Reference conceptual framework for classifying and targeting the processes of aging; each hallmark is a potential therapeutic target.
View the study (review) →Inflammaging (chronic low-grade inflammation) accompanies aging and is bidirectionally connected to almost all the other hallmarks.
View the study (review) →Loss of proteostasis explains the accumulation of misfolded proteins in Alzheimer's, Parkinson's, and ALS.
View the study (review) →The aging markers you can explore on HealthMatrix.io, including the epigenetic clock (biological age measured by DNA methylation):
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Aging refers to the physiological, functional, and mental changes that accumulate in a biological organism over time, and the hallmarks of aging are observable biological patterns of dysfunction that occur during this process; integral to all of this is inflammaging, the chronic low-grade inflammation that accompanies aging and is bidirectionally related to almost all the other hallmarks.
Current research recognizes nine hallmarks of aging: genomic instability, telomere shortening, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication; these hallmarks increase in severity over time, but their rate of accumulation depends on genetic and environmental factors specific to each individual.
Genomic instability reflects the greater tendency of genetic mutations and chromosomal rearrangements to occur during cell division over time; the main drivers are defects in the processes that modulate cell division, such as mutations in DNA repair genes or uncorrected errors during replication, and the DNA damage response pathways that normally preserve genomic stability decline with aging.
Telomeres are protective structures at the ends of chromosomes that shorten progressively with each cell division, from about 8,000 base pairs in a newborn to 3,000 in an adult and only 1,500 in older people; when telomeres reach a critical length, the cell enters senescence or dies, and their length is profoundly influenced by the exposome, the totality of non-genetic exposures a person experiences throughout life.
Epigenetic alterations include DNA methylation and histone modification, which accumulate throughout life and contribute to the loss of proteostasis; proteostasis is the homeostatic mechanism by which the body maintains the proteome, and its loss with aging appears prominently in neurodegenerative diseases such as Alzheimer's, where misfolded proteins aggregate and drive disease progression.
Deregulated nutrient sensing affects critical pathways such as mTOR, which senses amino acid concentrations and regulates cell growth; AMPK, the master regulator of cellular energy homeostasis, whose activation declines with aging, reducing autophagy and promoting inflammation; and G protein-coupled receptors, which detect the presence of fatty acids and whose inhibition contributes to obesity.
Cellular senescence is the process by which damaged cells halt their normal cycle of growth and reproduction to prevent dysfunctional cells from proliferating; these senescent cells frequently acquire a senescence-associated secretory phenotype that is profoundly proinflammatory and immunosuppressive, and contributes directly to the inflammaging that characterizes biological aging.
Stem cell exhaustion, the loss of their capacity to divide, occurs naturally as a result of the accumulation of toxic metabolites, DNA damage, mitochondrial dysfunction, and environmental exposures; interventions such as caloric restriction, rapamycin, and certain cellular reprogramming factors can partially compensate for this exhaustion and are the subject of active longevity research.
Regular physical exercise reduces cellular senescence and increases the production of heat shock proteins that protect proteostasis; resistance and aerobic endurance exercise alter DNA methylation patterns and constitute one of the most potent interventions for slowing multiple hallmarks of aging simultaneously, including mitochondrial dysfunction, loss of muscle mass, and cognitive decline.
Heat exposure through sauna activates heat shock proteins that promote mitochondrial biogenesis and may reverse age-related mitochondrial dysfunction; caloric restriction and intermittent fasting improve nutrient sensing and activate autophagy; and supplementation with 1.5-2.5 grams of marine omega-3 has been shown to reduce oxidative stress and increase telomere length in controlled studies.
Information, not medical advice. Scientific evidence reflects the quality of the studies.