and other cell types show increased inflammatory factors including COX-2, IL-1, MMP-3, collagenase, TIMP-1 (tissue inhibitor of metaloproteases) (Han et al, 2004; Parrinello et al,2005; West et al, 1989; Zeng et al, 1996). These same changes arise in atheromas and, moreover, are blocked in senescing cultures by the COX-2 inhibitor NS398 (Han et al, 2004) (Chapter 2). Inflammatory factors secreted by replicatively senescent cells are implicated in focal tissue remodeling in the progression of pre-malignant cells (Campisi, 2005).

cultured cells (sumber: stemcells.nih.gov)

Individual cell variations in replicative potential are associated with variable telomere length (Martin-Ruiz et al, 2004). It is not known if telomere heterogeneity causes the daughter cell differences in proliferative potential, which range from 0 (growth arrest) to 15 or more replications (Matsumura et al, 1985). Somatic cell replicative heterogeneity may contribute to the remarkable differences of individual life span in twins and in highly inbred worms (Finch and Kirkwood, 2000) (Section 5.2).

Contrary to earlier conclusions, adult age up to 92 years does not change the Hayflick limit of skin fibroblasts (Cristofalo et al, 2004; Goldstein et al, 1978; Smith et al, 2002). However, cells from embryos or children have 2-fold higher Hayflick limits (Martin, 1970). Thus, the major effect of age on the cell senescence model is before maturation. In vivo exposure to oxidative stress may be a factor in the reduced proliferation of cells from diabetics (Goldstein et al, 1979). Moreover, the standard protocol of culturing cells for aging studies in ambient air (20% oxygen) is grossly unphysiological. When mouse cells were ‘aged’ at 3% oxygen, closer to the tissue levels, their replicative potential was greatly increased (Parrinello et al, 2003). Nonethless, even under the standard culture conditions, in species comparisons, resistance of cultured fibroblasts to oxidative stress correlates with life span (Kapahi et al., 1999). We may anticipate fruitful further analysis of species differences in resistance to oxidative stress that might, in turn, inform about in vivo vulnerability to bystander effects from inflammatory processes.

The Structure and Function of the Cerebrum

The Structure and Function of the Cerebrum - Each half of the cerebrum consists of an internal mass of white matter and a thin, outer covering of grey matter, called the cerebral cortex. Compared to a falcon with its keen eyesight or a dog with its sense of smell, humans lack many sensory capabilities. Due to the evolution of the cerebral cortex, however, humans are considered to have the most sophisticated intellect and behaviour of all animals.

The cerebral cortex is responsible for language, memory, personality, vision, conscious thought, and other activities that are associated with thinking and feeling. The cerebral cortex is about 5 mm thick and, as shown in Figure 11.27, is highly convoluted. This allows it to fi t a high concentration of grey matter within the confi nes of the skull. Relative to a smooth surface, the convolutions and fi ssures greatly increase the surface area, so that the cerebral cortex covers about 0.5 m2, or about the area of an open newspaper.

The right and left halves of the cerebrum are called the cerebral hemispheres. They are linked by a bundle of white matter called the corpus callosum. The corpus callosum sends messages from one cerebral hemisphere to the other, telling each half of the brain what the other half is doing. Surgical isolation of the hemispheres is sometimes used to treat epilepsy, a condition that causes uncontrollable seizures. Scientists think that epilepsy can be caused by an overload of neurological electrical activities, so the corpus callosum is cut to prevent the spread of the epileptic seizures from one hemisphere to the other.

Research indicates that, while every cognitive function contains right-brain and left-brain components, some functions seem to have a dominant hemisphere. In general, the right-brain, or right cerebral hemisphere, is associated with holistic and intuitive thinking, visual-spatial skills, and artistic abilities. The left-brain, or left cerebral hemisphere, is linked to segmental, sequential, and logical ways of thinking, and to linguistic and mathematical skills. This is why people who are right-brain dominant process and learn information differently from people who are left-brain dominant. One way to illustrate the difference between right-brain and left-brain processing is the Stroop effect. rather than the words themselves. This is diffi cult because, as one theory suggests, one side of the brain may dominate in word recognition, while the other side may dominate in colour recognition. In other words, this leads to a right-left brain confl ict!

The Need For Energy

The Need For Energy - All organisms need energy to stay alive. They use this energy to grow, maintain body processes, and reproduce. Many kinds of organisms require energy to move, as well. Energy to support these activities is released in the bodies of organisms from carbohydrates and other energy-rich organic molecules. 

The Need For Energy

In animals, plants, and most other species (kinds) of organisms, the process that releases this energy is cellular respiration. (For a small number of species that live in environments without oxygen, the energy-releasing process is fermentation.) The word equation and chemical equation below summarize the process of cellular respiration.

