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Glossary of Terms

95% confidence interval: This is the range of values above and below an estimate of risk, within which the actual risk has a 95% probability of failing by chance alone. Thus, if the 95% confidence interval for a risk does not include 1.0 (1.0 is always the risk for the control group), then there is less than a 5% chance that the risk estimated for treatment is not meaningfully different from that of a control group.

Adenosine triphosphate (ATP): The high energy chemical that is used for all energy requiring processes in our cells.

Aging: A gradual and relentless process by which sexually-reproducing organisms lose their youthful capacity for homeostasis. Aging doesn't normally begin until the completion of a characteristic interval of reproductive competence during which a species rears its progeny to independence (see Life History). As a result of aging, older organisms are increasingly vulnerable to a wide variety of age-related diseases, ultimately culminating in their death. The tradeoff between aging and repair processes is extremely complex and observed to operate systematically within a hierarchy of at least seven different interacting levels: (1) molecules; (2) organelles (small membrane-bound cellular components with specialized functions); (3) cells; (4) tissues of various architectures; (5) organs; (6) organ systems; and ultimately (7) the entire organism. Aging occurs silently from within, in the same sense that termites, if unchecked, will ultimately destroy the structural integrity of a large wooden house.

Anthocyanins: Any of a variety of polycyclic compounds, with nitrogen in some rings and most with nitrogen side groups, and double bonds between some of the carbon atoms. These compounds absorb light selectively so that they tend to be highly colored (usually purple, blue, or red). They are found in high concentrations in colored vegetables and most are effective antioxidants.

Antioxidant: One of many types of molecule in our cells which can safely combine with oxygen free radicals, thus rendering them harmless.

Apoptosis: Programmed Cell Death (PCD). This process gets rid of unneeded cells and is particularly important for "sculpting" tissue and organ structure during development of the embryo (or larval metamorphosis in insects), but may occur at any time even in adult cells when a tissue needs to be remodeled. Signals to trigger apoptosis may come from within the cell or from outside, by stimulating suicide receptors in the cell's external membrane. Internal signals producing apoptosis depend on interactions of several proteins and may serve to protect the organism from cancer by killing cells that have pre-cancerous changes.

Atherosclerosis: A deposition of plaques containing cholesterol and lipids on the innermost layer of the walls of arteries.

Average Life Expectancy: The age at which 50 percent of the members of a population have died, when plotted on a standard survival curve. This statistic is normally calculated from birth, but may be recomputed in terms of expected years remaining at any age.

Baseline procedures: A set of critical observations or data used for comparison or control.

Basal Metabolic Rate: (BMR or resting metabolic rate/resting energy expenditure RMR/REE) The rate at which an individual uses oxygen at rest. Associated with the amount of active body composition, usually directly related to fat-free mass, and determines the minimal amount of calories required (amount of food) to sustain your current body mass.

Bases: These are molecules with one or two nitrogen containing ring structures. The biologically important bases are the purines Adenine and Guanine and the pyrimidines Cytosine, Thymine, and Uracil. DNA and RNA are composed of linked sequences of nucleotides, which are molecules each of which consists of a purine or pyrimidine base, a ribose or desoxyribose sugar, and a phosphate group. In DNA, the purine nucleotides are Adenosine (A) and Guanidine (G); the pyrimidine nucleotides are Thymidine (T) and Cytidine (C). In RNA, the pyrimidine nucleotide Uridine (U) is substituted for Cytosine.

Biomarker: A measurable parameter of physiological age that is a more useful predictor of remaining life expectancy than chronological age. The ability to measure biomarkers is extremely important in evaluating the efficacy of any potential life-extending intervention.

Bis-phosphonates: A class of drugs that help to stabilize calcium in bone (alendronate and risedronate are two bis-phosphonate drugs currently FDA-approved for the treatment of osteoporosis).

Body Composition: Refers to the fat and nonfat tissues (lean/muscle mass, bone content and total body water) in your body.

Body Mass Index (BMI): A measure of body composition (fatness) based upon height and weight that applies to men and women.

