Editorial: Molecular crosstalk between endocrine factors, paracrine signals, and the immune system during aging

Editorial: Molecular crosstalk

between endocrine factors,

paracrine signals, and the

immune system during aging

Durai Sellegounder

, Luigi Ferrucci

, Rajakumar Anbazhagan

and Nathan Basisty

Buck Institute for Research on Aging, Novato, CA, United States,

Translational Gerontology Branch,

National Institute on Aging, National Institutes of Health, Bethesda, MD, United States,

Eunice

Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of

Health, Bethesda, MD, United States

KEYWORDS

aging, endocrinology, immune system, paracrine signal, metabolism & endocrinology,

hormones, senescence

Editorial on the Research Topic

Molecular crosstalk between endocrine factors, paracrine signals, and

the immune system during aging

Introduction

Aging is a complex biological process that gradually declines physiological function and

increases susceptibility to disease. Various factors, including genetics, lifestyle, and

environmental factors, inﬂuence this process (1). One key factor that has emerged as a

signiﬁcant contributor to aging is the interactions between the endocrine, paracrine, and

immune systems. The endocrine and immune systems are closely interconnected and work

together to maintain homeostasis in the body. Hormones produced by the endocrine

system, such as insulin, growth hormone, prolactin, and thyroid hormone, have a

signiﬁcant effect on the immune system. For example, Insulin increases production of

inﬂammatory cytokines like IL-6 during LPS stimulation in macrophages (2). Conversely,

immune cells, such as T and B cells, and senescent cells, can produce hormones that

regulate immune function and interact with the endocrine system. For example, senescent

cells, via the senescence-associated secretory phenotype (SASP), release growth factors and

cytokines that interact with the local and systemic environment (3, 4). The endocrine and

immune systems utilize paracrine signaling to coordinate cellular responses to any stress in

distant tissues in the body. There is a signiﬁcant gap in the ﬁeld regarding our

understanding of the interaction between these pathways during aging and

diseased conditions.

The current Research Topic, “Molecular Crosstalk Between Endocrine Factors,

Paracrine Signals, and the Immune System During Aging,” helps to bridge this gap by

highlighting recent research ﬁndings at the intersection of endocrine-immune axis, aging,

and age-related pathologies, as well as opportunities for therapeutic interventions.

Frontiers in Endocrinology frontiersin.org01

OPEN ACCESS

EDITED AND REVIEWED BY

Antonello Lorenzini,

University of Bologna, Italy

*CORRESPONDENCE

Durai Sellegounder

[email protected]

SPECIALTY SECTION

This article was submitted to

Endocrinology of Aging,

a section of the journal

Frontiers in Endocrinology

RECEIVED 11 April 2023

ACCEPTED 14 April 2023

PUBLISHED 21 April 2023

CITATION

Sellegounder D, Ferrucci L, Anbazhagan R

and

Basisty N (2023) Editorial:

Molecular crosstalk between

endocrine factors, paracrine signals,

and the immune system during aging.

Front. Endocrinol. 14:1203755.

doi: 10.3389/fendo.2023.1203755

and Basisty. This is an open-access article

distributed under the terms of the Creative

Commons Attribution License (CC BY). The

use, distribution or reproduction in other

forums is permitted, provided the original

author(s) and the copyright owner(s) are

credited and that the original publication in

this journal is cited, in accordance with

accepted academic practice. No use,

distribution or reproduction is permitted

which does not comply with these terms.

TYPE Editorial

PUBLISHED 21 April 2023

DOI 10.3389/fendo.2023.1203755

Highlights of manuscripts in this

research topic

Endocrine f actors regulate many physiological processes,

including growth and development, metabolism, and reproduction.

With age, the levels of many endocrine factors change, leading to

alterations in these processes. For example, insulin receptor (InsR)

signaling is a well-conserved pathway regulating longevity. Makhijani

et al. reviewed the function of InsR signaling pathways in different

immune cell subsets and their impact on cellular metabolism,

differentiation, and effector versus regulatory function. With ample

evidence from the literature, the authors provided mechanistic links

between altered InsR signaling and immune dysfunction in various

disease settings and conditions, focusing on age-related conditions,

such as type 2 diabetes and cancer.

