Healthspan and lifespan research are two distinct but interconnected areas in aging studies. Lifespan research aims to extend the total number of years an individual lives, seeking interventions that can delay the onset of age-related diseases and prolong life itself. In contrast, healthspan research prioritizes the quality of those years, concentrating on extending the period of life spent in good health and free from chronic diseases or disabilities. While lifespan research might focus on genetic and biomedical advancements to increase longevity, healthspan research emphasizes lifestyle changes, preventative medicine, and treatments that improve physical and mental well-being.
Last week, an exciting study by researchers at Duke-NUS Medical School demonstrated that the inhibition of IL-11 signaling extends the healthspan and lifespan of mice via a neutralizing IL-11 antibody (X203) drug. IL-11 was not previously thought to be important for ageing, but SNPs at the IL11 locus are associated with osteoarthritis and menopause, and IL-11 is linked with senescence and diseases that are common in older people. The team’s results suggest that anti-IL-11 therapy, which has a reassuring safety profile and is currently in early-stage clinical trials for fibroinflammatory diseases, is a potentially translatable approach for extending human healthspan and lifespan.
DOI:10.1038/s41586-024-07701-9
An earlier paper also showed the potential of antibody drugs in rejuvenating an aging immune system. A team from Stanford University School of Medicine showed that a one-time antibody treatment can deplete myeloid-biased haematopoietic stem cells, thus restoring characteristic features of a more youthful immune system, including increasing common lymphocyte progenitors, naive T cells and B cells, while decreasing age-related markers of immune decline. Depletion of my-HSCs in aged mice improves primary and secondary adaptive immune responses to viral infection. These findings may have relevance to the understanding and intervention of diseases exacerbated or caused by dominance of the haematopoietic system by my-HSCs.
On the other hand, antibodies themselves can be an aging factor that drives adipose tissue fibrosis and metabolic decline. A paper by scientists at Columbia University discovered that IgG accumulates in adipose tissue during aging and is reduced by caloric restriction. IgG activates macrophages to induce adipose tissue fibrosis. Preventing IgG accumulation in aging prolongs healthspan and lifespan, and targeting the IgG recycling receptor FcRn rejuvenates metabolic health in aged mice.
