Obesity as a Factor of Frailty in the Elderly Volume 60- Issue 4

Scarantino ER*

• Geriatric resident at AOU Careggi, Florence, University of Florence, Italy

Received: February 08, 2025; Published: February 20, 2025

*Corresponding author: Scarantino ER, Geriatric resident at AOU Careggi, Florence, University of Florence, Italy

DOI: 10.26717/BJSTR.2025.60.009479

Abstract PDF

Objective of the study: to collect and analyze literature data on the role of obesity and visceral adipose tissue as a riskfactors for frailty in elders and understand the biological mechanism of this possible connection.
Materials and Methods: studies, systematic review and meta-analysis of literature data.
Results and conclusions: real pathophysiological correlation between frailty and obesity exist; meta-analysis show that some anthropometric measures could be useful tools to predict the risk of frailty but more studies are necessary to apply them to clinical practice.

Keywords: Frailty; Visceral Adipose Tissue; Elder People; Inflammation; Body Mass Index; Waist Circumference; Cytokines; Meta-Analysis

Abbreviations: BMI: Body Mass Index; WC: Waist Circumference; Bia: Bioimpetizometry; EVFA: Estimated Visceral Fat Area Interleukin-6 (Il-6); TNF: Tumour Necrosis Factor Insulinlike Growth Factor 1 (Igf1)

Frailty is a clinically identifiable state of diminished physiological reserve and increased vulnerability to a broad range of adverse health outcomes, becoming more common as population age. Despite the existence of various definitions, the most complete and interesting is Fried’s “frailty phenotype”: clinical syndrome resulting from altered metabolism coupled with abnormal stress responses. It’s like like a non-harmonious symphony between altered systems: metabolic one (glucose intolerance, insulin resistance), musculoskeletal (energy utilization and production by mitochondria), and stress-response system (autonomic nervous system dysregulation and hypothalamic- pituitary adrenal axis dysregulation) [1]. First manifestation of frailty is weakness, followed by slowness, physical inactivity, and, at last, weight loss [2]. The underlying biological mechanism of frailty is complex and in continuous study: the main important factors are cellular senescence, mitochondrial dysfunction, deregulated nutrient sensing, hormonal changes and chronic inflammation [3,4]. This last one has been the object of numerous studies and it has been found that one of the most pro inflammatory tissues is adipose tissue especially the visceral one [5]. In the following pages I’ll explain its metabolic function. Additionally increased adiposity is linked to higher depression rates, cognitive decline [6] and osteoporosis [7] in older individuals. All these reasons have been also proposed to mediate the pathway to frailty. Another important consideration to do is weakness as the first manifestation of frailty; in elders it’s quite typical to lose muscle mass and strength. This process it’s called “sarcopenia” and one of the possible causes is once again adipose tissue, in fact last articles in literature start to talk about “sarcopenic obesity” in seniors [5]

In conclusion, some studies have investigated whether obesity identification tools can predict the risk of frailty [8]; the following pages contain some interesting work on this possible role.

to write this article I relied on systematic reviews and meta-analysis in literature about the link between obesity and frailty status in seniors. I found some interesting analysis and cross-sectional studies about obesity indicator tools like anthropometric measures (BMI and WC) and body composition’s values by BIA (eVFA) as predictors of frailty [8,9]

From the material in the literature, I believe the best example to understand the role of fat in frailty is that of sarcopenic obesity (Figure 1) [5]. Visceral adipose tissue is a metabolically active tissue and it has number of inflammatory pathways in common to muscle; it secretes cytokines such as adiponectin, IL-6 and TNF activating macrophages, mast cells and T lymphocytes, and promoting a continuous low-level inflammation. [10-12]. This state leads to insulin resistance and reduction in the anabolic actions of IGF1, reducing muscle protein synthesis and promoting gain in fat mass and loss of muscle mass by exacerbating sarcopenia [13-14]. Also Obesity induces Leptin resistance, reducing muscle fatty oxidation and ectopic fat deposition in skeletal muscles [15,16]. Intramyocellular lipids induce dedifferentiation of mesenchymal adipocyte-like progenitor cells that express fatty tissue genes [17]. In this way regeneration potential of muscle is impaired, which might promote fibrosis, thereby promoting insulin resistance [18-19] like a feedforward cycle. In addition another important factor in sarcopenic obesity is precisely aging, promoting insulin resistance and thus accumulation of adipose tissue and sarcopenia, reducing hormones and protein synthesis [5].

