Activity of mannose-binding lectin in centenarians

Area of Science:

• Genetics
• Immunology
• Gerontology

Background:

• The MBL2 gene encodes mannose-binding lectin (MBL), crucial for innate immunity.
• MBL plays a role in pathogen recognition and complement activation.
• Cellular senescence is a hallmark of aging and is implicated in age-related diseases.

Purpose of the Study:

• To investigate the association between MBL2 gene variants and haplotypes with longevity in Italian populations.
• To explore the relationship between serum MBL levels and advanced age.
• To determine the in vitro effect of MBL on senescent human cells.

Main Methods:

• Analysis of MBL2 gene variants and haplotypes in centenarian, octo-nonagenarian, and general population cohorts from Sardinia and Campania.
• Measurement of serum MBL concentrations.
• In vitro assessment of MBL binding and effects on senescent and non-senescent human fibroblasts (IMR90).

Main Results:

• Significantly lower frequencies of high and null MBL activity haplotypes and a higher frequency of intermediate activity haplotypes were observed in centenarians and octo-nonagenarians compared to the general population.
• Centenarians and octo-nonagenarians exhibited significantly lower serum MBL concentrations.
• In vitro, MBL protein specifically bound to and lysed senescent IMR90 fibroblasts, but not other non-senescent, cycle-arrested cells.

Conclusions:

• Intermediate MBL activity haplotypes and potentially lower MBL levels may be associated with exceptional longevity.
• MBL has a novel role in the clearance of senescent cells, suggesting a protective mechanism against aging-related cellular damage.