A measurable substance in an organism that is indicative of some phenomenon such as disease, infection, or environmental exposure.

A gene encoding a transcription factor (CLOCK) that affects both the persistence and period of circadian rhythms. CLOCK functions as an essential activator of downstream elements in the pathway critical to the generation of circadian rhythms. In humans, polymorphisms in the CLOCK gene have been associated with increased insomnia, weight loss difficulty, and recurrence of major depressive episodes in patients with bipolar disorder.

A biomarker of aging based on alterations in an organism’s DNA methylation (DNAm) profile. Methylations occur naturally and regulate gene expression. With age, the methylation state of a gene may change. These changes are quantifiable, serving as a means to gauge biological age, which is often different from chronological age. Several variations of epigenetic clocks have been identified. They are generally categorized according to the type and number of tissues used to formulate the calculation, as well as the type of age measured (e.g., epigenetic versus phenotypic). The most widely used clocks include: - HorvathAge, which predicts intrinsic epigenetic age acceleration, a phenomenon in which an organism's aging is influenced by internal physiological factors such as normal metabolism and genetics.^[1] - DNAm PhenoAge, which predicts time-to-death among people of the same chronological age, based on biomarkers of age-related disease.^[2] - DNAm GrimAge, which predicts lifespan and healthspan, based on DNAm surrogates in blood, including biomarkers of aging and alterations in blood composition.^[3]

The gradual deterioration of the immune system brought on by natural age advancement. Immunosenescence is considered the most important reason for the increased rate of infections (and cancers) in older adults and is believed to be the diminished or exhausted function of the immune system that naturally occurs with aging.

A biochemical process involving the addition or subtraction of a methyl group (CH3) to another chemical group. In epigenetics, a methyl group is added to an amino acid in a histone tail on DNA, altering the activity of the DNA segment without changing its sequence. Under- and over-methylation are referred to as hypomethylation and hypermethylation, respectively.

Senescence is a response to stress in which damaged cells suspend normal growth and metabolism. While senescence is vital for embryonic development, wound healing, and cancer immunity, accumulation of senescent cells causes increases inflammation and participates in the phenotype of aging.

Distinctive structures comprised of short, repetitive sequences of DNA located on the ends of chromosomes. Telomeres form a protective “cap” – a sort of disposable buffer that gradually shortens with age – that prevents chromosomes from losing genes or sticking to other chromosomes during cell division. When the telomeres on a cell’s chromosomes get too short, the chromosome reaches a “critical length,” and the cell stops dividing (senescence) or dies (apoptosis). Telomeres are replenished by the enzyme telomerase, a reverse transcriptase.