Aging Genomics: Biological Process and Genetic Factors

Study Notes

Aging is a biological process that converts an optimally healthy, fit organism into a less healthy, less fit one
Aging is not a disease, per se, but rather a process of reduced tissue/physiological function, increased susceptibility to disease, and decreased resistance to stress

Genetic factors play a significant role in determining the aging process and lifespan, more so than environmental factors
Specific genetic disorders, such as Hutchinson-Gilford, Werner's, and Down syndromes, can speed up the aging process

The rate of cell multiplication slows down with age
T-cell lymphocytes, essential for immune function, decrease with age
Age interferes with apoptosis, a process necessary for tissue health and immune response regulation

Cellular senescence is the state or process of aging, characterized by a limited ability to divide in culture (Hayflick Limit)
In humans and animals, cellular senescence is attributed to telomere shortening with each cell cycle, leading to cell death when telomeres become too short

Telomere length serves as a "molecular clock" predicting the aging process
Telomere length is maintained in immortal cells by the telomerase enzyme
In the laboratory, mortal cell lines can be immortalized by activating their telomerase gene

Cancerous cells must become immortal to multiply without limit, often by reactivating their telomerase gene
The telomere "clock" can be seen as a protective mechanism against cancer
The longevity clock might be located in genes on the 1st or 4th chromosome of human chromosomes

The sirtuin family of genes has a significant effect on the lifespan of yeast and nematodes
Over-expression of the RAS2 gene can increase lifespan in yeast substantially

Cancer genomics is the study of the human cancer genome, searching for a full collection of genes and mutations that contribute to the development of a cancer cell and its progression.
It involves studying "cancer families" and patients to identify inherited and sporadic mutations that lead to cancer.

Oncogenes are genes responsible for the cancer phenotype, promoting growth and cell division.
Tumor suppressor genes, on the other hand, suppress growth and cell division.
Viral carcinogenesis in animals has revealed the genetic basis of cancer, with transforming retroviruses carrying genes with oncogenic capabilities.

Human karyotype: the complete set of chromosomes in a human cell.
Genes: units of heredity made up of DNA.
Coding vs. non-coding DNA: coding DNA carries genetic information, while non-coding DNA does not.
Genetic codes: the set of rules that translate DNA sequences into proteins.
Central dogma: the flow of genetic information from DNA to RNA to proteins.
Transcription and translation: the processes of converting DNA into RNA and then into proteins.
Mitosis and meiosis: types of cell division that result in identical or genetically unique daughter cells.
Epigenetic factors: external factors that influence gene expression without changing the DNA sequence.
Mutation: a change in the DNA sequence.

Tumors arise from a single parent cell that has acquired a mutation.
When a cell divides, it passes on the mutation to its progeny.
Cells with cancer-linked mutations tend to proliferate more than normal cells, accumulating and being copied to descendant cells.
All tumors are clonal, originating from a single parent cell.

Majority of human cancers result from the accumulation of somatic mutations, which are not passed on to the next generation.
Somatic mutations occur due to exposures to carcinogens, random errors during cell growth and division, or other factors.
Occasionally, a somatic mutation alters the function of a critical gene, providing a growth advantage to the cell.

A de novo mutation is a new mutation that occurs in a germ cell and is passed on to an offspring.
Inherited mutations had to start somewhere, and that somewhere is a de novo mutation.
De novo mutations are common in a few inherited cancer susceptibility syndromes.

Mutations in non-coding regions can affect gene expression.
Regulatory regions in the 5' non-coding flanking region of the gene, such as promoter sequences and enhancer sequences, can be affected by mutations.
Gene repressor regions can also be affected by mutations, leading to changes in protein production.

In chronic myelogenous leukemia, a translocation occurs between chromosomes 9 and 22, creating a fusion gene called Bcr-Abl.
The Bcr-Abl protein promotes the development of leukemia.
The drug Gleevec blocks the activation of the Bcr-Abl protein.

Cancer can start as a new genotype, or a change in the genetic makeup of a person.
The new genotype ultimately produces a new phenotype, or the physical manifestation of a trait or disease.
Cancer is known for its ever-changing genotypes and phenotypes.