Paper - Review

DOI: 10.1038/s41591-020-01182-9

Abstract

Integrated
← (1⃣ ubiquity 2⃣ mass 3⃣ lifespan) ← of (all major cell types)
→ to achieve (a comprehensive quantitative description ← of cellular turnover)

Found → (a total cellular mass)
→ turnover of (80 ± 20 grams) per day
← dominated ← by 1⃣ blood cells 2⃣ gut epithelial cells

Contents

Major interest
→ to quantify → (its cellular 1⃣ composition 2⃣ turnover)

Estimated (the number of cells)
← in the adult body
→ which 90% are from the hematopoietic lineage
∵ rigorous census

No corresponding overall census
← of the dynamics of (1⃣ death 2⃣ regeneration of cells & tissues)

Fill → (this knowledge gap)
← concerning (overall cellular turnover dynamics ← of the human body)
← by (1⃣ surveying → the variation in life span 2⃣ quantifying → the cellular turnover rates)

Adopted → the standard reference person

Added → the qualification "healthy" → to the standard reference
∵ the cell turnover rate → may change
∵ different illnesses

Cellular turnover rates
→ vary ← among people
← based on 1⃣ sex 2⃣ age 3⃣ state of health 4⃣ many other facts

The scarcity of (comprehensive data)
→ limits the ability → to perform → a similar holistic analysis
→ remains → to be conducted in future work

The lifespan of cell
→ varies ← across (cell type & tissue)

Define
→ the daily cellular turnover rate
← as the average daily number of cell deaths
← in a specific cell population

❗: continuous recycling of (intracellular components)
← which important for 1⃣ cellular maintenance 2⃣ the overall energetic flux (← of the body)
→ does NOT lead to (cell death)
∴ (Intracellular components) → is NOT a case of (cellular turnover)

1⃣ Cell death 2⃣ Cell production
→ yield → a simple relation ← between the number of cells
→ β = n/𝜏

The daily cellular turnover rate
← is affected by 2 factors
← 1⃣ the number of cells 2⃣ their mean lifespan

A given cell population
→ will contribute
→ to the overall cellular turnover rate
← if it is both 1⃣ numerous 2⃣ possesses → a relative short lifespan

Analyzed → many of the tissues
→ to make (a negligible contribution) ← in both 1⃣ number 2⃣ mass

For each of these cell types
← e.g. 1⃣ sperm cells 2⃣ kidney cells 3⃣ osteocytes
→ 1⃣ the number of cells 2⃣ their mean lifespan

The ratio
← between (these two parameters)
→ gives → the overall daily cellular turnover rate

Map
→ their contribution
→ to the overall daily turnover rates
← by summing the daily cellular turnover rates

The cellular turnover time
→ is defined based
← on cell death
← ❌ cell differentiation

Found
→ that (the total turnover rate ← of the human body)
→ 0.33 X 10^12 cells / day

The three major contributors
→ to the cellular turnover of the human body
→ for about 96% of the total turnover
→ e.g. 1⃣ erythrocytes 2⃣ neutrophils 3⃣ intestinal epithelia

Define
→ the cellular mass turnover rate
← as the mean total mass of cells ← from a specific cell population

This definition
→ addresses → only the replacement of whole cells
← ❌ the intra-cellular turnover

This definition
→ doest NOT → the change in mass
← which involved in the growth of existing cells

∴ This definition
→ only concerned ← with the balance
← between 1⃣ the mass of cell ← that die 2⃣ those replacing them

∴ The cellular turnover rates
→ calculated
← with the man mass of (different cell types)

The total turnover rate ← of human cellular mass
→ is 80 g/day

Blood cells
→ account for only 40% ← of the total cellular mass turnover
∵ their relatively low cellular masses

The epithelial cells
← of the gastro-intestinal tract
→ contribute → about 40% of the cellular mass
∵ 1⃣ their grate single cell unit mass 2⃣ short lifespan

1⃣ Adipocytes 2⃣ muscle cells
→ contribute only around 5%
← to the total mass turnover
∵ their exceptionally long lifespans

Not ❌ locate
→ reliable turnover rates
→ for some cell types

Derive
→ an upper bound
← based on lifespan estimates from rodents

Found
→ an upper bound
→ for the additional total turnover rates
∵ Summing over → all potentially relevant cell types
∵ 1⃣ lung cells 2⃣ hepatocytes

❓: How do the above (human cell turnover rates) compare?
← with those of the bacteria inhabiting our body

The vast majority of human-associated bacteria
→ reside ← in the colon
→ weigh ← in total 200g

Bacteria doubling times
→ are hard to measure
← in the natural gut environment

Infer → the production of 10^14 bacterial cells
→ equal to 1000 g/day

The calculated mass → may be an overestimates
∵ this approach relies ← on measurement ← taken from stool samples

∴ The calculation
→ may NOT adequately represent
→ the total population of the colon

Infer
← an extreme lower bound of (total daily turnover)
← 1⃣ reflecting → the bacteria in the stool 2⃣ assuming → no bacterial cell turnover in the gut

∴ The mass of bacteria
← produced in the body per day
→ is at least ← in the order of magnitude of the produced mass of all human cells
← combined during the same period of time

The difference ← in timescales
→ arises
∵ most of the turnover → occurs in small-to-medium cells

Not all parts (← of the human body)
→ are ever replaced
∴ complete turnover never happens

Provide
→ a comprehensive quantitative description
← in 1⃣ the human body 2⃣ its distribution across cell types

Medical conditions
→ could affect the turnover

Cell turnover
→ is directly linked → to cancer
The cell turnover
← within a tumor
→ may be much faster

The rate of homeostatic (cellular mass turnover)
→ is much higher
← than the rate of (mass accumulation) → for infants
∵ Regarding → the overall turnover of (cellular mass)

The production (← of new cells)
→ is only one of (several mass fluxes)
← in the body

Much of (the normal homeostatic metabolic flux)
→ occurs ← in non-dividing cells

The distinction
← between 1⃣ cellular turnover 2⃣ metabolic flux
← within (existing cells)
→ can sometimes be subtle

The topic of (organism renewal)
← in 1⃣ health 2⃣ disease
→ can be informed by the analysis

❓: how does (the turnover of tumor cells) compare?
→ to the total cellular turnover of patient's body

---