Increased overall adiposity is also linked to higher depression rates, cognitive decline [6] and osteoporosis [7], due to the constant inflammation state and altered hormone secretion, impacting on health and functional abilities of elderly individuals. Lots of studies demonstrate that both obesity and a large waist circumference (WC) were associated with systemic inflammation and insulin resistance, therefore with frailty [20]. While BMI is the most widely used tool to estimate obesity, the optimal level of adiposity in older adults is still a matter of discussion. BMI doesn’t distinguish between muscle mass or fat mass. Additionally in elderly vertebral compression results in a reduction in height [21] which affects anthropometric measures such as BMI. In some reviews and meta-analysis it is demonstrated that BMI over > 29.9 is associated with high risk of frailty, but also a BMI under 18.5 represents a risk for it. The relationship between BMI and the risk of frailty highlights a non-linear association with U-shape with a nadir of risk at a BMI of 18.5–29.9 kg/m2. [8]. In fact weight loss is the last step of Fried Frailty phenotype, and manifests a state of denutrition and illness like cachexia WC is a better tool to indicate regional distribution of fat especially in seniors, even if it can’t distinguish between visceral adipose tissue and subcutaneous one [22]. In some meta-analysis adults with abdominal obesity have a significantly higher risk of frailty [8,23], in others is necessary both high BMI and WC to denote frailty risk [24]; in some cross sectional studies high WC is associated with lower MMSE scores in both genders but is significant only in males with normal BMI and WC [25].Other interesting studies suggest the use of BIA to find a correlation between adipose tissue and frailty even if is unusual tool of obesity measurement in daily clinical practice; in a cross sectional study estimated visceral fat area (eVFA) calculated by BIA is more predictive of frailty than WC or BMI and remain associated with an increased risk of frailty even after adjustments for multiple variables such as age, WC, chronic conditions, and glucose and lipid metabolism [9].

There is a pathophysiologic link between obesity and frailty, especially due to the role of visceral adipose tissue. Some systematic review and meta-analysis demonstrate that some obesity measurement tools could be used in practical clinics to predict frailty. Even more studies are necessary because there are some confounding factors like gender and comorbid conditions that could affect the relationship between BMI or WC and frailty. In addition the studies in literature were very heterogeneous and the exam by review was not easy [8,9] The use of BIA is not very common in daily clinical practice, but it seems a more direct and reliable measure than anthropometric measurements, but the study proposing this view is cross sectional and the associations observed could not establish a causal relationship between visceral fat obesity and frailty. Therefore, further longitudinal studies are required [24] Understanding the mechanism above, some effective interventions could be implemented to reduce risk of frailty like, protein intake, caloric restriction and regular aerobic exercise [5,25-27].

