Recent work has linked psychological stress with premature cellular aging as indexed by reduced leukocyte telomere length. The combination of shorter telomeres with high telomerase activity (TA) may be indicative of active cell stress. We hypothesized that older individuals characterized by shorter telomeres with high TA in unstimulated leukocytes would show signs of high allostatic load and low levels of protective psychosocial resources. We studied 333 healthy men and women aged 54-76 y who underwent laboratory testing in which we measured cardiovascular, neuroendocrine, and inflammatory responses to standardized mental stress tasks. The tasks elicited prompt increases in blood pressure (BP), heart rate, cortisol, and mediators of inflammation and reductions in heart rate variability, returning toward baseline levels following stress. However, men having shorter telomeres with high TA showed blunted poststress recovery in systolic BP, heart rate variability, and monocyte chemoattractant protein-1, together with reduced responsivity in diastolic BP, heart rate, and cortisol, in comparison to men with longer telomeres or men with shorter telomeres and low TA. Shorter telomeres with high TA were also associated with reduced social support, lower optimism, higher hostility, and greater early life adversity. These effects were independent of age, socioeconomic status, and body mass index. We did not observe differences among older women. Our findings suggest that active cell stress is associated with impaired physiological stress responses and impoverished psychosocial resources, reflecting an integration of cellular, systemic, and psychological stress processes potentially relevant to health in older men. cellular senescence | allostasis | psychological distress T elomeres are nucleoprotein structures composed of tandem hexanucleotide repeats of the sequence TTAGGG that cap the ends of eukaryotic chromosomes, protecting them from end-to-end fusion and degradation during cell division. Human telomeric DNA naturally shortens with age during somatic cell divisions and as a result of oxidative attack (1, 2). At critical shortness, telomeres exhibit impaired function, leading to genomic instability, apoptosis, and cell senescence, often with altered transcriptional programming and mitochondrial dysfunction (1). Telomere attrition represents one of the hallmarks of aging (3). In humans, Mendelian singlegene mutations that directly compromise telomere maintenance cause premature mortality and onset of a spectrum of diseases overlapping with the age-related diseases common in the population (4). In addition, genome-wide association studies show that certain combinations of SNPs at genetic loci encoding known telomere-maintenance factors are associated with increased relative risks for pulmonary and coronary diseases (5). Shorter telomere length (TL) in white blood cells is linked and, in some cases, anticipates aging-related morbidity and mortality from conditions with immune system involvement, such as infectious disease...