# Blood Cell Mitochondrial Respiration Increases With Age and Varies by Sex in Healthy Adults

## TL;DR

This study shows that mitochondrial respiration in blood cells increases with age and differs between men and women in healthy adults.

## Contribution

The study reveals sex-specific and age-related changes in mitochondrial respiration in blood cells from healthy adults.

## Key findings

- Chronological age is positively associated with maximal respiration in PBMCs and lymphocytes.
- Age-related increases in platelet respiration are observed only in men, while PBMC respiration increases only in women.
- Glycolysis and respiration are strongly linked in platelets, PBMCs, and monocytes but not in lymphocytes.

## Abstract

Mitochondrial dysfunction is recognized as a biological hallmark of aging; however, bioenergetic capacity across the healthy human life course remains insufficiently characterized. While aging is generally associated with a systemic decline in mitochondrial function (“age‐related bioenergetic decline”), recent research suggests that age‐related bioenergetic differences are context dependent. Blood cells are extensively utilized as accessible samples for human bioenergetic profiling; therefore, our goal was to characterize bioenergetic capacity in platelets, peripheral blood mononuclear cells (PBMCs), monocytes, and lymphocytes of healthy adults from the San Diego Nathan Shock Center Clinical Cohort representative of the adult life course (20–80+ years of age). In our sample of 72 adults, we found that chronological age was positively associated with PBMC (maximal respiration [Max] β = 0.147, p = 0.028) and lymphocyte respiratory capacity (Max β = 0.135, p = 0.041). Notably, the pattern of age‐related differences varied by sex; age showed a weak positive association with platelet respiration (Max β = 0.219, p = 0.037) in men but not in women. Similarly, age showed a strong positive association with PBMC respiration (Max β = 0.206, p = 0.018) in women but not in men. We also explored the relationship between glycolysis and respiration and found strong positive associations in platelets, PBMCs, and monocytes, but not lymphocytes. It is possible that, despite our cohort consisting of healthy, disease‐free individuals, the elevated respiratory capacity in older adults may be reflective of compensatory mechanisms that require further investigation. Nonetheless, these findings underscore the importance of considering biological context, such as donor health, sex, and tissue type, in understanding age‐related bioenergetic differences.

Using samples from the San Diego Nathan Shock Center Clinical Cohort, we found that blood cell bioenergetic capacity is generally positively associated with age and sex dependent. These findings highlight the importance of biological context in bioenergetics research. Created in BioRender. Lab, M. (2025) https://BioRender.com/pvgt48f.