ALLELE: One of several possible versions of a gene. Each one contains a distinct variation in its DNA sequence. For example, a “deleterious allele” is a form of a gene that leads to disease.
AMINO ACID: The chemical building block of proteins. During translation, different amino acids are strung together to form a chain that folds into a protein.
ANTAGONISTIC PLEIOTROPY: A theory proposed by George C. Williams as an evolutionary explanation for aging: a gene that reduces lifespan in late life can be selected for if its early benefits outweigh its late costs. An example of this is the survival circuit.
BASE: The four “letters” of the genetic code, A, C, T, and G, are chemical groups called bases or nucleobases. A= adenine, C = cytosine, T = thymine, and G = guanine. Instead of thymine, RNA contains a base called uracil (U).
BASE PAIR: “Teeth” on the twisted “zipper” of DNA. Chemicals known as bases make up a DNA strand, each strand runs in the opposite direction, and bases attract their opposite partner to make a base pair: C pairs with G, A pairs with T (except for in RNA, where it’s a U).
BIOTRACKING/BIOHACKING: The use of devices and lab tests to monitor the body to make decisions about food, exercise, and other lifestyle choices to optimize the body. Not to be confused with biohacking, which is do-it-yourself body enhancement.
CANCER: A disease caused by uncontrolled growth of cells. Cancerous cells may form clumps or masses known as tumors and can spread to other parts of the body through a process known as metastasis.
CELL: The basic unit of life. The number of cells in a living organism ranges from one (e.g., in yeast) to quadrillions (e.g., in a blue whale). A cell is composed of four key macromolecules that allow it to function: protein, lipids, carbohydrates, and nucleic acids. Among other things, cells can build and break down molecules, move, grow, divide, and die.
CELLULAR REPROGRAMMING: The changing of cells from one type of tissue to a prior stage of development.
CELLULAR SENESCENCE: The process that occurs when normal cells stop dividing and start to release inflammatory molecules, sometimes caused by telomere shortening, damage to DNA, or epigenomic noise. Despite their seeming “zombie” state, senescent cells remain alive, damaging nearby cells with their inflamatory secretions.
CHROMATIN: Strands of DNA wound around protein scaffolds known as histones. Euchromatin is open chromatin that allows genes to be switched on. Heterochromatin is closed chromatin that prevents the cell from reading a gene, also known as gene silencing.
CHROMOSOME: The compact structure into which a cell’s DNA is organized, held together by proteins. The genomes of different organisms are arranged into varying numbers of chromosomes. Human cells have 23 pairs.
COMPLEMENTARY: Describes any two DNA or RNA sequences that can form a series of base pairs with each other. Each base forms a bond with a complementary partner: T (in DNA) and U (in RNA) bond with A, and C bonds with G.
CRISPR: Pronounced “crisper.” An immune system found in bacteria and archaea, co-opted as a genome-engineering tool to cut DNA at precise places in a genome. CRISPR, which stands for “clustered regularly interspaced short palindromic repeats,” is a section of the host genome containing alternating repetitive sequences and snippets of foreign DNA. CRISPR proteins such as Cas9, a DNA-cutting enzyme, use these as molecular “mug shots” as they seek out and destroy viral DNA.
DAF-16/FOXO: An ally of sirtuins, DAF-16/FOXO is a gene control protein called a transcription factor that activates cell defense genes, upregulation of which extends lifespan in worms, flies, mice, and perhaps humans; required for Daf-2 to extend lifespan in worms.
DEACETYLATION: The enzymatic removal of acetyl tags from proteins. Removal of acetyls from histones by histone deacetylases (HDACs) causes them to be more tightly packed, switching off a gene. Sirtuins are NAD-dependent deacetylases. Deacylation is a catchall term that includes deacetylation and the removal of other, more exotic tags such as butyryls and succinyls.
DEMETHYLATION: Demethylation is the removal of methyls and is carried out by enzymes called histone demethylases (KDMs) and DNA demethylases (TETs). Attachment of methyls is achieved by a histone or DNA methyltransferases (DMTs).
DISPOSABLE SOMA: A hypothesis proposed by Tom Kirkwood to explain aging. Species evolve to grow and multiply quickly or build a long-lasting body, but not both; limited resources in the wild don’t allow for both.
DNA: Abbreviation of deoxyribonucleic acid, the molecule that encodes the information needed for a cell to function or a virus to replicate. Forms a double-helix shape that resembles a twisted ladder, similar to a zipper. Bases, abbreviated as A, C, T, and G, are found on each side of the ladder, or strand, which run in opposite directions. The bases have an attraction for each other, making A stick to T and C stick to G. The sequence of these letters is called the genetic code.
DNA DOUBLE-STRAND BREAK (DSB): What happens when both strands of DNA are broken and two free ends are created. May be done intentionally with an enzyme such as Cas9 or I-PpoI. Cells repair their DNA to prevent cell death, sometimes changing the DNA sequence at the site of the break. Initiating or controlling this process with the intent to alter a DNA sequence is known as genome engineering.