Caloric Restriction (CR): A diet in which calorie intake is reduced, compared with ad libitum (eat as much as you like) diets, without any reduction in nutritional requirements (protein, water, vitamins, or minerals). CR is not the same as starvation or famine. CR is the only known intervention that systematically extends maximum lifespan. CR has been effective in all species in which it has been tried (although the jury is still out on humans).

Cancer: A clonal growth (cells all descended from one ancestral cell) that undergo continuing mitotic divisions and are not inhibited in their growth when they come in contact with neighboring cells (contact inhibition). Thus, cancers obliterate the normal architecture of the host tissue. Cancer cells often spread (or metastasize) throughout the body by way of the blood stream or lymphatic vessels to form tumors in new locations beyond the primary site of origin. Cells become cancerous by accumulating, stepwise, a series of several mutations that alter the function of genes important for cell growth.

Carcinogens: A substance or agent causing cancer.

Carotid Intimal Medial Thickness (CIMT): An ultrasound that measures the thickness of the inner layers of the wall of the carotid artery.

Cardiorespiratory Endurance: The ability to perform aerobic tasks at an intensity above a normal walking pace for a prolonged period of time.

Carotid Artery: Main arteries that supply blood to the head.

Catalase: An enzyme in our cells which combines 2 hydrogen peroxide molecules to form water and diatomic oxygen (O2).

Chromosome: The structures in the nucleus of the cell, consisting of DNA bound to histones and other proteins. The genes are made of DNA (although the majority of the DNA sequence is not part of any gene). Genes are arranged along the chromosomes in a continuous sequence. Chromosome protein structure allows for selective activation (genes are transcribed into protein) or silencing (genes are not expressed), and thus for differential expression of the genome in different cell types and expression of genes in appropriate sequences during development of the organism or under various metabolic conditions. Chromosomes exist in pairs, one inherited from the mother (egg) and the other from the father (sperm). Thus, normal somatic cells carry two, usually slightly different, versions of each gene (alleles) and are called diploid, while the germ-line cells are called haploid.

Cloning: The use of the chromosomes from an adult cell to create an identical twin (copy) of an organism by inserting the adult nucleus into an egg from which the nucleus has been removed, stimulating embryogenesis, and implanting the embryo into the uterus of a surrogate mother. Reproductive cloning of sheep, goats, cows, pigs, and mice have been widely accomplished. However, attempts at cloning dogs, cats, and horses have not yet met with success. Laws banning human reproductive cloning have been proposed in many countries, including the US. Therapeutic cloning (without the intent to implant the embryo into a surrogate mother) but with the aim of creating a large collection of embryonic (totipotent/pluripotent) stem cells to treat the original donor is a potentially significant medical intervention for the future.

Conjugated Equine Estrogens (CEE): Mixed estrogens mainly composed of sulfate salts and derived from pregnant mare urine.

Coronary Vascular Disease (CVD): A disease affecting the heart and/or the body’s entire system of blood vessels, usually linked to a build-up of fatty plaques in blood vessels.

C-reactive protein: A byproduct of inflammation that is found in blood in some cases of inflammation.

Dementia: The deterioration of intellectual faculties, such as memory, concentration, and judgment.

Deep vein thrombosis (DVT): The formation of clots in the large veins of the leg, also called "thrombophlebitis." This problem can occur if blood flow in the legs is slowed or in certain other conditions in which tendency of the blood to clot is increased. Estrogens taken by mouth cause an increase in blood clotting factors.

Diabetes Mellitus: A medical condition in which the body cannot regulate blood sugars effectively (glucose intolerance) due to either the lack of insulin production (Type I Diabetes) or a failure of cells to respond to insulin signaling (Insulin Resistance or Type II Diabetes).

Dual X-ray Absorptiometry (DEXA): A technique employing X-rays and computer processing to measure density of body tissues precisely.

DHEA (dehydroepiandrosterone): A steroid molecule released from the adrenal gland which is aprecursor for androgens and estrogens, but has no known hormonal actions of its own.

DNA — Deoxyribonucleic Acid: Double stranded DNA molecules consist of antiparallel (running in opposite directions) chains of nucleotides in which the sugar is deoxyribonucleic. The chains are arranged in a double helix with the two chains wrapped around each other and bound together so that each "A" is paired with a "T" (A:T pair) and each "G" is paired with a "C" (G:C pair). Thus, when the chains unwind and separate, new identical antiparallel sequences can be copied along their lengths. DNA is thus self-replicating.

