Autophagy flux varies by sex and cell type during human aging
In older adults, higher autophagy flux in blood cells linked to lower physical function and decreased after a 12-week exercise intervention.
Researchers analyzed transcriptomics and autophagic flux across matched human cells, including primary fibroblasts, induced neurons, and peripheral blood mononuclear cells from a healthy aging cohort. Autophagy-related gene expression rose with age in fibroblasts and induced neurons. However, functional autophagy flux did not match transcription and varied by sex and cell type. Flux declined in male fibroblasts, remained stable in female fibroblasts, and rose in female induced neurons. In blood mononuclear cells, flux grew more heterogeneous with age and trended higher in older people. Among participants over 70 years old, higher autophagic flux correlated with poorer physical function. Finally, a 12-week mild exercise pilot study lowered blood cell autophagy flux alongside improved physical function.
Why it matters
These findings challenge the common view that autophagy universally declines with age across all tissues. Instead, higher autophagy flux in late life may reflect a compensatory reaction to age-related stress rather than preserved functional capacity.
Caveats
The functional connections between autophagy flux and late-life physical decline are observational, and the exercise trial was a small pilot study.
The paper
Autophagy Flux Is Remodeled Sex- and Cell Type-Specifically During Human Aging, and Is Linked to Reduced Physical Function in Older Adults
Moreno TM, Heimler SR, Moran RJ et al.
Aging Cell · 28 Sep 2026