DNA METHYLATION CLOCK: Changes in the number and sites of DNA methylation tags on DNA can be used to predict lifespan, marking time from birth. During epigenomic reprogramming or cloning of an organism, methyl marks are removed, reversing the age of the cell.
ENZYME: A protein made up of strings of amino acids that folds into a ball that can carry out chemical reactions that would normally take much longer or otherwise never happen. Sirtuins, for example, are enzymes that use NAD to remove acetyl chemical groups from histones.
EPIGENETIC: Refers to changes to a cell’s gene expression that do not involve altering its DNA code. Instead the DNA and the histones that the DNA is wrapped around are “tagged” with removable chemical signals (see Demethylation and deacetylation). Epigenetic marks tell other proteins where and when to read the DNA, comparable to sticking a note that says “Skip” onto a page of a book. A reader will ignore the page, but the book itself has not been changed.
EPIGENETIC DRIFT AND EPIGENETIC NOISE: Alterations to the epigenome that take place with age due to changes in methylation, often related to an individual’s exposure to environmental factors. Epigenomic drift and noise may be a key driver of aging in all species. Damage to DNA, especially DNA breaks, is a driver of this process.
EXDIFFERENTIATION: The loss of cell identity due to epigenetic noise. Exdifferentiation may be a major cause of aging (see Epigenetic Noise).
EXTRACHROMOSOMAL RIBOSOMAL DNA CIRCLE (ERC): The generation of extrachromosomal ribosomal DNA circles leads to the breaking apart of the nucleolus in old cells, and in yeast they distract the sirtuins and cause aging.
GENE: A segment of DNA that encodes the information used to make a protein. Each gene is a set of instructions for making a particular molecular machine that helps a cell, organism, or virus function.
GENE EXPRESSION: A product based on a gene; can refer to either RNA or protein. When a gene is turned on, cellular machines express this by transcribing the DNA into RNA and/or translating the RNA into a chain of amino acids. For example, a highly expressed gene will have many RNA copies produced, and its protein product is likely to be abundant in the cell.
GENE THERAPY: The delivery of corrective DNA to human cells as a medical treatment. Certain diseases can be treated or even cured by adding a healthy DNA sequence into the genomes of particular cells. Scientists and doctors typically use a harmless virus to shuttle genes into targeted cells or tissues, where the DNA is incorporated somewhere within the cells’ existing DNA. CRISPR genome editing is sometimes referred to as a gene therapy technique.
GENETICALLY MODIFIED ORGANISM (GMO): An organism that has had its DNA altered intentionally using scientific tools. Any organism can be engineered in this manner, including microbes, plants, and animals.
GENOME: The entire DNA sequence of an organism or virus. The genome is essentially a huge set of instructions for making individual parts of a cell and directing how everything should run.
GENOMICS: The study of the genome, all the DNA of a given organism. Involves a genome’s DNA sequence, the organization and control of genes, the molecules that interact with the DNA, and the way in which these different components affect the growth and function of cells.
GERM CELLS: The cells involved in sexual reproduction: eggs, sperm, and precursor cells that develop into eggs or sperm. The DNA in germ cells, including any mutations or intentional genetic edits, may be passed down to the next generation. Genome editing in an early embryo is considered to be germline editing since any DNA changes will likely end up in all cells of the organism that is eventually born.
HISTONES: The proteins that form the core of DNA packaging in the chromosome and the reason three feet of DNA can fit inside a cell. DNA wraps around each histone almost two times, like beads on a string. The packaging of histones is controlled by enzymes such as the sirtuins that add and subtract chemical groups. Tight packaging forms “silent” heterochromatin, while loose packaging forms open euchromatin, where genes are turned on.
HORMESIS: The idea that whatever doesn’t kill you makes you stronger. A level of biological damage or adversity that stimulates repair processes that provide cell survival and health benefits. Originally discovered when plants were sprayed with diluted herbicide and afterward grew faster.
INFORMATION THEORY OF AGING: The idea that aging is due to the loss of information over time, primarily epigenetic information, much of which can be recovered.
METFORMIN: A molecule derived from the French hellebore used to treat type 2 (age-associated) diabetes that may be a longevity medicine.
MITOCHONDRIA: Often called the cell’s powerhouse, mitochondria break down nutrients to create energy in a process called cellular respiration. They contain their own circular genome.
MUTATION: A change from one genetic letter (nucleotide) to another. Variation in the DNA sequence gives rise to the incredible diversity of species among different organisms of the same genus. Though some mutations have no consequences at all, others can directly cause disease. Mutations may be caused by DNA-damaging agents such as ultraviolet light, cosmic radiation, or DNA copying by enzymes. They can also be created deliberately via genome-engineering methods.
NAD: Nicotinamide adenine nucleotide, a chemical used for more than five hundred chemical reactions and for sirtuins to remove acetyl groups of other proteins such as histones to turn genes off or give them cell protective functions. A healthy diet and exercise raise NAD levels. The “+” sign you sometimes see, as in NAD+, indicates that it is not carrying a hydrogen atom.