The immune system plays a key role in defending the body

against infection and disease. As we age, the immune system

undergoes signiﬁcant changes, including a decline in the

production of new immune cells and a decrease in the ability of

immune cells to respond to infection. The reduction in immune cells

can lead to an increased susceptibility to infections and a reduced

ability to clear infections once they occur. King et al. provided a brief

report on the relationship between aging, reproductive health, and

immune function. From the studies in the lab, the authors claim that

transplanting young ovaries into old mice increased healthspan and

lifespan. However, the results from Mason’s lab suggest that the

protective effect of the ovarian transplant was not due to hormonal

activity, as hormone-depleted ovaries from young mice also extended

their lifespan. The authors claim that additional factors other than

ovarian hormones are the reason for health beneﬁts. In their current

report, the authors speciﬁcally focused on the inﬂuence of young

ovarian tissues on immune function in post-reproductive female mice

in the presence or absence of ovarian follicles.

Hormones play an essential role in the immune system and can

signiﬁcantly impact the development and progression of rheumatic

disorders. Bertoldo et al. reviewed the interaction between the

endocrine hormones and the immune system from the perspective

of rheumatic disorders. The review article covers recent data

describing the role of bone-related hormones and cytokines.

The pituitary gland produces growth hormone (GH), which

plays a key role in growth and development during childhood and

adolescence. While some studies have suggested that GH

replacement therapy may improve markers of health and

longevity in older adults, other studies have raised concerns about

GH treatment’s potential risks and side effects, such as an increased

risk of cancer and diabetes. As a part of this Research Topic, Bartke

reviewed the relationship between growth hormones and longevity.

He suggested that a slower pace of life is associated with extended

longevity within and between species. This review warrants future

studies in u nderstanding energy metabolism and nutrient-

dependent signaling at different stages of life.

Paracrine signals are molecules produced by one cell and act on

neighboring cells to regulate their function. These signals are vital in

maintaining tissue homeostasis and responding to damage or

injury. In aging, the production and response to paracrine signals

can become dysregulated, leading to tissue dysfunction and disease.

For example, senescent cells’ production of inﬂammatory cytokines

can lead to chronic inﬂammation, a hallmark of aging, and

associated with man y age-related diseases. Kuehneman n et al.

reported a new senescence-associated secretory phenotype

marker. Nicotinamide Phosphoribosyl Transferase (NAMPT), the

enzyme involved in the rate-limiting step of NAD biosynthesis, is

increased in senescent cells. Results from the research show that the

senescence cells displayed increased NAMPT, which is different

from classical DNA damage response and without further increase

in NAD. Based on the observed results, the authors believe that

increased extracellular NAMPT (eNAMPT) during senescence is

another SASP marker that could regulate metabolic functions in

distant cells. Further, the authors showed that diabetic mice

displayed elevated levels of eN AMPT, and treatment with the

senolytic drug ABT-263 can rescue the high levels of eNAMPT.

Conclusion and future perspective

In conclusion, the crosstalk between endocrine factors,

paracrine signals, and the immune system is a complex and

dynamic process that plays a crucial role in aging. The interaction

between these vital pathways has important implications for aging

research and interventions. For example, targeting endocrine

factors such as growth hormone and IGF-1 or paracrine signals

such as inﬂammatory cytokines may provide new therapeutic

strategies to improve immune function in the elderly population.

The review articles and research manuscripts presented in this

Research Topic have highlighted this crosstalk ’s importance and

identiﬁed new intervention targets. Further research is needed to

fully un derstand the d ynamic interaction s be tween biological

pathways and develop effective interventions to improve health

and prevent age-related diseases.

Author contributions

All authors listed have made a substantial, direct, and intellectual

contribution to the work and approved it for publication.

Funding

This work was supported by the National Institutes of Health

(NIH) and the Intramural Research Program, National Institute on

Aging (NIA). This work was supported by a grant from the National

Institutes of Health (NIH)/National Institute on Aging (NIA) U54

AG079779 (PI: Elisseeff). Funding was also provided from an

Impetus Longevity Grant (PI: Basisty).

Conﬂict of interest

The authors declare that the research was conducted in the

absence of any commercial or ﬁnancial relationships that could be

construed as a potential conﬂict of interest.

Sellegounder et al. 10.3389/fendo.2023.1203755

Frontiers in Endocrinology frontiersin.org02

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Sellegounder et al. 10.3389/fendo.2023.1203755

Frontiers in Endocrinology frontiersin.org03