Disposable Soma: From an evolutionary point of view, the prime directive of any organism is to transform available energy from the environment into the maximum number of progeny. Part of the energy is consumed in the maintenance of the organism's somatic (body) tissues (for growth and repair of injury) and part is used to propagate the germ-line tissues. Natural selection favors genetic combinations that produce the most efficient trade-off between these two forms of energy utilization in such a fashion as to maximize evolutionary fitness (i.e., reproductive performance). As a consequence, less energy is directed to somatic maintenance than would be required for the indefinite survival of any individual. This results in the death of individuals, but the immortality of the germ line. The details of the trade-off are largely a function of the ecological niche in which the organism propagates, including predators, prey, parasites, and other environmental factors. According to this theory, the least energy would be devoted to somatic maintenance in a hazardous niche; conversely, more energy would be dedicated to somatic renewal in a relatively protected niche.

Electrocardiogram (EKG/ECG): A test that produces tracings of the heart's electrical activity.

Electron Beam Tomography (EBT): A form of computed axial tomography (CAT) that is considered to be one of the major screening devices for the detection of coronary artery disease.

Endometrial Hyperplasia: An abnormal thickening of the endometrium caused by excessive cell growth.

Epidemiology: A branch of medical science that deals with the incidence, distribution, and control of disease in a population.

Estradiol: A hormone produced by the ovaries and used in treating estrogen deficiency.

Estrogen: A female steroid sex hormone.

Evidence-Based Medicine: The practice of medicine with treatment recommendations that have their origin in objective tests of efficacy published in the scientific literature rather than anecdotal observations.

Fecundity: The ability to produce offspring. High fecundity means the ability to produce progeny rapidly and in large numbers. In the demography of human populations, fecundity is the physiological ability to reproduce, as opposed to fertility.

Fertility: Reproductive Potential. In demography, the number of births per year divided by the number of women of childbearing age, expressed as a rate.

Flavonoids: Compounds widely distributed in nature as pigments in flowers, fruit, vegetables, and tree barks. Some flavonoids have biological activities and may make a useful contribution to the total antioxidant activity of foods.

Free Testosterone: That fraction of testosterone in the blood which is not bound to protein and is thus available to enter cells and act on them.

Geriatrics: A branch of Internal Medicine concerned with the care and treatment of older persons and the treatment and amelioration of diseases of old age and frailty.

Gerontology: A branch of biology focusing on the common mechanisms of aging across all multicellular species. Gerontologists, for example, are keen to understand species that appear to exhibit very gradual or negligible senescence over a long time interval. In this context, gerontologists may study yeast, worms, fruit flies, mice, rock fish, tortoises, bats, parrots, humans, and other creatures exhibiting exceptional longevity.

Gene: A sequence of DNA that can be activated and copied into messenger RNA or mRNA (by a process known as transcription). mRNA is processed and then translated by ribosomes into a sequence of amino acids, which are joined together by peptide bonds to form a protein at cell organelles called endoplasmic reticulum Each triplet of bases (or codon) in mRNA specifies a different amino acid (out of 20 possible choices). It's this sequence of amino acids that determines the identity of a protein (its primary structure). The folding pattern (secondary, tertiary, and quartinary structure) of the primary sequence determines its three-dimensional morphology and ultimately its function (e.g., a structural vs. an enzymic function).

Genotype: The genetic makeup of a cell, organism or group of organisms, with respect to a single trait or group of traits; the sum total of genes transmitted from parents to their offspring.

Genome: The complete collection of genes in the nucleus of each cell of our bodies. There are approximately 35,000 known genes in the human genome.

Gerontome: The subset of the genome whose genes affect longevity, either significantly reducing or increasing the average lifespan of an organism.

Glucose Intolerance: A medical condition in which the body is unable to efficiently remove sugars from the blood following a meal; See Diabetes Mellitus.

Glycemic Control: The ability of the body to regulate sugars; See Diabetes Mellitus.

Glycolytic/Glycolysis: The enzymatic breakdown of phosphate derivatives with the production of pyruvic or lactic acid and energy stored in high-energy phosphate bonds of ATP.