1. Fried LP, Cohen AA, Xue QL, Walston, J, Bandeen Roche K, et al. (2021) The physical frailty syndrome as a transition from homeostatic symphony to cacophony. Nat Aging 1: 36-46.
2. Stenholm S, Ferrucci L, Vahtera J, Emiel O Hoogendijk, Martijn Huisman, et al. (2019) Natural course of frailty components in people who develop frailty syndrome: evidence from two cohort studies. J Gerontol. A Biol Sci Med Sci 74: 667-674.
3. Kennedy BK, Berger SL, Brunet A, et al. (2014) Geroscience: linking aging to chronic disease. Cell 159: 709-713.
4. López Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2023) Hallmarks of aging: an expanding universe. Cell 186: 243-278.
5. Batsis JA, Villareal DT (2018) Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies. Nat Rev Endocrinol 14(9): 513-537.
6. Sakakura K, Hoshide S, Ishikawa J, Shin ichi Momomura, Masanobu Kawakami, et al. (2018) Association of body mass index with cognitive function in elderly hypertensive Japanese. Am J Hypertens 21: 627-632.
7. Felson DT, Zhang YQ, Hannan MT, J J Anderson (1993) Effects of weight and body mass index on bone mineral density in men and women: the Framingham study. J Bone Miner Res 8: 567-573.
8. Linli Yuan, Meilian Chang, Jing Wang (2021) Abdominal obesity, body mass index and the risk of frailty in community-dwelling older adults: a systematic review and meta-analysis, Age and Ageing 50(4): 1118-1128.
9. Li B, Li Y, Zhang Y, Liu P, Song Y, et al. (2022) Visceral Fat Obesity Correlates with Frailty in Middle-Aged and Older Adults. Diabetes Metab Syndr Obes 15: 2877-2884.
10. Schrager MA, E Jeffrey Metter, Eleanor Simonsick, Alessandro Ble, Stefania Bandinelli, et al. (2007) Sarcopenic obesity and inflammation in the InCHIANTI study. J Appl Physiol 102: 919-925.This is an epidemiological study that shows that obesity directly affects inflammation and negatively affects muscle strength.
11. Forsythe LK, Wallace JM (2008) Livingstone MB Obesity and inflammation: the effects of weight loss. Nutr Res Rev 21: 117-133.
12. Park HS, Park JY, Yu R (2005) Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-alpha and IL-6. Diabetes Res Clin Pract 69: 29-35.
13. Carnio S, Francesca LoVerso, Martin Andres Baraibar, Emanuela Longa, Muzamil Majid Khan, et al. (2014) Autophagy impairment in muscle induces neuromuscular junction degeneration and precocious aging. Cell Rep 8: 1509-1521.
14. (2003) Marcell TJ Sarcopenia: causes, consequences, and preventions. J Gerontol A Biol Sci Med Sci 58: M911–M916.
15. Cartwright MJ, Tchkonia T, Kirkland JL (2007) Aging in adipocytes: potential impact of inherent, depot-specific mechanisms. Exp. Gerontol 42: 463-471.
16. Shulman GI (2014) Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med 371: 1131–1141.
17. Sepe A, Tchkonia T, Thomou T, Zamboni M, Kirkland JL (2011) Aging and regional differences in fat cell progenitors a mini-review. Gerontology 57: 66-75
18. Kalinkovich A , Livshits G (2017) Sarcopenic obesity or obese sarcopenia: a cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis. Ageing Res Rev 35: 200-221.
19. Aon MA, Bhatt N, Cortassa SC (2014) Mitochondrial and cellular mechanisms for managing lipid excess. Front Physiol 5: 282.
20. Barzilay JI, Blaum   C, Moore   T, Qian Li Xue, Calvin H Hirsch, et al. (2007) Insulin resistance and inflammation as precursors of frailty: the cardiovascular health study. Arch Intern Med 167: 635-641.
21. Xu W, Subashan Perera, Donna Medich, Gail Fiorito, Julie Wagner, et al. (2011) Height loss, vertebral fractures, and the misclassification of osteoporosis. Bone 48: 307-311.
22. Shuster A, Patlas M, Pinthus JH, Mourtzakis M (2012) The clinical importance of visceral adiposity: a critical review of methods for visceral adipose tissue analysis. Br J Radiol 85(1009): 1–10.
23. Garcia Esquinas E, Jose Garcia Garcia   F, Leon Munoz   LM, José Antonio Carnicero, Pilar Guallar Castillón, et al. 2015) Obesity, fat distribution, and risk of frailty in two population-based cohorts of older adults in Spain. Obesity 23: 847-855.
24. Afonso C, Sousa Santos AR, Santos A, Borges N, Padrão P, et al. (2021) Frailty status is related to general and abdominal obesity in older adults. Nutr Res 85: 21-30.
25. Liu CJ (2009) Latham NK Progressive resistance strength training for improving physical function in older adults. Cochrane Database Syst Rev (3): CD0027599.
26. Villareal DT, Lina Aguirre, A Burke Gurney, Debra L Waters, David R Sinacore, et al. (2017) Aerobic or resistance exercise, or both in dieting obese older adults. N Engl J Med 376: 1943-1955.
27. Li B, Li Y, Zhang Y, Liu P, Song Y, et al. (2022) Visceral Fat Obesity Correlates with Frailty in Middle-Aged and Older Adults. Diabetes Metab Syndr Obes 15: 2877-2884.