Immunosenescence

Immunosenescence is remodelling rather than simple decline. Thymic involution begins in childhood and progresses steadily, so output of new naive T cells falls and the receptor repertoire narrows, while the memory compartment fills with oligoclonal, terminally differentiated CD28-negative cells, a process driven in most people by lifelong cytomegalovirus infection. Innate function shifts too, and a slowly rising baseline of interleukin-6 and C-reactive protein forms the inflammaging half of the picture.

Standard-dose influenza vaccine performs poorly over the age of 65, which is why higher-antigen and adjuvanted formulations exist: a large randomised trial found the high-dose trivalent vaccine roughly 24 percent more effective than standard dose at preventing laboratory-confirmed influenza in that group. The adjuvanted recombinant zoster vaccine achieved efficacy above 90 percent in people aged 70 and older, against roughly 38 percent for the earlier live attenuated vaccine in that age group.

That reframes what an intervention would have to do. The deficit is not a general shortage of immune strength but a structural loss of naive repertoire combined with a raised inflammatory baseline, and those two features want opposite treatments. Higher antigen dose and adjuvants work by compensating for a weaker response, not by rejuvenating anything.

This is the concept most heavily borrowed by anti-ageing marketing. Thymic regeneration claims rest on animal data and one small unblinded human study of a growth hormone based combination, and a rise in peripheral lymphocyte count is not evidence of restored thymic output, which requires T-cell receptor excision circle measurement or imaging. The inflammaging side is oversimplified in the other direction, since the signalling that correlates with mortality also supports responses to infection.