Gompertz Model: A class of statistical models first proposed by the nineteenth-century British actuary Benjamin Gompertz, in which the hazard rate for death rises geometrically with increasing age of the organism (at least after an initial period of high risk of mortality at birth and infancy and a much lower risk in late childhood and adolescence). Today, the Wibel Model is a successor to the Gompertz Model, as it more accurately explains the observed demographic data.

Grandparenting Hypothesis: This is the supposition that abruptly terminates reproduction at a particular age (menopause). Prolonged survival of human females after menopause may have been selected because of better success in child-rearing (and hence survival of the gene pool) when older women focus their resources on the welfare of their grandchildren; therefore increasing their likelihood of survival, rather than investing energy in producing more children of their own and potentially compromising the reproductive success of their adult progeny.

Growth Hormone (GH): A powerful peptide hormone made by the pituitary gland which stimulates growth of muscle, cartilage, bone, and other tissues.

Hayflick Limit: The limit to the number of times a cell can divide during serial cell culture. The value of this limit as a predictor of maximum lifespan of the organism is still unproven. In cultures of normal human fibroblasts, for example, the Hayflick Limit = 50 (± 10) cell doublings. Cancer cells grown in culture, however, exhibit no such limit and continue to divide indefinitely. Normal cells grown in culture that have been instructed to manufacture telomerase (to relengthen their chromosomal telomeres after each division) can achieve replicative immortality and do not obey the Hayflick Limit, but they do not appear to manifest other pathological characteristics of a cancer cells (like loss of contact inhibition).

High density lipid cholesterol (HDL) cholesterol: This is the "good" cholesterol. High levels appear to pull cholesterol out of plaques in the artery walls.

Homeostasis: The physiological capacity of an organism to regulate itself by rapidly restoring internal conditions following a sudden perturbation in the external environment.

Hormones: Natural chemical regulators of cell activities made in glands and released into the blood.

Hypertension: Abnormally elevated blood pressure.

Hysterectomy: The surgical removal of the uterus.

Informed Consent: The consent by a patient to a surgical or medical procedure or participation in a clinical study after achieving an understanding of the relevant medical facts and the risks involved.

Insulin-like Growth Factor I, IGF-I: A peptide molecule that resembles insulin, made in tissues in response to growth hormone which stimulates cell growth and differentiation.

Lean Body Mass (LBM): The amount of total body substance which is not fat (bone, muscle, etc.)

Life History: The combination of age-specific survival probabilities and fertilities characteristic of a species; the time-table of individual development and aging for an organism (e.g., in humans, from embryogenesis, to organogenesis, fetogenesis, birth, infancy, adolescence, puberty, adulthood, menopause, loss of vitality, frailty, and ultimately, death).

Lifespan: The maximum lifespan of a species is the characteristic observed age of death for its very oldest individual(s) (e.g., for humans 120 - 125 years). On the other hand, average lifespan is the age at which 50 percent of the members of a species or group has died. Over the last two centuries, average life expectancy has risen significantly, while maximum lifespan has hardly changed, if at all.

Lipoprotein: Any of a large class of particles composed of a complex of protein and lipid (fatty) molecules and separable on the basis of solubility and mobility properties.

Longevity Genes: Genes that extend the maximum lifespan of a species.

Low density lipid (LDL) cholesterol: This is the "bad" cholesterol. High levels appear to promote formation of plaques in the artery walls.

Lutein: An orange xanthophyll occurring in plants usually along with carotenes and chlorophylls and in animal fat, egg yolk.

Lycopenes: A carotenoid pigment that is the red coloring matter of the tomato.

Macronutrient: Nutrients that living organisms need in relatively large amounts to sustain growth and health (such as protein and carbohydrates).

Macular Degeneration: A loss of central vision produced by retinal damage due to deterioration of blood vessels.

Mammogram: An X-ray examination of the breasts for detection of tumors.

Maximum Lifespan Potential: The longest that any member of a species can live, based on its genetic potential for longevity.

Mean Lifespan: The length of time at which half of a population born at the same time has died.

