Sex and gender affect immune aging

Abstract

The proposed review aims to elucidate the intricate interplay between biological factors (sex differences) and socially constructed factors (gender differences) in the context of immune aging. While the influence of biological differences between men and women on various aspects of immune responses has long been recognized, it is crucial to acknowledge that gender, encompassing the social and cultural roles and expectations associated with being male or female, also significantly shapes these processes. Gender can either accelerate immune aging or promote longevity. By recognizing the impact of both biological and social factors, this work seeks to offer a comprehensive understanding of why men and women may experience divergent trajectories in immune aging and varying outcomes in terms of longevity. Discrepancies in perceived roles of the sexes, both within families and at work, contribute to differing patterns of antigen exposure. Additionally, variations in micronutrient intake and access to preventive healthcare facilities may exist. Health promotion knowledge often correlates with educational attainment, which is unequally represented between males and females in many cultures and across generations in the Western world. In countries without a universal healthcare system, access to healthcare relies on family prioritization strategies to cope with economic constraints, potentially limiting access to specific treatments and affecting immune responses negatively. As a result, both biological factors and social and behavioral factors associated with gender contribute to disparities in immune responses, susceptibility to infections, autoimmune diseases, and vaccine responses among older individuals. However, as demonstrated by the COVID-19 pandemic, older females exhibit greater resilience to infections than older males. Given the crucial role of the immune system in achieving longevity, it is not surprising that women live longer than men, and the number of female centenarians surpasses that of male centenarians.

Centenarians, semi and supercentenarians, COVID-19 and Spanish flu: a serological assessment to gain insight into the resilience of older centenarians to COVID-19

“…Coming back to COVID-19 older people mortality, there are conflicting findings in the literature [ 7 ]. However, this quoted review revealed the following: (a) Consistent with evidence indicating that women tend to outlive men even during severe famines and epidemics, women exhibit greater resilience [ 8 ], although conflicting data exist regarding female centenarians in Northern Italy [ 9 ]; (b) Due to their frailty [ 10 ], centenarians, on the whole, generally succumb to COVID-19 at rates similar to or greater than other older individuals [ 11 – 13 ], with the exception of Japan, where their numbers continued to rise due to general precautions against viral infections, such as social distancing [ 14 ]; (c) During the initial wave of the pandemic in 2020, before introduction of vaccines, “older” centenarians (> 101 years old) exhibited greater resilience to COVID-19 than “younger” ones (< 102 years old) [ 11 , 15 ].…”

“…Moreover, the disease is more severe and lethal in men than in women [ 3 , 7 ]. The degree of immune-inflammatory responses differs between men and women and persists throughout life [ 7 , 8 , 45 ]. Besides sex hormones, sex chromosomes play a role, as several immune genes are found on the X chromosomes.…”

“…X-chromosome inactivation silences one X chromosome in the majority of XX cells, equalizing the expression of X-linked genes to that in XY cells. However, not all genes are silenced; those that evade X inactivation are believed to play a role in certain immune responses [ 8 , 46 ] Generally, women have a stronger adaptive immune response (especially humoral), while men have a stronger natural immune response, i.e., an inflammatory one [ 7 , 8 , 45 , 47 ]. Excess mortality observed in 27 European countries during the winter circulation of respiratory pathogens from 2016 to 2020 was higher in males compared to females.…”

Human in vivo evidence of associations between herpes simplex virus and cerebral amyloid-beta load in normal aging

“…To minimize this limitation, we only reported results that survived multiple comparisons, showed effect sizes above the minimum established, and were further supported by Bayesian evidence. Moreover, the study sample has twice more females than males, which may impact results given the unquestionable role of gender in the development and outcomes of immune responses [ 64 , 65 ]. Indeed, 80% of autoimmune diseases occur in women, who typically show stronger immune responses than males.…”

Serological Antibodies against Kidney, Liver, and Spleen Membrane Antigens as Potential Biomarkers in Patients with Immune Disorders

“…Sex and age are two key factors that have been linked to the development of reactive antibodies in certain autoimmune diseases. Many autoimmune conditions like SLE, SjS, and type 1 diabetes exhibit a higher prevalence in females compared to males [26][27][28][29]. On the contrary, it has been observed that men with SLE more frequently suffer from renal impairments such as LN and face a heightened risk of progressing to end-stage renal disease, although there is some uncertainty surrounding this question [27,30,31].…”