DNA methylation clocks struggle to distinguish inflammaging from healthy aging, but feature rectification improves coherence and enhances detection of inflammaging.

Unlabelled: Biological age estimation from DNA methylation and determination of relevant biomarkers is an active research problem which has predominantly been tackled with black-box penalized regression. Machine learning is used to select a small subset of features from hundreds of thousands CpG probes and to increase generalizability typically lacking with ordinary least-squares regression. Here, we show that such feature selection lacks biological interpretability and relevance in the clocks of the first- and next-generations, and clarify the logic by which these clocks systematically exclude biomarkers of aging and disease.

Small-animal blood exchange is an emerging approach for systemic aging research.

We describe a small-animal blood exchange approach developed for aging research as an alternative to heterochronic parabiosis or plasma injections. In parabiosis, animals are surgically coupled, which has several disadvantages, including difficulty controlling experimental procedure, the effects of shared organs, environmental enrichment from jointly exploring the housing enclosure, involuntary exercise and an imprecise onset of blood sharing. Likewise, in plasma injections, the added volumes need to be small, and there is little flexibility in changing the relative contributions of ectopic to endogenous blood components.

Plasma dilution improves cognition and attenuates neuroinflammation in old mice.

Our recent study has established that young blood factors are not causal, nor necessary, for the systemic rejuvenation of mammalian tissues. Instead, a procedure referred to as neutral blood exchange (NBE) that resets signaling milieu to a pro-regenerative state through dilution of old plasma, enhanced the health and repair of the muscle and liver, and promoted better hippocampal neurogenesis in 2-year-old mice (Mehdipour et al., Aging 12:8790-8819, 2020).

Skeletal muscle as an experimental model of choice to study tissue aging and rejuvenation.

Skeletal muscle is among the most age-sensitive tissues in mammal organisms. Significant changes in its resident stem cells (i.e.