Medroxyprogesterone acetate: This chemical compound is a synthetic progestogen. It resembles the natural human compound, progesterone, in that it matures the lining of the uterus, but it also appears to have actions in the body that are different from natural progesterone. It has been widely used to protect the uterus from estrogen during menopausal hormone therapy.

Metabolic Equivalent (MET): A measure of energy consumption used for expressing resting metabolic rate.

Menopause: The period marked by the natural and permanent cessation of menstruation.

Micronutrients: Any essential dietary element that is required only in small quantities in order to sustain growth and health.

Mimetic: Stimulating the action or effect of—usually used in combination.

Mitochondria: The tiny energy factories in our cells that combine oxygen and sugar to produce a high energy compound that is needed for all cell activities.

Monounsaturated Fat: Fat molecules that have hydrogen removed from one pair of carbon atoms in their fatty acid chains, so they have one double bond.

Muscular Endurance: The ability of the muscles to perform a heavy task a repeated number of times.

Muscular Strength: The ability of the muscles to generate force or lift a heavy object through a pain-free range of motion without sustaining injury.

Mutation: Any change in DNA structure which alters the established order of the bases. This may cause a gene (or series of genes) to fail to be activated normally (either to be silenced or, the opposite, to be expressed inappropriately) or may cause a gene to express a protein with abnormal structure (and hence abnormal function). Most mutations that have any effect are deleterious. Rarely, mutations may produce some advantage for the organism carrying them. Alleles with advantageous mutations are selected for and tend to become more common in the species' genome. The opposite is true for deleterious mutations. Some mutations move the cell carrying them toward a malignant phenotype (cancer).

Omega-3 Polyunsaturated Fatty Acid: A fatty acid with the first double bond 3 carbons from the end of the molecule, thought to have significant health benefits based on many research studies; high quantities are found in cold water fish and certain seeds, nuts, and vegetables.

Oxidative Stress: Describes the state or rate of ongoing damage to cells and tissues in an organism due to reactive oxygen species (ROS). The most common forms of ROS, such as superoxide and hydroxyl free radicals, are generated from the metabolism of oxygen for energy production and exist in all aerobic organisms. Some toxins from the environment (such as cigarette smoke) also contain or generate ROS. The net damage rate depends on the balance between ROS generation and organismal defense and repair.

Pap smear: A test for cancer of the uterine cervix, in which a smear of exfoliated cells is examined.

Partially Saturated Fat: Polyunsaturated fat molecules which have had hydrogen added back under a high pressure and heat process to change some double bonds to single bonds.

Peptides: Short chains of amino acids (a smaller version of a protein molecule).

Phenotype: The external manifestations of gene expression whether at the level of the cell (e.g., muscle cells are long and thin and contain contractile fibrils; nerve cells have excitable membranes and communicating processes) or the organism (e.g., the giraffe has a long neck; a leopard, spots, and humans of Asian descent, black hair).

Physical Activity: Any bodily movement that requires energy.

Phytochemicals: Technically, the term "phytochemical" refers to any chemical produced by a plant. This term usually refers to certain plant chemicals (such as carotinoids) that scientists believe may impart health benefits.

Placebo: An inactive substance or preparation used as a control in an experiment or test to determine the effectiveness of a medicinal drug.

Plaques: The hardened, swollen areas on the inner wall of an artery where cholesterol and inflammatory cells have altered and damaged the normal smooth surface.

Polycyclic: Multiple 5 and 6 membered rings of carbon atoms joined together.

Polyunsaturated Fat: Fat molecules that have some of the hydrogen removed allowing carbon atoms in their fatty acid chains have double instead of single bonds linking them together. C-C (single bond) C=C (double bond).

Proanthocyanidins: Anthocyanins linked together into chains as polymers (i.e. "giant molecules" whose subunits are other molecules).

Progeria: A human disease or syndrome in which some characteristics of senescence are accelerated so that relatively young individuals appear prematurely aged. Examples include Hutchinson Guilford Syndrome, Rothmund's Syndrome, Cockayne's Syndrome, Bloom's Syndrome, and Werner's Syndrome.

Progesterone: A steroid hormone secreted by the corpus luteum of the ovary and by the placenta, that acts to prepare the uterus for implantation of the fertilized ovum, to maintain pregnancy, and to promote development of the mammary glands.

