Volume 2 Issue 10, October 2022

The aging research field has largely focused on reversing aging-related changes in the body. However, emerging evidence about the gut microbiome indicates that it may not be optimal to just turn back the clock. Here, we advocate for a more tailored and function-focused approach promoting health across the lifespan.

A new study shows that decreased cystatin A synthesis in aged epidermis mediates age-related bone loss, whereas topical treatment that restores cystatin A mitigates this loss. This report demonstrates that skin aging has systemic consequences by showing that signals originating in skin can control bone function.

Our longitudinal study comparing the skin, gut and oral microbiomes of community-dwelling older adults and nursing home residents showed striking changes known to be linked to antibiotic resistance and disease risk. Such shifts were associated with frailty, not chronological age, and were most pronounced in the skin, the primary reservoir for infection risk.

In this Perspective, Jan Vijg and Brandon Milholland discuss that at high ages the probability of survival becomes vanishingly small, presenting a soft limit to human lifespan. They elaborate on the mechanistic basis of the observed limit to maximum human lifespan, and on the seemingly impossible future developments required to circumvent the current limit.

The intestinal microbiome has an important role in health and disease; however, the long-term effects of lifestyle choices on microbiome alterations are incompletely understood. Here, based on extensive lifestyle and medical data collected over 26 years, Si et al. demonstrate that long-term life history can predict current enterotype in older adults.

COVID-19 vaccines protect against infection, hospitalization and death in older adults, but their effectiveness is lower in this age group compared to young adults. Here, Palacios-Pedrero et al. show that age-dependent signs of immunosenescence in B and T cells in older adults correlate with poor immunological outcomes after mRNA COVID-19 vaccination but not after natural SARS-CoV-2 infection.

Skin thickness and bone density decrease with age; however, the interactions between skin and bone during aging are unclear. Here the authors show that cystatin-A is a skin-derived protein that decreases with age and causes age-related bone loss. Further, topical application of calcipotriol stimulates cystatin-A production in the skin and alleviates bone loss.

Splicing dysfunction has been observed in Alzheimer’s disease but it remains unclear whether splicing defects have a causal role. Here the authors generate a mouse model with perturbed U1 snRNP activity, recapitulating RNA splicing defects, neuron hyperexcitability, neurodegeneration and synergy with the amyloid cascade when crossed with 5xFAD mice.

A metagenomic study of gut, oral and skin microbiota describes a pattern of microbial dysbiosis in more frail institutionalized older adults and identifies the skin as the major reservoir of pathogenicity.

Immune system dysfunction has been implicated in the development of dementias, but its causal role remains unknown. Providing converging results from different lines of human research, this study by Lindbohm et al. suggests that autoimmunity may be a modifiable component in diseases causing dementia.