Immune Aging is the Foundation of Frailty
Here find a perspective on the great importance of a functional immune system to health in later life. Many of the declines of aging appear strongly influenced, at the very least, by the progressive disarray of the immune system. It becomes less competent in destroying pathogens and malfunctioning cells, but at the same time ever more active in response to the molecular damage and cellular dysfunction accompanying aging. That inappropriate activity takes the form of chronic inflammation that disrupts tissue function and accelerates the onset and progression of all of the common age-related conditions.
The interrelation of the processes of immunity and senescence now receives an unprecedented emphasis during the COVID-19 pandemic, which brings to the fore the critical need to combat immunosenescence and improve the immune function and resilience of older persons. Here we review the historical origins and the current state of the science of innate and adaptive immunity in aging and longevity. Following a century of study, at the present time, natural immunity is understood to consist of three interrelated parts: physiological barriers, innate immunity, and adaptive immunity. All of these are affected by aging. Immunosenescence results in increased susceptibility and severity of infectious diseases and non-communicable age-associated diseases, among them cancer, cardiovascular disease, and autoimmunity.
Excessive levels or activity of antimicrobial peptides, C-reactive protein, complement system, TLR/NF-κB, cGAS/STING/IFN and AGEs/RAGE pathways, myeloid cells and NLRP3 inflammasome, declined levels of NK cells in innate immunity, thymus involution and decreased amount of naive T-cells in adaptive immunity, are biomarkers of aging and predisposition factors for cellular senescence and aging-related pathologies. Long-living species, human centenarians, and women are characterized by less inflammaging and decelerated immunosenescence. Despite recent progress in understanding, a harmonious theory of immunosenescence is still developing. Geroprotectors targeting these mechanisms are just emerging, including rapamycin, senolytics, metformin, acarbose, spermidine, NAD+ enhancers, and lithium.