It’s a fact of life: Some people age better than others. Some ease into their 90s with mind and body intact, while others battle diabetes, Alzheimer’s or mobility issues decades earlier. Some can withstand a bad fall or bout of the flu with ease, while others never leave the hospital again.

New University of Colorado Boulder-led research, published in Nature Genetics, sheds light on why that is.

In it, an international team of co-authors identifies more than 400 genes associated with accelerated aging across seven different sub-types. The study reveals that different groups of genes underlie different kinds of disordered aging, a.k.a. frailty, ranging from cognitive decline to mobility issues to social isolation.

With the intensification of global aging, the incidence of age-related diseases (including cardiovascular, neurodegenerative, and musculoskeletal disorders) has been on the rise, and cellular senescence is identified as the core driving mechanism. Cellular senescence is characterized by irreversible cell cycle arrest, which is caused by telomere shortening, imbalance in DNA damage repair, and mitochondrial dysfunction, accompanied by the activation of the senescence-associated secretory phenotype (SASP). In this situation, proinflammatory factors and matrix-degrading enzymes can be released, thereby disrupting tissue homeostasis. This disruption of tissue homeostasis induced by cellular senescence manifests as characteristic pathogenic mechanisms in distinct disease contexts. In cardiovascular diseases, senescence of cardiomyocytes and endothelial cells can exacerbate cardiac remodeling.