Progestin: A natural or synthetic progestational substance that mimics some or all of the actions of progesterone.

Proteome: The collection of all proteins in the body of an organism. For humans, it is estimated that there are 150,000 - 300,000 proteins, of which fewer than half have been catalogued thus far. Only about 10,000 proteins have been fully characterized to date, but systematic efforts to identify and characterize them all are now underway and could be completed before the end of this decade. Understanding their functions and interactions could take much longer.

Pulmonary emboli: A pulmonary embolus is a blood clot that breaks off from a clot in a vein (usually in the leg during a disease called thrombophlebitis) and travels throughout the heart to an artery in the lung, where it lodges. Such clots can cause serious damage to the lung and even death.

Reserve Capacity: The difference between something measured at rest versus at your maximum capacity.

Resveratrol: A compound that is found in some plants, fruits (as the mulberry), and seeds (as the peanut) and especially in the skin of grapes and certain grape-derived products (as red wine) and that has been linked to a reduced risked of coronary artery disease and cancer.

Ribonucleic acid (RNA): RNA is a sequential chain of the nucleotides Adenosine, Guanosine, Thymidine, and Uridine. In RNA, the sugar molecules are ribose. RNA is typically single stranded. The sequence of most RNA molecules is copied from specific DNA sequences by enzymes in a process called transcription.

Statin: A family of drugs (e.g. Simvastatin®, etc.) which block cholesterol production and lower blood cholesterol, used by millions of persons with high cholesterol levels.

Steroid: Fat soluble compound related to and derived from cholesterol.

Sulphorophanes: Polycyclic compounds containing sulfur-hydrogen side chains (sulfydryl groups).

Superoxide dismutase (SOD): A family of enzymes found in our cells which combines superoxide with water to form hydrogen peroxide.

Survival Function: The probability that an individual will remain alive at a particular age. The percentage of an experimental cohort that remains alive over the course of the experiment.

Tannins: A group of simple and complex phenol, polyphenol, and flavonoid compounds produced by plants. Tannins are generally protective substances. Their physiological effects vary, however, all tannins act as astringents, shrinking tissues and contracting structural proteins in the skin and mucosa.

Telomere/Telomerase: Repetitive DNA sequences at the four ends of the chromosome, which can be lengthened by an RNA-containing enzyme called telomerase. For mammals, this repeat sequence is "TTAGGG." Telomeres allow the entire functional sequence of the chromosome to be copied during cell division by providing "spare DNA" at the ends. Because the normal DNA replication process cannot be initiated at the very end of a chromosome without telomerase, chromosomes would get systematically shorter each time they were copied. Chromosomes in germ cells are passed on for unlimited numbers of generations, so that germ cells require telomerase to avoid destruction of their chromosomes and extinction of the species. Most somatic cells do not have an active telomerase, so their telomeres shorten at each cell division. When telomeres become critically shortened, the cells either die by apoptosis or cease dividing (see Hayflick Limit). Cancer cells typically develop an active telomerase enzyme as an essential ingredient of the process of becoming malignant. Therefore, a drug that blocked telomerase might function as an important anticancer therapy with very few side effects if such a drug could be identified.

Testosterone (T): The major male sex hormone, a steroid.

Thrombosis: The formation or presence of a blood clot within a blood vessel.

Transdermal Estrogen: A skin patch supplying the female hormone in a form for absorption through the skin into the bloodstream.

Translational Research: Clinical investigation with human subjects (patients or normal volunteers) in which knowledge obtained from basic research with genes, cells, or animals is translated into diagnostic or therapeutic interventions that can be applied to the treatment or prevention of disease or frailty.

Thyroid Hormone: An important hormone made by a gland in the neck which regulates the rate at which we burn our fuel (basal metabolic rate). This is synthesized linking 2 amino acids (tyrosines) and adding iodine.

Triglycerides: This is the kind of fat found in foods and in the fat cells under the skin and elsewhere. It is the body's main source of stored energy. Triglyceride circulating in the blood is thought to contribute to hardening of the arteries, but how importantly is controversial.

Zeaxanthin: A polycyclic antioxidant having a deep yellow color.