How is energy stored in energy-rich molecules in the fi rst place? It is stored through the process of photosynthesis. Through photosynthesis, plants, algae, and some kinds of bacteria use the Sun’s light energy to chemically convert carbon into carbohydrates such as sugars and starches. The word equation and chemical equation below summarize the process of photosynthesis.

Cellular respiration and Photosynthesis

Organisms that are able to use the Sun’s energy to produce food for themselves in this way are called producers. Producers are also known as autotrophs, which means “self-feeders.”

The ruby-throated hummingbird and other animals are not able to make the energy-rich molecules they need to fuel their life processes. Instead, they must obtain these molecules by consuming other organisms (or absorbing nutrients from them). Thus, animals and some other kinds of organisms are heterotrophs, which means “other-feeders.” Heterotrophs that consume other heterotrophs or autotrophs are called consumers. 

Genetics, Meiosis, and Cells

Genetics, Meiosis, and Cells - Why do you have a particular blood type or hair color? Why do some people have the same skin color as their parents and others have a skin color different from that of their parents? Why do flowers show such a wide variety of colors? Why is it that generation after generation of plants, animals, and microbes look so much like members of their own kind? These questions and many others can be better answered if you have an understanding of genetics.

Genetic

A gene is a portion of DNA that determines a characteristic. Through meiosis and reproduction, genes can be transmitted from one generation to another. The study of genes, how genes produce characteristics, and how the characteristics are inherited is the field of biology called genetics. The first person to systematically study inheritance and formulate laws about how characteristics are passed from one generation to the next was an Augustinian monk named Gregor Mendel (1822–1884). Mendel’s work was not generally accepted until 1900, when three men, working independently, rediscovered some of the ideas that Mendel had formulated more than 30 years earlier. Because of his early work, the study of the pattern of inheritance that follows the laws formulated by Gregor Mendel is often called Mendelian genetics.

To understand this chapter, you need to know some basic terminology. One term that you have already encountered is gene. Mendel thought of a gene as a particle that could be passed from the parents to the offspring (children, descendants, or progeny). Today we know that genes are actually composed of specific sequences of DNA nucleotides.

The particle concept is not entirely inaccurate, because a particular gene is located at a specific place on a chromosome called its locus (locus = location; plural, loci). Another important idea to remember is that all sexually reproducing organisms have a diploid (2n) stage. Because gametes are haploid (n) and most organisms are diploid, the conversion of diploid to haploid cells during meiosis is an important process.

2(n) → meiosis → (n) gametes

The diploid cells have two sets of chromosomes—one set inherited from each parent.

n + n gametes → fertilization → 2n

Therefore, they have two chromosomes of each kind and have two genes for each characteristic. When sex cells are produced by meiosis, reduction division occurs, and the diploid number is reduced to haploid. Therefore, the sex cells produced by meiosis have only one chromosome of each of the homologous pairs that were in the diploid cell that began meiosis. Diploid organisms usually result from the fertilization of a haploid egg by a haploid sperm. Thus they inherit one gene of each type from each parent. For example, each of us has two genes for earlobe shape: one came with our father’s sperm, the other with our mother’s egg.

Concentration Gradient

Concentration Gradient - The concentration of most molecules inside a cell is different than the concentration of molecules in the surrounding environment. The plasma membrane separates the internal environment of the cell from the fluid bathing the cell and regulates the flow of molecules both into and out of the cell. The second law of thermodynamics states that molecules, whether in the gas or liquid state, will move spontaneously from an area of higher concentration to an area of lower concentration or down their concentration gradient.

Concentration Gradient

A concentration gradient can be likened to water stored behind a dam. The water behind the dam will flow through the dam via any available channel to the other side. The energy from the water moving through the dam can be harnessed to make electricity. Water can also be pumped in the opposite direction from the river below the dam up to the reservoir behind the dam, with an expenditure of energy. Cellular membranes act somewhat like a dam. They block the movement of many types of molecules and have specific channels, transporters and pumps to provide pathways for the movement of certain molecules across the membrane.

When a molecule moves down its concentration gradient using one of these membrane channels or transporters, the process is called facilitated diffusion. In facilitated diffusion, no input of energy is needed to move the molecules. Instead, the potential energy of the concentration gradient powers the movement, just like water flowing out of a dam. For further diffusion, the channel or transporter does not determine in which direction the molecules will move, it only provides a pathway for the movement.

In cells, some molecules must be moved against their concentration gradient to increase their concentration inside or outside the cell. This process requires the input of energy and is known as active transport. As with facilitated diffusion, special transporters in the membrane are used to move the olecules across the membrane. The plasma membrane is not the only cellular membrane that requires active transport. All organelles surrounded by membranes must concentrate some molecules against their concentration gradients.