Telomere shortening has been associated with several age-related diseases, in addition to being considered a hallmark of aging. Frailty is a clinical syndrome characterized by an accentuated physiological and functional decline that might be a predictor of an adverse condition in older age. The present study evaluated the relationship between frailty and telomere shortening in older adults from Mexico City, Mexico. This was a cross-sectional study. Data were collected from 323 frail older adults, including physical and environmental factors, such as body mass index, comorbidities, physical activity and tobacco consumption. Telomere length was measured by real-time polymerase chain reaction. The frailty syndrome was diagnosed using the Fried criteria. An association between frailty and telomere shortening was found in both sexes. Telomere length decreased from 6.05 kb (5.54-6.48 kb) to 4.20 kb (3.80-4.54 kb; P