NUCLEASE: An enzyme that breaks apart the backbone of RNA or DNA. Breaking one strand generates a nick, and breaking both strands generates a double-strand break. An endonuclease cuts in the middle of RNA or DNA, while an exonuclease cuts from the end of the strand. Genome engineering tools such as Cas9 and I-PpoI are endonucleases.
NUCLEIC ACIDS OR NUCLEOTIDES: The basic chemical units that are strung together to make DNA or RNA. They consist of a base, a sugar, and a phosphate group. The phosphates link with sugars to form the DNA/RNA backbone, while the bases bind to their complementary partners to form base pairs.
NUCLEOLUS: Located inside the nucleus of eukaryotic cells, the nucleolus is a region where the ribosomal DNA (rDNA) genes are situated and where the cellular machines for stitching together amino acids to form proteins are assembled.
PATHOGEN: A microbe that causes illness. Most microorganisms are not pathogenic to humans, but some strains or species are.
PROTEIN: A string of amino acids folded into a three-dimensional structure. Each protein is specialized to perform a specific role to help cells grow, divide, and function. Proteins are one of the four macromolecules that make up all living things (proteins, lipids, carbohydrates, and nucleic acids).
RAPAMYCIN: Also known as sirolimus, rapamycin is a compound with immunosuppressant functions in humans. It inhibits activation of T cells and B cells by reducing their sensitivity to the signaling molecule interleukin-2. Extends lifespan by inhibiting mTOR.
REDIFFERENTIATION: The reversal of epigenetic changes that occur during aging.
RIBOSOMAL DNA (rDNA): A key component of the manufacture of new proteins within cells; the source of the genetic code for ribosomal RNA, which is the building block of the ribosome. These molecules knit together amino acids that become new proteins.
RNA: Abbreviation of ribonucleic acid. Transcribed from a DNA template and typically used to direct the synthesis of proteins. CRISPR-associated proteins use RNAs as guides to find matching target sequences in DNA.
SENOLYTICS: Pharmaceuticals currently under development that are hoped to kill senescent cells in order to slow down or even reverse aging-related issues.
SIRTUINS: Enzymes that control longevity; they are found in organisms from yeast to humans and need NAD+ to function. They remove acetyl and acyl groups from proteins to instruct them to protect cells from adversity, disease, and death. During fasting or exercise, sirtuin and NAD+ levels increase, which may explain why those activities are healthy. Named after the yeast SIR2 longevity gene, SIRT1–7 (Sir2 homologs 1 to 7) genes in mammals play key roles in protecting against disease and deterioration.
SOMATIC CELLS: All the cells in a multicellular organism except for germ cells (eggs or sperm). Mutations or changes to the DNA in the soma will not be inherited by subsequent generations unless cloning takes place.
STEM CELLS: Cells with the potential to turn into a specialized type of cell or divide to make more stem cells. Most cells in your body are differentiated; that is, their fate has already been decided and they cannot morph into a different kind of cell. For example, a cell in your brain cannot suddenly transform into a skin cell. Adult stem cells replenish the body as it becomes damaged over time.
STRAND: A string of connected nucleotides; can be DNA or RNA. Two strands of DNA can zip together when complementary; bases match up to form base pairs. DNA typically exists in this double-stranded form, which takes the shape of a twisted ladder or double helix. RNA is typically composed of just a single strand, though it can fold up into complex shapes.
SURVIVAL CIRCUIT: An ancient control system in cells that may have evolved to shift energy away from growth and reproduction toward cellular repair during times of adversity. After response to adversity, the system may not fully reset, which, over time, leads to a disruption of the epigenome and loss of cell identity leading to aging (see Antagonistic Pleiotropy).
TELOMERES/TELOMERE LOSS: A telomere is a cap that protects the end of the chromosome from attrition, analogous to the aglet at the end of a shoelace or a burned end of a rope to stop it fraying. As we age, telomeres erode to the point where the cell reaches the Hayflick limit. This is when the cell regards the telomere as a DNA break, stops dividing, and becomes senescent.
TRANSCRIPTION: The process by which genetic information is copied into a strand of RNA; performed by an enzyme called RNA polymerase.
TRANSLATION: The process by which proteins are made based on instructions encoded in an RNA molecule. Performed by a molecular machine called the ribosome, which links together a series of amino acid building blocks. The resulting polypeptide chain folds up into a particular 3D object, known as a protein.
VIRUS: An infectious entity that can persist only by hijacking a host organism to replicate itself in. Has its own genome but is technically not considered a living organism. Viruses infect all organisms, from humans to plants to microbes. Multicellular organisms have sophisticated immune systems that combat viruses, while CRISPR systems evolved to stop viral infection in bacteria and archaea.
WADDINGTON’S LANDSCAPE: A biological metaphor for how cells are endowed with an identity during embryonic development in the form of a 3D relief map. Marbles representing stem cells roll down into bifurcating valleys, each of which marks a different developmental pathway for the cells.
XENOHORMESIS HYPOTHESIS: The idea that our bodies evolved to sense the stress cues of other species, such as plants, in order to protect themselves during times of impending adversity. Explains why so many medicines come from plants.
