Comparative metabolomics of aging in a long-lived bat: Insights into the physiology of extreme longevity

Abstract

Vespertilionid bats (Mammalia: Order Chiroptera) live 3–10 times longer than other mammals of an equivalent body size. At present, nothing is known of how bat fecal metabolic profiles shift with age in any taxa. This study established the feasibility of using a non-invasive, fecal metabolomics approach to examine age-related differences in the fecal metabolome of young and elderly adult big brown bats (Eptesicus fuscus) as an initial investigation into using metabolomics for age determination. Samples were collected from captive, known-aged big brown bats (Eptesicus fuscus) from 1 to over 14 years of age: these two ages represent age groups separated by approximately 75% of the known natural lifespan of this taxon. Results showed 41 metabolites differentiated young (n = 22) and elderly (n = 6) Eptesicus. Significant differences in metabolites between young and elderly bats were associated with tryptophan metabolism and incomplete protein digestion. Results support further exploration of the physiological mechanisms bats employ to achieve exceptional longevity.

Emerging Insights into the Metabolic Alterations in Aging Using Metabolomics

“…This study demonstrated that glucose, fatty acid metabolism, and redox homeostasis pathways are altered with age, which leads to a decreased long-chain acylcarnitines and amino acids levels, as well as increased free fatty acid levels in the plasma of aged mice [81]. A study by Wijeyesekera et al further characterized the plasma metabolic phenotype of three long-lived murine models and identified several potential candidate biomarkers of longevity, including metabolites that were involved in phosphatidylcholine metabolism, and specific differences in the metabolic signatures of all models were also identified, suggesting the multifactorial control of the aging process [90]. De Guzman et al demonstrated that DR prevents the age-related alterations in specific metabolites involved in lipid metabolism, fatty acid metabolism, and bile acid synthesis pathways, while using global and targeted MS-based metabolomics approaches [91].…”

High basal heat-shock protein expression in bats confers resistance to cellular heat/oxidative stress

“…Additionally, most have longer lifespans than terrestrial mammals of similar body sizes, despite their high metabolic rate and its predicted consequences on oxidative metabolism. As such, they have one of the greatest disparities between body mass and longevity (Ball et al 2018 ; Bozek et al 2017 ; Davies et al 2014 ; Hughes et al 2018 ; Munshi-South and Wilkinson 2010 ; Wilkinson and Adams 2019 ). Their longevity has been attributed, at least in part, to enhanced oxidative stress resistance and protein homeostasis (Salmon et al 2009 ; Yin et al 2016 ).…”

Longitudinal comparative transcriptomics reveals unique mechanisms underlying extended healthspan in bats

“…Specifically, some wild individuals of the ~7-g Brandt's bat (Myotis brandtii) can live >41 years, over ten times longer than expected for their body size (humans live only five times longer than expected), showing little signs of ageing 6,7 . Logistically it is difficult to study bats in an ageing context, as most are only found in the wild and not easily maintained in captivity 11 . Initial longitudinal ageing studies suggest that the longest-lived genus (Myotis) maintains the length of their telomeres with age without developing cancer 12 and do not show an increased level of mitochondrial damage as expected given their metabolic rate 13 .…”